72 results on '"G Cipollini"'
Search Results
2. Reconstructing the Genealogy of a BRCA1 Founder Mutation by Phylogenetic Analysis
- Author
-
G Cipollini, Emma D'Andrea, Fabio Marroni, Generoso Bevilacqua, Ma Caligo, Bernard Peissel, Silvano Presciuttini, Matilde Pensabene, and Paolo Radice
- Subjects
Genetics ,Most recent common ancestor ,Heterozygote ,Time Factors ,Models, Genetic ,Phylogenetic tree ,BRCA1 Protein ,Haplotype ,Population genetics ,Pedigree chart ,Biology ,Founder Effect ,Pedigree ,Haplotypes ,Genetic ,Models ,Mutation ,Mutation (genetic algorithm) ,genetics, Founder Effect, Haplotypes, Heterozygote, Humans, Models ,Genetic, Mutation ,genetics, Pedigree, Phylogeny, Time Factors ,Humans ,Allele frequency ,Phylogeny ,Genetics (clinical) ,Founder effect - Abstract
Estimating the age of founder mutations may contribute to improve our knowledge of population genetics and evolutionary history of diseases. Previous haplotype analysis suggested that the BRCA1*1499insA mutation was a founder allele, probably originated in Tuscany (Italy). Here, we collected additional pedigrees carrying this mutation, and applied a phylogenetic method for estimating mutation age. A chromosome segment of about 25 cM, including 37 short tandem repeats (STRs) on both sides of the BRCA1 gene (DeCode map), was typed in 50 subjects (28 mutation carriers) from 14 unrelated families. The time to the most recent common ancestor (MRCA) of the mutation carriers was estimated by the length of the shared haplotype between all possible pairs of individuals. A function relating the length of the shared haplotype to the time to the MRCA was obtained by a computer simulation. This approach gives results comparable with those of other existing mutation-dating methods, but does not depend explicitly on population-specific parameters such as allele frequencies, provides narrower confidence intervals (CI), and allows one to build an extended genealogical tree of all mutation carriers. The 1499insA mutation shared by the investigated subjects was estimated to be present in an individual living about 30 generations ago (95% CL 22-56), or 750 years (95% CL 550-1,400).
- Published
- 2008
3. RNA-based analysis of BRCA1 and BRCA2 gene alterations
- Author
-
Elisa Sensi, Generoso Bevilacqua, G Cipollini, Paolo Aretini, Grazia Lombardi, Maria A. Caligo, Fabrizia Bonatti, Mariella Tancredi, Chiara Pepe, and Elisabetta Falaschi
- Subjects
Male ,Cancer Research ,endocrine system diseases ,RNA Splicing ,DNA Mutational Analysis ,Genes, BRCA2 ,Genes, BRCA1 ,Breast Neoplasms ,Biology ,Frameshift mutation ,Exon ,Germline mutation ,Genetics ,Humans ,RNA, Messenger ,skin and connective tissue diseases ,neoplasms ,Molecular Biology ,Gene ,Germ-Line Mutation ,Ovarian Neoplasms ,Messenger RNA ,Base Sequence ,Alternative splicing ,RNA ,Sequence Analysis, DNA ,female genital diseases and pregnancy complications ,Pedigree ,Alternative Splicing ,RNA splicing ,Female ,RNA Splice Sites ,Software - Abstract
Alterations in BRCA1 and BRCA2 genes account for a large proportion of hereditary breast and ovarian cancers. Mutations and variants of unknown pathological significance have been identified in both genes; however, most of them have been studied only at the genomic level, and their effect on mRNA expression remains unknown. We identified two BRCA1 and six BRCA2 splice site variants, and one BRCA2 alteration at exon 14. Our aim was to ascertain the effect on RNA processing of the variants still unclassified. We found that BRCA1 c.IVS11 + 1G>A, BRCA2 c.7252_7272delinsTG, BRCA2 c.IVS2 + 1G>A, BRCA2 c.IVS13-2A>G, BRCA2 c.IVS21 + 4A>G, and BRCA2 c.9345G>A lead to aberrant transcripts in lymphocytes. Five of these six splice site variants caused a complete inactivation of the mutant allele because they produced frameshift similar to previously described deleterious exonic variants. Therefore, we consider them to be true deleterious mutations, possibly associated with an increased lifetime risk of breast or ovarian cancer. BRCA1 c.IVS17 + 6C>G, BRCA2 c.IVS12-9del4, and BRCA2 IVS1-9del3 represent rare variants, not disrupting normal mRNA processing. The last two BRCA2 genetic variants had not been reported in the Breast Cancer Information Core BIC database.
- Published
- 2006
4. Papillary lesions of the breast: a molecular progression?
- Author
-
Generoso Bevilacqua, Andrea Cavazzana, Claudio Di Cristofano, G Bertacca, Kaled Ben Romdhane, Karima Mrad, G Cipollini, Paolo Aretini, and Katia Zavaglia
- Subjects
p53 ,Cancer Research ,Pathology ,medicine.medical_specialty ,Loss of Heterozygosity ,Breast Neoplasms ,Locus (genetics) ,Biology ,medicine.disease_cause ,Statistics, Nonparametric ,Malignant transformation ,Papilloma, Intraductal ,Lesion ,Breast cancer ,Chromosome 16 ,Biomarkers, Tumor ,medicine ,Carcinoma ,Humans ,molecular ,16p ,Carcinoma, Ductal, Breast ,16q ,Genes, p53 ,medicine.disease ,Carcinoma, Papillary ,breast papillary cancer ,Carcinoma, Intraductal, Noninfiltrating ,Cell Transformation, Neoplastic ,Oncology ,Papilloma ,Female ,medicine.symptom ,Carcinogenesis ,Chromosomes, Human, Pair 16 ,Gene Deletion - Abstract
Introduction. Breast papillary lesions represent a heterogeneous group of tumors ranging from benign to malignant, including several intermediate forms. Malignant papillary tumors are rare and their molecular characterization is still limited. A few studies pointed to the presence of specific genetic alterations that could be relevant both for diagnostic purposes and to elucidate tumour development and progression. In order to look into the issue, we compared LOH relative frequencies of four microsatellite markers located on chromosome 16 in a set of morphologically different papillary breast lesions. LOH at TP53 locus was also analyzed throughout lesions. Materials and methods. Fifteen cases were analyzed. Sections including a malignant papillary lesion, a benign lesion (when available), and normal breast tissue were selected. Fifteen malignant and twelve benign areas were microdissected using the Leica laser microdissection system (AS LMD). After DNA extraction samples were tested for the following markers: TP53, D16S423, D16S310, DS163210 and D16S476, and analyzed on ABI PRISM 3100 (Applied Biosystems, Foster city CA). Results. Fourteen malignant lesions and twelve paired benign areas appeared to be informative for at least one of the four markers on chromosome 16. In particular, LOH at loci 16p13 and 16q21 was detected in both benign and malignant lesions, whereas LOH at locus 16q23 was limited to malignant lesions. Nine malignant and seven benign lesions were informative for LOH at TP53 locus, that was found to be significantly associated (p=0.01) with the malignant phenotype. Conclusions. Our data suggest an involvement of chromosome 16 mutations in the early steps of breast papillary tumorigenesis. TP53 deletion and possibly LOH at 16q23 appear to play a role as progression factors, being they significantly associated with malignant transformation of breast papilloma.
- Published
- 2005
5. Different Expressivity of BRCA1 and BRCA2: Analysis of 179 Italian Pedigrees with Identified Mutation
- Author
-
Chiara Menin, Simona Agata, Luigi Chieco-Bianchi, Paolo Radice, G Cipollini, Laura Cortesi, Emma D'Andrea, Paolo Marchetti, Lara Della Puppa, Cristina D'Amico, Massimo Federico, Barbara Pasini, Valeria Pensotti, R. Bisegna, Silvano Presciuttini, Generoso Bevilacqua, Renato Mariani Costantini, Laura Ottini, Manuela Santarosa, M. Montagna, Sergio Ferrari, Corrado Ficorella, Davide Iandolo, Arcangela De Nicolo, C Ghimenti, Vittorio Silingardi, Paolo Aretini, Clelia de Giacomi, Daniela Turchetti, Siranoush Manoukian, Maria A. Caligo, Marco A. Pierotti, Enrico Ricevuto, Rosella Crucianelli, Fabio Marroni, Mauro Boiocchi, and Alessandra Viel
- Subjects
Male ,Oncology ,Proband ,Cancer Research ,medicine.medical_specialty ,Genotype ,endocrine system diseases ,allelic heterogeneity - BRCA1 - BRCA2 - expressivity - hereditary breast/ovarian cancer - pedigree analysis ,Genes, BRCA2 ,Genes, BRCA1 ,Breast Neoplasms ,cancer risk ,Biology ,Breast cancer ,Germline mutation ,Risk Factors ,Internal medicine ,Pancreatic cancer ,medicine ,Humans ,BRCA1 ,BRCA2 ,genetics ,Genetic Predisposition to Disease ,skin and connective tissue diseases ,Germ-Line Mutation ,Genetics ,Neoplastic ,Family aggregation ,medicine.disease ,female genital diseases and pregnancy complications ,Pedigree ,Gene Expression Regulation, Neoplastic ,Phenotype ,Gene Expression Regulation ,Genes ,Italy ,Male breast cancer ,genetics, Female, Gene Expression Regulation ,Neoplastic, Genes ,BRCA1, Genes ,BRCA2, Genetic Predisposition to Disease, Genotype, Germ-Line Mutation, Humans, Italy, Male, Pedigree, Phenotype, Regression Analysis, Risk Factors ,Regression Analysis ,Female ,Allelic heterogeneity ,Ovarian cancer - Abstract
Mutations in BRCA1 and BRCA2 show different expressivity with respect to cancer risk, and allelic heterogeneity may be present in both genes. We collected 179 pedigrees with identified germline mutation (104 BRCA1 and 75 BRCA2), ascertained in six collaborating centers of the Italian Consortium for Hereditary Breast and Ovarian Cancer. Significant heterogeneity was detected for several variables, and a logistic regression model including age of diagnosis in the proband, presence of ovarian cancer in the family, presence of prostate or pancreatic cancer in the family, and presence of male breast cancer in the family proved to be effective in predicting the presence of a mutation in a gene rather than the other. Excess of familial aggregation of both breast and ovarian cancer was observed in both genes. Proportion of ovarian cancer was increased in the 5' portion of BRCA1, and presence of prostate or pancreatic cancer in a family was correlated with presence of ovarian cancer in BRCA2.
- Published
- 2003
6. P04.11GENETIC POLYMORPHISMS OF EGF 5'-UTR IN PATIENTS WITH GLIOMA: A POSSIBLE PREDICTIVE MARKER OF OUTCOME
- Author
-
G. Cipollini, I. Florio, Claudio Graiff, Cristina Dealis, G. Di meglio, and Emanuela Vattemi
- Subjects
Cancer Research ,Pathology ,medicine.medical_specialty ,Predictive marker ,Astrocytoma ,Single-nucleotide polymorphism ,Biology ,medicine.disease ,nervous system diseases ,Poster Presentations ,Oncology ,Glioma ,Genotype ,Cancer research ,medicine ,Neurology (clinical) ,Oligodendroglioma ,Allele ,Allele frequency ,neoplasms - Abstract
BACKGROUND: Epidermal growth factor (EGF) plays an important role in carcinogenesis. An adenine (A) to guanine (G) single nucleotide polymorphism at position 61 in the 5'-untranslated region (5'-UTR) of the EGF gene has been found to be associated with levels of EGF production and contribute to the risk of glioma. However, published data are contradictory. EGF +61G/A polymorphism may contribute to the risk of glioma in different ethnic group. Patients with glioma and GG genotype have been reported to have a risk of poorer outcome than patients with AA genotype. Purpose of this study is to investigate the potential role of this polymorphism in cancer progression and its role as predictive marker of outcome in glioma caucasian patients. METHODS: The significant SNP rs4444903, EGF 61A/G, was analyzed in glioma patients and was determined by means of Polymerase Chain Reaction and Direct Sequencing method from blood samples. Association of this genetic polymorphism with clinical and pathological data of patients was evaluated. RESULTS: We investigated EGF +61G/A polymorphism in 28 glioma patients. EGF +61G allele has been found in 68% of glioma patients (22% G/G genotype and 46% A/G genotype). In astrocytomas, EGF +61G allele represents a 83% frequency; in glioblastomas and in oligodendrogliomas, EGF +61G allele frequency represents respectively 73% and 54%. In WHO IV gliomas, the EGF +61G allele represents a 72% frequency, (27% G/G and 45% A/G ), in WHO III gliomas a 81% frequency (54% G/G and 27% A/G ) and in WHO II gliomas a 33% frequency (80% A/G ). Median PFS of glioblastoma patients was 9 months. 79% of glioblastoma patients with a relapsing disease showed the G/G and A/G genotype. No difference was detected in the others histotypes. CONCLUSIONS: Our data confirm previous studies which reported G allele as a risk factor for glioma in Caucasian. G/A and G/G genotypes seem to be more rappresentative in high grade gliomas . Despite limited number of patients, our study supports the predictive role of EGF 61 A/G polymorphism in GBM. Additional large studies are warranted to confirm the role of EGF polymorphism as indipendent prognostic factor in glioma.
- Published
- 2014
7. Neue Erkenntnisse zur fr\xfchmittelalterlichen Adelsgrablege von Niederst\xf6tzingen, Kreis Heidenheim
- Author
-
Wahl, J, G Cipollini, M Francken, K Harvati-Papatheodorou, M-R Kim, F Maixner, N Oxb4Sullivan, T D Price, D Quast, and N Speith & A Zink
- Published
- 2014
8. Down-regulation of thenm23.h1 gene inhibits cell proliferation
- Author
-
Fulvio Basolo, Generoso Bevilacqua, Lisa Fiore, G Merlo, G Rainaldi, Ma Caligo, Andrea Berti, and G Cipollini
- Subjects
Cancer Research ,Messenger RNA ,Metastasis Suppressor Gene ,Oncology ,Downregulation and upregulation ,Oligonucleotide ,Cell growth ,Cellular differentiation ,Transfection ,Biology ,Molecular biology ,Gene - Abstract
nm23 gene expression is strictly related to the state of cell growth. The level of its expression parallels the fraction of thymidine-incorporating cells (S-phase cells) in neoplastic mammary tissues and in the synchronously cycling fraction of MCF10A cells. nm23.h1 reaches a peak of expression in the S-phase, and is present at very low level during the G0/G1 phase. Two strategies are used to demonstrate the direct involvement of the nm23.h1 gene in the process of cell proliferation. The first consists of transient inhibition of nm23.h1 expression by using anti-sense oligonucleotide treatment; weak inhibitory effect on cell proliferation is observed. The second strategy involves the stable inhibition of nm23.h1 expression by transfection of MCF10A cells with a plasmid vector expressing the human nm23.h1 anti-sense mRNA. The anti-sense-transfected cells show consistently slower proliferative activity than the control. Int. J. Cancer 73:297–302, 1997. © 1997 Wiley-Liss, Inc.
- Published
- 1997
9. Switching to floating exchange rates, devaluations, and stock returns in MENA countries
- Author
-
Chortareas, G. Cipollini, A. Eissa, M.A.
- Abstract
We test for the impact of the announcements of floating and/or devaluating the exchange rate on stock returns in three MENA countries after the financial crises they experienced. We, first, use an event-study methodology to test for event-induced abnormal volatility of stock returns in Egypt, Morocco and Turkey. We, then, use three different methodologies to test for abnormal returns: a traditional approach and two approaches that control for event-induced volatility. We find clear evidence of abnormal volatility and abnormal returns due to the floating of the Egyptian and Turkish exchange rates in 2003 and 2001, respectively. In contrast, our results do not show that the devaluation of the Moroccan currency in 2001 resulted in abnormal volatility and/or abnormal returns. © 2011 Elsevier Inc.
- Published
- 2012
10. A low NM23.H1 gene expression identifying high malignancy human melanomas
- Author
-
Generoso Bevilacqua, G. Del Porto, Paola Grammatico, G Cipollini, Ma Caligo, and L. Varesco
- Subjects
Genetic Markers ,Cancer Research ,Skin Neoplasms ,Cell ,Gene Expression ,Dermatology ,Biology ,Cell morphology ,Malignancy ,Disease-Free Survival ,Cell Line ,Lymphocytes, Tumor-Infiltrating ,Predictive Value of Tests ,Gene expression ,Tumor Cells, Cultured ,medicine ,Humans ,Genes, Tumor Suppressor ,Melanoma ,Gene ,Monomeric GTP-Binding Proteins ,Neoplasm Staging ,Chromosome Aberrations ,Karyotype ,NM23 Nucleoside Diphosphate Kinases ,Prognosis ,medicine.disease ,medicine.anatomical_structure ,Oncology ,Cell culture ,Karyotyping ,Nucleoside-Diphosphate Kinase ,Cancer research ,Follow-Up Studies ,Transcription Factors - Abstract
The NM23 gene has been proposed as a metastasis-suppressor gene, and its use has been suggested as prognostic factor. NM23 was identified in a system of murine melanoma cell lines, in which an inverse relationship was found between NM23 expression and metastatic ability. In a human malignant melanoma study NM23 expression was found to be significantly lower in metastases that developed less than 24 months after diagnosis of the primary tumours. The present paper studies the expression of the NM23.H1 gene in cell lines which derive from primary or metastatic human malignant melanomas in relation to staging, infiltration degree, lymphocytic infiltration, cell morphology, cell pigmentation, karyotype, and disease-free survival. The level of mRNA expression of the NM23 gene is significantly lower in cell lines that derive from more infiltrating primary melanomas than in cell lines obtained from less infiltrating tumours. Moreover, cell lines derived from tumours of patients with a disease-free survival of more than 24 months (24-58 months) express the NM23 gene at higher levels than cell lines obtained from melanomas of patients with a disease-free survival of less than 24 months (6-15 months).
- Published
- 1994
11. The progestin ORG2058 but not retinoic acid stimulates BRCA1 mRNA expression in MCF-7 human breast cancer cells
- Author
-
G Cipollini, Ma Caligo, Generoso Bevilacqua, Vincenzo Castronovo, and A Bellachene
- Subjects
Cancer Research ,endocrine system diseases ,medicine.drug_class ,Retinoic acid ,Cancer ,Biology ,medicine.disease ,medicine.disease_cause ,chemistry.chemical_compound ,Progesterone Receptor Positive ,Breast cancer ,Oncology ,chemistry ,MCF-7 ,Estrogen ,Cancer cell ,Cancer research ,medicine ,skin and connective tissue diseases ,Carcinogenesis - Abstract
BRCA1 has been characterized as one of the major breast cancer susceptibility genes. Although no BRCA1 mutations have been reported in sporadic breast cancer, altered levels of BRCA1 are found in non hereditary breast malignant lesions. Therefore, BRCA1 is potentially playing a key role in the genesis of breast cancer. In this study, we explored the effects of estradiol and two differentiating agents, the progestin ORG2058 and retinoic acid, on BRCA1 mRNA expression in human estrogen and progesterone receptor positive MCF-7 cells. Using RNAse protection assay, we have demonstrated that ORG2058 induces a major (50 times) stimulation of BRCA1 mRNA expression. The maximum induction effect was obtained at the pharmacological dose of 100 nM and after 48 h of treatment. While estradiol generated an expected increase of BRCA1 mRNA, retinoic acid did not produce any effects. Our results demonstrate for the first time that BRCA1 is specifically up-regulated by a progestin, a steroid known to induce the differentiation of epithelial mammary cells. The absence of retinoic acid effect suggests that a specific progesterone-dependent pathway, could control BRCA1 expression.
- Published
- 2011
12. Exchange Rates and Stock Prices in the MENA Countries: What Role for Oil?
- Author
-
Chortareas, G. Cipollini, A. Eissa, M.A.
- Abstract
This paper considers the linkage between stock prices and exchange rates in four MENA (Middle East and North Africa) emerging markets. In contrast to the existing evidence that uses a global market index to uncover such a relationship it is found that for the sample countries oil prices emerge as the dominant factor in the above relationship. The paper considers the presence of regime shifts and evidence is found of cointegration only for the period following the 1999 oil price shock. Readjustment towards equilibrium in each stock market occurs via oil price changes. Finally, a number of robustness checks are performed and persistence profiles produced. © 2011 Blackwell Publishing Ltd.
- Published
- 2011
13. Stock returns and exchange rate volatility spillovers in the mena region
- Author
-
Eissa, M.A. Chortareas, G. Cipollini, A.
- Abstract
In this article, we examine the presence of volatility spillovers between nominal exchange rates and stock returns in three MENA countries: Egypt, Morocco and Turkey. The multivariate GARCH model we use does not produce evidence of cross-market effects for the general stock indices returns. Nevertheless, bidirectional shock and volatility spillovers between exchange rates and stock returns exist at the industry sector level. These findings are more pronounced in Egypt and Turkey. The different results are due to the different exchange rate regimes/policies adopted by the three countries. While exchange rates in Egypt and Turkey were allowed to float, Morocco followed a more tightly managed exchange rate regime.
- Published
- 2010
14. Scientific Proceedings Second International Symposium on Cytostatic Drug Resistance
- Author
-
Bridget T. Hill, L. K. Hosking, S. McClean, S. A. Shellard, W. C. M. Dempke, R. D. H. Whelan, M. Sehested, E. Friche, E. J. F. Demant, P. B. Jensen, B. P. Kopnin, B. Wolf, A. Seidel, M. Nickelsen, I. Brandt, G. Heinemann, M. Dietel, S. Bremer, T. Hoof, B. Tümmler, H. J. Broxterman, C. H. M. Versantvoort, C. M. Kuiper, N. Feller, G. J. Schuurhuis, J. Lankelma, S. Gupta, T. Tsuruo, C. Kim, S. Gollapudi, A. Bittl, M. Nap, W. Jäger, B. Lathan, N. Lang, N. T. Raikhlin, A. G. Perevozchikov, J. L. Volodina, T. Licht, H. H. Fiebig, K. J. Bross, F. Herrmann, R. Mertelsmann, I. Bashir, K. Sikora, C. S. Foster, M. Castagna, P. Viacava, M. Cianfrigliao, A. Favati, P. Collecchi, M. A. Caligo, G. Cipollini, G. Bevilacqua, D. Schrenk, T. W. Gant, J. A. Silverman, S. S. Thorgeirsson, A. Harstrick, Z. G. Zhang, H. J. Schmoll, Y. Rustum, M. Mitze, T. Beck, W. Weikel, C. Brumm, P. G. Knapstein, T. McDonald, P. Gardner, N. Kang, S. A. M. van der Heyden, H. J. Elst, U. Stein, B. Jandrig, H. Krause, P. Schmidt-Peter, J. Frege, V. Wunderlich, E. Boven, C. K. van Kalken, H. M. Pinedo, W. Gebauer, E. Fallgren-Gebauer, M. Diete, T. Wagner, M. R. Müller, K. Lennartz, H. R. Nowrousian, S. Seeber, A. A. Shtil, A. R. Kazarov, A. V. Gudkov, A. A. Stavrovskaya, F. H. Djuraeva, T. P. Stromskaya, A. Noller, G. Frese, M. Neumann, A. Wilisch, H. Probst, V. Gekeler, R. Handgretinger, H. Schmidt, C. P. Muller, R. Dopfer, T. Klingebiel, D. Niethammer, S. Weger, H. Diddens, E. Daumiller, A. Bunge, R. Lilischkis, A. Salmassi, M. Kopun, H. Scherthan, C. Granzow, I. Leuschner, D. Schmidt, H. Hoffmann, D. Harms, G. V. Scagliotli, E. Leonardo, S. Cappia, G. Esposito, M. Tombesi, M. Cianfriglia, G. V. Esposito, N. Merendino, M. Viora, M. Caserta, E. Tritarelli, E. Rocca, G. Boccoli, P. Samoggia, C. Fossati, U. Testa, C. Peschle, J. L. Darling, S. M. Ashmore, D. C. Peterson, D. G. T. Thomas, R. A. Kramer, R. Stanlunas, T. Summerhayes, T. Lion, R. H. Shoemaker, L. Wu, A. Smythe, M. R. Boyd, W. T. Beck, M. K. Danks, J. S. Wolverton, M. Chen, B. Y. Bugg, D. P. Suttle, C. V. Catapano, D. J. Fernandes, F. Gieseler, F. Boege, R. Erttmann, H. Arps, L. Zwelling, K. Wilms, H. Biersack, G. J. L. Kaspers, R. Pieters, E. Klumper, F. C. de Waal, E. R. van Wering, A. J. P. Veerman, C. A. Schmidt, F. Lorenz, A. Schäfer, A. Kirsch, W. Siegert, D. Huhn, W. E. Simon, G. Siebert, M. Schneider, M. Oettling, A. Reymann, R. Entmann, S. Schmidt, C. Woermann, C. Windmeier, I. Herzig, B. Schaefer, H. J. Heidebrecht, H. H. Wacker, H. Künnemann, Th. H. M. van Heijningen, M. L. Slovak, J. P. A. Baak, K. Steidtmann, A. -M. J. Fichtinger-Schepman, B. I. Hill, K. J. Scanlon, W. J. Zeller, G. Chen, J. A. Gietema, E. G. E de Vries, D.Th Sleijfer, P. H. B. Willemse, H. J. Guchelaar, D. R. A. Uges, P. Aulenbacher, R. Voegeli, N. H. Mulder, C. Skrezek, H. Bertermann, H. Eichholtz-Wirth, R. Born, H. Bier, M. Koch, G. Bernhardt, K. Hählen, H. Reile, C. H. van Zantwijk, T. Görögh, B. Lippert, J. A. Werner, J. E. Eickbohm, G. H. Mickiseh, M. M. Gottesman, I. Pastan, J. Hofmann, A. Wolf, M. Spitaler, G. Bock, H. Grunicke, H. Ponstingl, I. Roth, C. Dörner, G. Looft, G. J. Ossenkoppele, G. L. Scheffer, G. Atassi, A. Pierre, L. Kraus, S. Leonce, G. Regnier, A. Dhainaut, M. Stöhr, C. Rohlff, R. I. Glazer, Y. S. Cho-Chung, V. Höllt, M. Kouba, G. Vogt, H. Allmeier, N. I. Nissen, S. Cros, N. Guilbaud, T. Dunn, M. Berlion, J. P. Bizzari, A. M. Messing, A. Matuschek, I. Mutter, J. C. W. Kiwit, L. Bastian, P. E. Goretzki, A. Frilling, D. Simon, H. D. Röher, A. Reichle, F. Altmayr, J. Rastetter, C. Erbil, G. Jaques, M. Maasberg, K. Havemann, K. Häußermann, H. -J. Heidebrecht, W. Van de Vrie, E. E. O. Gheuens, N. M. C. Durante, E. A. De Bruijn, R. L. Marquet, A. T. Van Oosterom, A. M. M. Eggermont, M. W. Stow, S. E. Vickers, J. R. Warr, E. Roller, M. Eichelbaum, B. Klumpp, J. Krause, K. Schumacher, S. Hörner, A. Laßmann, U. Traugott, E. Schlick, D. Bürkle, BW Futscher, AF List, WS Dalton, E. Ladda, K. Bühl, A. Weimer, C. Eser, K. Hamprecht, K. P. Schalk, C. Jackisch, B. Brandt, M. Blum, F. Louwen, K. Schulz, J. P. Hanker, U. Rüther, A. Schmidt, H. A. G. Müller, C. Nunnensiek, H. Bader, F. Eisenberger, P. Jipp, B. Niethammer, C. Muller, V. Ling, F. Joncourt, S. Redmond, K. Buser, M. Fey, A. Tobler, K. Brunner, A. Gratwohl, T. Cerrry, V. Nuessler, R. Pelka-Fleischer, C. Nerl, B. Beckert, W. Wilmanns, S. Hegewisch-Becker, M. Fliegner, A. Zander, D. K. Hossfeld, J. Blanz, K. Mewes, G. Ehninger, K. -P. Zeller, H. Schuldes, G. Herrmann, W. Boeckmann, R. Schroeder, D. Jonas, K. -H. Zurborn, H. D. Bruhn, L. Uharek, B. Glass, W. Gassmann, H. Loeffler, W. Mueller-Ruohholtz, W. Mueller-Ruchholtz, K. Jaquet, H. Kreipe, J. Felgner, H. J. Radzun, M. R. Parwaresch, EA Kogan, NN Mazurenko, SM Sekamova, H. Wolf, K. Röhe, K. Wilkens, M. Clausen, E. Henze, J. van der Bosch, S. Rüller, M. Schlaak, U. Köhl, D. Schwabe, E. Rohrbach, E. Montag, S. Bauer, J. Cinatl, I. Cinatl, M. Mainke, H. Geiss, B. Kornhuber, H. Juhl, H. Stritzel, H. Kalhoff, W. Schniegel, T. Menke, B. Pröbsting, P. Schulze-Westhoff, J. Boos, J. Weidner, N. Wedemeyer, K. Wiedorn, Y. Ueda, S. Blasius, P. Wuisman, W. Böcker, A. Roessner, B. Dockhorn-Dworniczak, D. Ramm, J. Knebel, W. Sass, M. Aufderheide, and J. Seifert
- Subjects
Cancer Research ,medicine.medical_specialty ,Oncology ,business.industry ,medicine ,General Medicine ,Drug resistance ,Pharmacology ,Intensive care medicine ,business - Published
- 1991
15. Protein kinase C activity in the central nervous system of the leech, Hirudo medicinalis
- Author
-
Mercedes Garcia-Gil, Marcello Brunelli, G. Cipollini, M. Cattani, and Daniele Bottai
- Subjects
MAP kinase kinase kinase ,Physiology ,Cyclin-dependent kinase 2 ,General Medicine ,Biology ,Mitogen-activated protein kinase kinase ,PKC alpha ,Biochemistry ,MAP2K7 ,biology.protein ,Cyclin-dependent kinase 9 ,Protein kinase A ,Molecular Biology ,Protein kinase C - Abstract
1. 1. We have measured protein kinase C (PKC) activity in cytosolic fractions of leech central nervous system. 2. 2. Phosphatidylserine and oleylacetylglycerol enhanced the activity of the enzyme in a dose-dependent manner even in the absence of calcium. 3. 3. Most of the substrates of the calcium-dependent protein kinase are substrates of the PKC. 4. 4. H-7 and polymyxin B inhibited both PKC and Ca 2+ -dependent protein kinase.
- Published
- 1991
16. NM23 gene expression correlates with cell growth rate and S-phase
- Author
-
Mario Petrini, Fortunato Ciardiello, Generoso Bevilacqua, Stefano Pepe, Fulvio Basolo, Maria A. Caligo, Paola Collecchi, Lisa Fiore, Simonetta Calvo, G Cipollini, M. A., Caligo, G., Cipollini, L., Fiore, S., Calvo, F., Basolo, P., Collecchi, F., Ciardiello, Pepe, Stefano, M., Petrini, G. B. e. v. i. l. a. c. q. u., A., Caligo, Ma, Cipollini, G, Fiore, L, Calvo, S, Basolo, F, Collecchi, P, Ciardiello, Fortunato, Pepe, S, Petrini, M, and Bevilacqua, G.
- Subjects
Cancer Research ,Time Factors ,Lymphocyte ,Breast Neoplasms ,Biology ,Cell Line ,S Phase ,chemistry.chemical_compound ,Gene expression ,medicine ,Humans ,MCF 10A cell ,Breast ,Lymphocytes ,Gene ,Transcription factor ,Monomeric GTP-Binding Proteins ,Cell growth ,NM23 Nucleoside Diphosphate Kinases ,Cell cycle ,human PBL ,Molecular biology ,Nucleoside-diphosphate kinase ,medicine.anatomical_structure ,cell proliferation ,human primary infiltrating ductal breast carcinomas ,Gene Expression Regulation ,Oncology ,chemistry ,Nucleoside-Diphosphate Kinase ,Thymidine ,Cell Division ,Transcription Factors ,NM23 - Abstract
Two human NM23 genes have been identified: NM23.H1 and NM23.H2 coding for the A and B subunit of a nucleoside diphosphate kinase (NDPK), respectively. NM23.H1 gene has been proposed as a suppressor of metastatic ability in tumor cells, NM23.H2 is identical to the c-myc transcription factor, PuF. The NM23 coding sequence is strongly preserved through different species. Indirect evidence of various types has been accumulated and seems to support an implication of NM23 in cell proliferation. This report shows that the NM23 gene expression is strictly related to the growth state of the cells. Two different in vitro systems (human peripheral blood lymphocytes and human breast epithelial cell line MCF-10A) and one in vivo (human primary infiltrating ductal breast carcinomas) system have been investigated. The mRNA is present in PHA-stimulated peripheral blood lymphocytes, whereas it is nearly undetectable in their resting counterparts. The level of the NM23 gene expression parallels the fraction of cells incorporating thymidine (S-phase) in neoplastic mammary tissues. In synchronously cycling MCF-10A cells NM23.H1 mRNA reaehes a maximum abundance in the S-phase and is absent or only present at very low levels during G 0 /G 1 phase, whereas NM23.H2 is present in growth- arrested cells but is upregulated following serum growth stimulation
- Published
- 1995
17. Haplotype analysis of BRCA1 gene reveals a new gene rearrangement: characterization of a 19.9 KBP deletion
- Author
-
Paolo Aretini, Generoso Bevilacqua, Elisa Sensi, Maria A. Caligo, G Cipollini, Grazia Lombardi, Silvano Presciuttini, Claudio Di Cristofano, and Mariella Tancredi
- Subjects
Genes, BRCA1 ,Biology ,Exon ,brca1 ,Replication slippage ,Alu Elements ,Genetics ,Humans ,Genetic Testing ,Allele ,Gene ,Genetics (clinical) ,DNA Primers ,Gene Rearrangement ,Reverse Transcriptase Polymerase Chain Reaction ,Point mutation ,Haplotype ,genomic rearrangement ,haplotype analysis ,hereditary breast cancer ,Gene rearrangement ,Exons ,genomic DNA ,Haplotypes ,Gene Deletion - Abstract
Germ-line mutations in the BRCA1 gene cause hereditary predisposition to breast and ovarian cancer. BRCA1 and BRCA2 mutations account for about 40% of high-risk families. Mutation-screening methods generally focus on genomic DNA and are usually PCR based; they enable the detection of sequence alterations such as point mutations and small deletions and insertions. However, they do not allow the detection of partial or entire exon(s) loss, because the presence of the homologous allele results in a positive PCR signal, giving rise to a false-negative result. Identification of unusual haplotypes in patient samples by an expectation maximisation algorithm has recently been suggested as a method for identifying hemizygous regions caused by large intragenic deletions. Using a similar approach, we identified a novel BRCA1 genomic rearrangement in a breast/ovarian cancer family negative at the first mutation screening; we detected a deletion encompassing exons 14–19, probably due to replication slippage between Alu sequences.
- Published
- 2004
18. Clinicopathological significance of GADD45 gene alterations in human familial breast carcinoma
- Author
-
Generoso Bevilacqua, Mariella Tancredi, Maria A. Caligo, A. Giuseppe Naccarato, Elisa Sensi, Paolo Aretini, Paola Collecchi, Paolo Viacava, and G Cipollini
- Subjects
Cancer Research ,Pathology ,medicine.medical_specialty ,DNA damage ,DNA Mutational Analysis ,Loss of Heterozygosity ,Breast Neoplasms ,Locus (genetics) ,Biology ,Loss of heterozygosity ,Breast cancer ,medicine ,Humans ,Genetic Predisposition to Disease ,skin and connective tissue diseases ,Gene ,Carcinoma ,Intracellular Signaling Peptides and Proteins ,Proteins ,medicine.disease ,Immunohistochemistry ,Pedigree ,Oncology ,Cancer research ,Female ,Breast carcinoma ,DNA Damage - Abstract
GADD45 is a DNA damage responsive gene, induced following BRCA1 expression. Mutations at GADD45 might substitute for p53 alterations in hereditary breast tumours characterized by wild-type p53. We analyzed GADD45 alterations in 59 (15 BRCA-associated) familial breast carcinomas. No mutations were found. LOH at GADD45 locus was identified in 19/59 tumours. GADD45 does not appear to be a frequent mutational target in hereditary breast cancer.
- Published
- 2004
19. Genetic alterations in hereditary breast cancer
- Author
-
Francesco Schittulli, Stefania Tommasi, G Cipollini, Elisa Sensi, Mariella Tancredi, Generoso Bevilacqua, Grazia Lombardi, Maria A. Caligo, A. Paradiso, M. Bruno, Fabrizia Bonatti, Paolo Aretini, and Isa Brunetti
- Subjects
Adult ,endocrine system diseases ,Tumor suppressor gene ,Genotype ,DNA repair ,Breast Neoplasms ,Biology ,medicine.disease_cause ,Breast cancer ,medicine ,Humans ,skin and connective tissue diseases ,Alleles ,Genetic testing ,Aged ,Genetics ,Aged, 80 and over ,BRCA2 Protein ,Mutation ,medicine.diagnostic_test ,BRCA1 Protein ,BRCA mutation ,Age Factors ,Cancer ,Hematology ,Middle Aged ,medicine.disease ,Oncology ,Italy ,Cancer research ,Female - Abstract
Genetic linkage studies have led to the identification of highly penetrant genes as the possible cause of inherited cancer risk in many cancer-prone families. Most women with a family history of breast/ ovarian cancer have tumors characterized by alterations in particular genes, mainly BRCA1 and BRCA2, but also CHK2, ATM, STK11 and others. This paper examines the BRCA1 and BRCA2 genes, focusing on the Italian pattern of mutations. The function of these two genes, classified as tumor suppressors, is linked with key metabolic mechanisms such as DNA damage repair, regulation of gene expression and cell cycle control. The pathological BRCA allelic variants may cause alteration of protein function, transcriptional activity and DNA repair; accumulation of the defects leads to widespread chromosome instability that may be directly responsible for cancer formation. In fact, mutations in BRCA1 and BRCA2, conferring a highly increased susceptibility to breast and ovarian cancer, do not lead to cancer by themselves. The current consensus is that these are ‘caretaker’ genes, which, when inactivated, allow other genetic defects to accumulate. The nature of these other molecular events may define the pathway through which BRCA1 and BRCA2 act. The BRCA mutation spectrum is complex, and the significance of most nucleotide alterations is difficult to understand. Moreover, the mutation pattern seems to be related to ethnicity. The Italian Consortium of Hereditary Breast and Ovarian Cancer has reviewed 1758 families; 23% have been found to be carriers of pathogenetic mutations in BRCA1 or BRCA2. Founder mutations have been described in geographically restricted areas of Italy; a regional founder effect has been demonstrated in Italy for the mutations BRCA1 5083del19 and BRCA2 8765delAG, and a probable new founder mutation has been characterized in Tuscany. The presence of founder mutations has practical implications for genetic testing.
- Published
- 2004
20. Penetrances of breast and ovarian cancer in a large series of families tested for BRCA1/2 mutations
- Author
-
Paolo Aretini, Silvano Presciuttini, Laura Cortesi, G Cipollini, Generoso Bevilacqua, Emma D'Andrea, Alessandra Viel, Enrico Ricevuto, Joan E. Bailey-Wilson, Massimo Federico, M. Montagna, Giovanni Parmigiani, Maria A. Caligo, Manuela Santarosa, Fabio Marroni, and Paolo Marchetti
- Subjects
Adult ,Risk ,Oncology ,medicine.medical_specialty ,Genetic counseling ,Genes, BRCA2 ,Genes, BRCA1 ,Adult, Aged, Breast Neoplasms ,epidemiology/genetics, Computer Simulation, Female, Genes ,BRCA1, Genes ,BRCA2, Humans, Likelihood Functions, Middle Aged, Mutation, Ovarian Neoplasms ,epidemiology/genetics, Penetrance, Risk, apping ,Breast Neoplasms ,Penetrance ,Biology ,BRCA1 ,BRCA2 ,penetrance ,genetic testing ,predictive models ,BRCAPRO ,Breast cancer ,Germline mutation ,Internal medicine ,apping ,Genetic model ,Genetics ,medicine ,Humans ,Computer Simulation ,skin and connective tissue diseases ,Genetics (clinical) ,Aged ,Genetic testing ,Ovarian Neoplasms ,Likelihood Functions ,epidemiology/genetics ,medicine.diagnostic_test ,Chromosome Mapping ,Cancer ,Middle Aged ,medicine.disease ,Genes ,Mutation ,Female ,Ovarian cancer - Abstract
Accurate estimates of breast and ovarian cancer penetrance in BRCA1/2 mutation carriers are crucial in genetic counseling. Estimation is difficult because of the low frequency of mutated alleles and the often-uncertain mechanisms of family ascertainment. We estimated the penetrances of breast and ovarian cancers in carriers of BRCA1/2 mutations by maximizing the retrospective likelihood of the genetic model, given the observed test results, in 568 Italian families screened for germline mutations. The software BRCAPRO was used as a probability calculation tool in a Markov Chain Monte Carlo approach. Breast cancer penetrances were 27% (95% CI 20-34%) at age 50 years and 39% (27-52%) at age 70 in BRCA1 carriers, and 26% (0.18-0.34%) at age 50 and 44% (29-58%) at age 70 in BRCA2 carriers, and ovarian cancer penetrances were 14% (7-22%) at age 50 and 43% (21-66%) at age 70 in BRCA1 carriers and 3% (0-7%) at age 50 and 15% (4-26%) at age 70 in BRCA2 carriers. The new model gave a better fit than the current default in BRCAPRO, the likelihood being 70 log units greater; in addition, the observed numbers of mutations in families stratified by gene and by cancer profile were not significantly different from those expected. Our new penetrance functions are appropriate for predicting breast cancer risk, and for determining the probability of carrying BRCA1/2 mutations, in people who are presently referred to genetic counseling in Italy. Our approach could lead to country-customized versions of the BRCAPRO software by providing appropriate population-specific estimates.
- Published
- 2004
21. p53 inactivation is a rare event in familial breast tumors negative for BRCA1 and BRCA2 mutations
- Author
-
Paolo Viacava, G Cipollini, Maria A. Caligo, Mariella Tancredi, Generoso Bevilacqua, Elisa Sensi, Paolo Aretini, and A. Giuseppe Naccarato
- Subjects
Adult ,Male ,Cancer Research ,Pathology ,medicine.medical_specialty ,endocrine system diseases ,Tumor suppressor gene ,Genes, BRCA2 ,Genes, BRCA1 ,Breast Neoplasms ,Biology ,Gene mutation ,Malignancy ,medicine.disease_cause ,Polymerase Chain Reaction ,Breast Neoplasms, Male ,Breast cancer ,Germline mutation ,medicine ,Humans ,Point Mutation ,Neoplastic transformation ,skin and connective tissue diseases ,Germ-Line Mutation ,Polymorphism, Single-Stranded Conformational ,Point mutation ,Middle Aged ,medicine.disease ,Genes, p53 ,Immunohistochemistry ,Gene Expression Regulation, Neoplastic ,Phenotype ,Oncology ,Cancer research ,Female ,Tumor Suppressor Protein p53 ,Carcinogenesis - Abstract
Germline mutations at BRCA1 or BRCA2 genes result in susceptibility to breast and ovarian cancers. BRCA1- and BRCA2-associated tumors have distinct histologic and molecular phenotypes, as compared to sporadic breast tumors. Typically, a higher grade of malignancy is observed in BRCA-associated cancers. A number of studies have suggested that BRCA1 and BRCA2 proteins are of importance in DNA repair and maintenance of genome integrity, bringing about molecular models of tumor pathogenesis. In particular, alterations at p53 gene have been suggested to be a necessary step in the tumorigenesis of BRCA-associated carcinomas. In fact, BRCA-associated breast cancers have higher p53 mutation frequencies than sporadic ones. At present, very little is known regarding BRCA non-associated familial tumors (termed BRCAx tumors). To our knowledge no data is available on p53 alterations in this sub-group of familial tumors. In this study p53 alteration frequencies were evaluated in 13 BRCA1, 11 BRCA2 and 55 BRCAx breast tumors. Tumor samples were analyzed for p53 gene mutations by PCR-SSCP/direct sequencing, and for p53 protein overexpression by immunohistochemistry (IHC). Altogether, p53 alterations were detected in 54% of BRCA1 tumors compared with 5% of BRCAx tumors. No p53 alteration was found in BRCA2 tumors. While loss of p53 checkpoint control is likely to be an important step in the molecular pathogenesis of BRCA1-associated cancers, our data seem to indicate a p53-independent molecular mechanism underlying BRCAx neoplastic transformation.
- Published
- 2003
22. HVDC submarine power cable systems-state of the art and future developments
- Author
-
D. Valenza and G. Cipollini
- Subjects
Engineering ,Interconnection ,Transmission (telecommunications) ,business.industry ,Direct current ,Electrical engineering ,Submarine ,business ,Submarine power cable ,Electrical conductor ,Power (physics) ,Voltage - Abstract
The paper begins with an introduction on the reasons that lead to the use of HVDC submarine cable links. The main aspects for the choice of direct current are presented as well as the advantages deriving from the utilization of submarine cables. The second part is dedicated to a discussion on the various type of insulation that could be used in power cables and their possible application to HVDC submarine cables. There is a description of the main characteristics and technical details of two projects. The first is Spain-Morocco link, a 26 km long interconnection for the transmission, in a first phase, of 700 MW from Spain to Morocco at 400 kV AC by means of three cables, plus one spare, of the fluid filled type. The cables are designed for a future change to 450 kV DC, allowing a transmission of 500 MW each (i.e. 2 GW total). One of the peculiarities of the link is the maximum water depth of 615 m (world record for submarine power cables at the time of installation). The second is the Italy-Greece link, a 160 km long interconnection for the transmission of 500 MW (bi-directional) by means of one paper insulated mass impregnated cable having 1250 mm/sup 2/ conductor size and insulated for a rated voltage of 400 kV. This link will attain the world record for the maximum water depth for submarine power cables: 1000 m. The last part deals with the future development expected in this field, in terms of conductor size and voltage leading to an increase in transmissible capacity.
- Published
- 2002
23. Mutational analysis of the NM23.H1 gene in human breast cancer
- Author
-
Generoso Bevilacqua, G Cipollini, Angela Moretti, Maria A. Caligo, C Ghimenti, and Paolo Viacava
- Subjects
Untranslated region ,Cancer Research ,Point mutation ,DNA Mutational Analysis ,Loss of Heterozygosity ,Single-strand conformation polymorphism ,Breast Neoplasms ,Biology ,Middle Aged ,NM23 Nucleoside Diphosphate Kinases ,Molecular biology ,Stop codon ,Loss of heterozygosity ,Exon ,Nucleoside-Diphosphate Kinase ,Genetics ,Cancer research ,Humans ,RNA, Messenger ,Transversion ,Molecular Biology ,Polymorphism, Single-Stranded Conformational ,Monomeric GTP-Binding Proteins ,Transcription Factors - Abstract
NM23.H1 is a protein connected with tumor progression. Loss of heterozygosity and reduced expression of the gene have been associated with poor prognosis and increased incidence of metastases in many epithelial tumors. The aim of this study was to detect the presence of NM23.H1 point mutations or small deletions in human breast carcinomas by using the single-strand-conformation polymorphism (SSCP) technique. Mutational analysis was performed on 76 breast tumors, 10 of which had allelic deletion of the gene. The NM23.H1 mRNA content also was evaluated in each sample. Only a C-to-A transversion leading to a stop codon was found in the 5' untranslated region of exon 1. A polymorphic SSCP pattern was identified in exon 1; direct sequencing showed a C-to-T transition 30 nucleotides upstream from the 5' splice site flanking exon 1. None of the tumors analyzed presented both alleles inactivated. Our results suggest that NM23.H1 is rarely inactivated by point mutations.
- Published
- 2000
24. Germline mutations of BRCA1-associated RING domain (BARD1) gene in breast and/or ovarian families negative for BRCA1 and 2 alterations
- Author
-
Generoso Bevilacqua, Sergio Ricci, D Iandolo, Elisa Sensi, G Cipollini, Ma Caligo, C Ghimenti, and Pierfranco Conte
- Subjects
Germline mutation ,Breast cancer ,BARD1 Gene ,Surgical oncology ,business.industry ,Cancer research ,medicine ,Ring domain ,medicine.disease ,business ,Bioinformatics - Published
- 2000
25. P53 mutations in breast and ovarian carcinomas from BRCA1 and 2 mutation carriers and noncarriers
- Author
-
G. Naccarato, D Iandolo, Paolo Viacava, Generoso Bevilacqua, Ma Caligo, Elisa Sensi, C Ghimenti, and G Cipollini
- Subjects
Oncology ,Pathology ,medicine.medical_specialty ,Breast cancer ,business.industry ,Surgical oncology ,Internal medicine ,Meeting Abstract ,Mutation (genetic algorithm) ,medicine ,Ovarian carcinomas ,business ,medicine.disease - Published
- 2000
26. Mutation analysis of BRCA1 and BRCA2 in italian hereditary and sporadic forms of breast and ovarian cancer: tumor genotype-phenotype correlation in breast cancer BRCA-mutation carriers
- Author
-
G Cipollini, Elisa Sensi, Ma Caligo, C. Ghimenti, G. Naccarato, D Iandolo, Generoso Bevilacqua, P. Viacava, A. Berti, D. Campani, and A. Piccirilli
- Subjects
Pathology ,medicine.medical_specialty ,Article Subject ,endocrine system diseases ,Clinical Biochemistry ,Exon ,Breast cancer ,Germline mutation ,Genetics ,Medicine ,Neoplasm ,Allele ,skin and connective tissue diseases ,Molecular Biology ,Abstract ,lcsh:R5-920 ,business.industry ,Point mutation ,Biochemistry (medical) ,BRCA mutation ,General Medicine ,medicine.disease ,female genital diseases and pregnancy complications ,Cancer research ,lcsh:Medicine (General) ,business ,Ovarian cancer - Abstract
Predisposition to breast and ovarian cancer has been attributed to mutant BRCA1 alleles in 90% of hereditary combined tumors and in 45% of hereditary breast cases, whereas mutations in BRCA2 gene are thought to account for about 35% of inherited breast cancers. On the other hand, the presence of mutations in the sporadic forms of these tumors is an infrequent event. This suggests that tumors arising in BRCA mutation carriers may differ from BRCA negative hereditary and sporadic cancer in genetic and biological features as well as in clinical behaviour. We undertook our study to evaluate the frequent of BRCA mutations in patients with hereditary and sporadic breast and/or ovarian tumors in order to explore if specific pathological and clinical features of tumors are associated with BRCA1 and BRCA2 mutations. Mutational analysis was also performed for exon 11 by PTT complemented by SSCP for the remaining entire coding region and exon-intron splice boundaries. Direct sequence analysis was used to identify the genetic alterations. DNA germline mutations were detected in 22 out 76 (29%) families; 15 probands (20%) showed BRCA1 mutations; 7 patients (9%) presented mutations in the BRCA2 gene. About 50% (11/22) BRCA-mutations were detected in families with three or more affected relatives most of which (8/11) occurred in BRCA1; 27% (6/22) BRCA-mutations were observed in families with two affected relatives; 18% (4/22) in families with one affected relative and one BRCA-mutation (5%; 1/22) was identified in a borderline family. No hot spot of mutations was found in the two genes, but almost 50% occurred in exon 11 of BRCA1 and BRCA2. The BRCA-mutational analysis, performed on 30 primary early onset breast cancers ( 36 yrs.) and 18 ovarian carcinomas ( 50 yrs.), revealed the presence of: a) one somatic point mutation, an 5382insC, in one ovarian cancer patient, b) a rare sequence variant in exon 15 in one case of breast cancer, c) four different common polymorphisms (one in intron 8 in breast and ovarian tumors, one in intron 7 in breast carcinomas and one in exon 13 and in exon 16 in ovarian neoplasm). The specific pathological and clinical features of breast-tumors associated with BRCA1 and BRCA2 mutations were explored (histological type, pathological grade, lymph node status, tumor size, lymphatic and blood vessel tumor emboli, tumor necrosis, presence of other lesions in the parenchyma collateral to invasive carAbstract
- Published
- 1999
27. Bcl-2, p53 and MIB-1 expression in normal and neoplastic parathyroid tissues
- Author
-
Angelo G. Bonadio, Paolo Miccoli, Antonio Giuseppe Naccarato, Paolo Viacava, Edda Vignali, Claudio Marcocci, G Cipollini, and Luisella Cianferotti
- Subjects
p53 ,Adenoma ,Adult ,Male ,Pathology ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Biology ,medicine.disease_cause ,Parathyroid Glands ,Endocrinology ,Antigen ,medicine ,80 and over ,Humans ,Bcl-2 ,Nuclear ,Antigens ,Parathyroid tumors ,neoplasms ,Aged ,Aged, 80 and over ,Hyperparathyroidism ,Parathyroid neoplasm ,Nuclear Proteins ,Antigens, Nuclear ,MIB-1 ,Normal parathyroid ,DNA-Binding Proteins ,Female ,Immunohistochemistry ,Ki-67 Antigen ,Middle Aged ,Parathyroid Neoplasms ,Proto-Oncogene Proteins c-bcl-2 ,Tumor Suppressor Protein p53 ,medicine.disease ,digestive system diseases ,Diabetes and Metabolism ,Parathyroid carcinoma ,Apoptosis ,Cancer research ,Carcinogenesis - Abstract
An altered control of the mechanisms involved in cell proliferation and programmed cell death (apoptosis) might play an important role in parathyroid tumorigenesis. We evaluated by immunohistochemistry the expression of bcl-2 and p53 proteins, as markers of apoptosis control, and MIB-1, as marker of cell proliferation, in a series of normal and neoplastic parathyroid tissues. The specimens were 33 normal parathyroids, 43 parathyroid adenomas and 3 parathyroid carcinomas. Results were scored as positive when more than 1% of cells were stained for MIB-1 and p53, and more than 10% for bcl-2. All normal parathyroids showed numerous bcl-2 positive cells (> or = 80%), low proliferation rate (MIB-1) and no p53 protein expression. Twenty-four (55%) adenomas were bcl-2 positive; in 16 of these the number of positive cells was high (> 50%) and immunoreactivity was diffusely distributed within the adenoma; 8 cases showed a zonal staining pattern, in which groups of stained cells were surrounded by negative cells. Nineteen adenomas (45%) and all carcinomas were bcl-2 negative. A high proliferative rate (MIB-1) was found in all carcinomas and 4 adenomas (9%); all MIB-1 positive adenomas were bcl-2 negative. p53 was negative in all specimens. No significant differences in serum calcium and intact PTH levels nor in tumor size were found between bcl-2 negative and bcl-2-positive and MIB-1-positive and MIB-1-negative adenomas. An inverse, but not statistically significant (p = 0.06) correlation was observed between the percentage of bcl-2 positive cells and serum calcium level in parathyroid adenomas. In conclusion, parathyroid adenomas are a heterogeneous group of lesions in which the pattern of bcl-2 and MIB-1 protein expression ranges between that of normal parathyroid (bcl-2 positivity and MIB-1 negativity) and that of parathyroid carcinoma (bcl-2 negativity and MIB-1 positivity). The question of whether the finding of the MIB-1 positive-bcl-2 negative phenotype identifies a subgroup of clinically more aggressive adenomas remains to be established.
- Published
- 1998
28. Down-regulation of the nm23.h1 gene inhibits cell proliferation
- Author
-
G, Cipollini, A, Berti, L, Fiore, G, Rainaldi, F, Basolo, G, Merlo, G, Bevilacqua, and M A, Caligo
- Subjects
Down-Regulation ,DNA ,NM23 Nucleoside Diphosphate Kinases ,Oligonucleotides, Antisense ,Transfection ,Epithelium ,Gene Expression Regulation, Enzymologic ,Nucleoside-Diphosphate Kinase ,Humans ,Female ,Breast ,RNA, Messenger ,Cell Division ,Cell Line, Transformed ,Monomeric GTP-Binding Proteins ,Transcription Factors - Abstract
nm23 gene expression is strictly related to the state of cell growth. The level of its expression parallels the fraction of thymidine-incorporating cells (S-phase cells) in neoplastic mammary tissues and in the synchronously cycling fraction of MCF 1OA cells. nm23.h1 reaches a peak of expression in the S-phase, and is present at very low level during the GO/G1 phase. Two strategies are used to demonstrate the direct involvement of the nm23.h1 gene in the process of cell proliferation. The first consists of transient inhibition of nm23.h1 expression by using anti-sense oligonucleotide treatment; weak inhibitory effect on cell proliferation is observed. The second strategy involves the stable inhibition of nm23.h1 expression by transfection of MCF1OA cells with a plasmid vector expressing the human nm23.h1 anti-sense mRNA. The anti-sense-transfected cells show consistently slower proliferative activity than the control.
- Published
- 1997
29. NM23 gene expression in human breast carcinomas: loss of correlation with cell proliferation in the advanced phase of tumor progression
- Author
-
Generoso Bevilacqua, Maria A. Caligo, Paola Collecchi, G Cipollini, Paolo Viacava, and Andrea Berti
- Subjects
Cancer Research ,Pathology ,medicine.medical_specialty ,Axillary lymph nodes ,Transcription, Genetic ,Breast Neoplasms ,Biology ,Metastasis ,Necrosis ,medicine ,Carcinoma ,Biomarkers, Tumor ,Humans ,Neoplasm Invasiveness ,RNA, Messenger ,Neoplasm Metastasis ,Lymph node ,Monomeric GTP-Binding Proteins ,NM23 Nucleoside Diphosphate Kinases ,medicine.disease ,Primary tumor ,Metastasis Suppressor Gene ,medicine.anatomical_structure ,Oncology ,Tumor progression ,Lymphatic Metastasis ,Nucleoside-Diphosphate Kinase ,Cancer cell ,Disease Progression ,Regression Analysis ,Female ,Cell Division ,Transcription Factors - Abstract
NM23 is a protein associated with tumor progression, expressed in all tissues and in human tumors. Reduced expression of NM23.H I is related to high incidence of lymph node and distant metastasis or to poor prognosis of the patient in several human malignant tumors. In this study we analyze NM23 expression in non-neoplastic mammary tissues surrounding the tumoral lesions, in human mammary carcinomas and in lymph node metastasis. Our analysis shows that NM23.H I expression is lower in the mammary cells surrounding the tumor than in the tumor itself. In the primary tumors we observed a negative trend between degree of local invasion and level of NM23.H I expression. A further decrease of NM23.H I was detected in the invasive tumors that metastasized to axillary lymph nodes and in the metastasis. NM23.H2 was always more highly expressed than NM23.H1, and reduced expression of NM23.H1 but not NM23.H2 was concordant with the presence of lymph node metastasis or local invasiveness of the primary tumor. A positive correlation between NM23.H I mRNA content and cell growth rate of breast tumor cells has been confirmed. However, this trend was not maintained in cancer cells from tumors that metastasized to axillary lymph nodes and in metastatic cells; in these 2 situations the NM23.H1 mRNA content varied without any relationship to the proliferative rate of the cells. In addition, in comparison with the initial tumor, the metastatic cell population showed a strong decrease of NM23.H1 expression and increased proliferative activity.
- Published
- 1997
30. Down regulation of NM23.H1, NM23.H2 and c-myc genes during differentiation induced by 1,25 dihydroxyvitamin D3
- Author
-
Mario Petrini, Generoso Bevilacqua, Paola Valentini, Maria A. Caligo, and G Cipollini
- Subjects
Cancer Research ,Cellular differentiation ,Genes, myc ,Down-Regulation ,HL-60 Cells ,Downregulation and upregulation ,Calcitriol ,Transcription (biology) ,Gene expression ,Tumor Cells, Cultured ,Humans ,Gene ,Monomeric GTP-Binding Proteins ,biology ,Cell growth ,Cell Differentiation ,Hematology ,NM23 Nucleoside Diphosphate Kinases ,biology.organism_classification ,Blotting, Northern ,Molecular biology ,Oncology ,Genes ,Cell culture ,Nucleoside-Diphosphate Kinase ,Lymphoma, Large B-Cell, Diffuse ,Drosophila melanogaster ,Cell Division ,Transcription Factors - Abstract
The NM23 gene, involved in the negative regulation of metastatic progression, has been found to be highly homologous to developmentally regulated genes such as the awd gene in Drosophila melanogaster and the Gip17 gene in Dyctiostelium discoideum. To ascertain whether the NM23 genes are involved in the differentiation processes of human cell lines, the NM23.H1 and NM23.H2 expression level has been determined during the monocyte-macrophage differentiation of HL-60 and U-937 cell lines induced by vitamin D3. In both lines, vitamin D3 produced induction of differentiate markers, inhibition of cell proliferation and a decrease of the NM23.H1, NM23.H2 and c-myc genes, behaving both as a differentiative and an antiproliferative agent. The fact that the c-myc transcriptional factor PuF is identical to the NM23.H2 gene and that NM23 protein could be a transcriptional factor suggests that the regulatory action exerted by vitamin D3 on c-myc transcription is mediated by NM23.H2.
- Published
- 1996
31. SPORADIC PANCREATIC DUCTAL CARCINOMA IN PATIENTS AGED LESS THAN 40 YEARS
- Author
-
Angela Michelucci, Andrea Cavazzana, C Di Cristofano, Ugo Boggi, Luca Pollina, Maria A. Caligo, Generoso Bevilacqua, N. Decarli, Paola Collecchi, Daniela Campani, G Cipollini, G Bertacca, N. Funel, M Del Chiaro, Michele Menicagli, and Franco Mosca
- Subjects
medicine.medical_specialty ,Endocrinology ,Hepatology ,business.industry ,Endocrinology, Diabetes and Metabolism ,Internal medicine ,Internal Medicine ,Medicine ,In patient ,Pancreatic carcinoma ,business ,Gastroenterology - Published
- 2004
32. 449 BRCA1 gene mutation carrier analysis in familial breast cancer patients
- Author
-
Sergio Ricci, R. Olsen, G. Bevilacqua, M.A. Caligo, Mark H. Skolnick, Andrea Antonuzzo, G. Cipollini, Pierfranco Conte, C. Ghimenti, Cheryl Frye, M.P. Maresi, V. Marchetti, S. Neuhausen, Donna M Shattuck-Eidens, Giacomo Allegrini, and Melody McClure
- Subjects
Genetics ,Cancer Research ,Biology ,medicine.disease ,Germline ,Frameshift mutation ,Breast cancer ,Germline mutation ,Oncology ,Mutation Carrier ,Genotype ,medicine ,Missense mutation ,skin and connective tissue diseases ,Ovarian cancer - Abstract
BRCA1, the predisposing gene for familial breast and ovarian cancer localized on chromosome 17q21.3 has been recently cloned. The gene comprises 22 coding exons which span 100 kB of genomic sequence. The protein predicted is 1863 aminoacids long. 31 mutations have been identified in constitutional DNA of affected member from various family of which 22 were distinct. Not one of 22 transcribed exons seems to be a preferential target site for mutations. Overall germline BRCA1 mutations account for 1–2% of all breast cancers and about 3% of ovarian cancers. The lifetime risk of breast and ovarian cancer in BRCA1 mutation carriers is high: the risk of breast cancer is about 50% by age 50 and 70% by age 70. The average risk of ovarian cancer is 40% by age 70. BRCA1 has never been found mutated in sporadic carcinomas, however, loss of heterozigosity in the region of BRCA1 has been observed in 40% of breast and about 60% of ovarian cancers. The lifetime risk to develop the familial form of the disease may be calculated by identifying mutations in BRCA1 or BRCA2 genes. From the screening of 1100 medical records of patients subjected to mastectomy in S. Chiara Hospital in Pisa during the period 1990–1994, the patients with a referred familial recurrence of breast or ovarian cancer were selected for interview. 81 patients belonging to 75 families fitted the BRCA1 eligibility criteria. 37 patients belonging to different families were analyzed for BRCA1 germline mutation. All 37 families are Caucasian and principally reside in Tuscany. Mutation screening was done by ASO (allelic specific oligo hybridization) for three common mutations and by direct sequencing of each of the coding exons. The analysis is under way and approximately 50% ofthe coding region has been screened up to now. We have so far identified 7 mutations of which 5 are different. Three are frameshift and 2 missense. Only one of the mutations found has been reported previously (5382insC). The insertion of an A has been reported in three different families, the aplotype analysis has been performed to ascertain if a common ancestor exist for those three families. No evident correlation between phenotype and genotype has been detected. CG and GC are fellows of the Italian Association for Cancer Research. This work was supported by AIRC and CNR PF ACRO grants.
- Published
- 1995
33. Chromosome abnormalities and NM23-H1 expression in human renal carcinoma
- Author
-
S. Rossi, Paolo Simi, A. Caligo, Generoso Bevilacqua, G. Andreani, C. Traino, and G. Cipollini
- Subjects
Cancer Research ,Genetics ,Cancer research ,Chromosome ,Biology ,Molecular Biology ,Renal carcinoma - Published
- 1996
34. BRCA 1 germline mutational spectrum in 21 Italian families
- Author
-
Mark H. Skolnick, G Cipollini, V. Marchetti, D. Shattuck-Eidens, Generoso Bevilacqua, S. Ricci, Isa Brunetti, Pierfranco Conte, Maria A. Caligo, and C Ghimenti
- Subjects
Genetics ,Cancer Research ,Biology ,Molecular Biology ,Germline - Published
- 1996
35. Expression of NM23H1 gene and monosomy of # 22
- Author
-
S. Rossi, Rosario Casalone, A. Caligo, M. Cattani, Paolo Simi, Generoso Bevilacqua, and G. Cipollini
- Subjects
Cancer Research ,Monosomy ,Expression (architecture) ,Genetics ,medicine ,Biology ,medicine.disease ,Molecular Biology ,Gene ,Molecular biology - Published
- 1994
36. cAMP-dependent protein phosphorylation of a 79kDa protein in segmental ganglia of the leech Hirudo medicinalis
- Author
-
Enrico Tongiorgi, Mercedes Garcia-Gil, Marcello Brunelli, G. Cipollini, and M. Cattani
- Subjects
Gel electrophoresis ,Nervous system ,biology ,Nervous tissue ,Central nervous system ,Leech ,Phosphodiesterase ,Cell Biology ,biology.organism_classification ,Cellular and Molecular Neuroscience ,Hirudo medicinalis ,medicine.anatomical_structure ,Biochemistry ,medicine ,Protein phosphorylation - Abstract
Incubation of leech segmental ganglia with [ 32 P]phosphoric acid results in the labeling of 30 phosphoproteins, detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, followed by autoradiography. Treatment with 8-bromo-cAMP or phosphodiesterase inhibitors induces a rise in the label of the following phosphoproteins: 96, 79, 63, 50, 40, 32, 28, 24, 23 and 20 kDa. One of the most intersting membrane-bound proteins studied has an apparent molecular weight of 79 kDa. It seems to be specific for the nervous tissue and inside the nervous system, for segmental ganglia. The role of these phosphoproteins in the mechanisms of learning processes is discussed.
- Published
- 1989
37. Evaluation of widely used models for predicting BRCA1 and BRCA2 mutations
- Author
-
Fabio Marroni, Generoso Bevilacqua, M. Montagna, Silvano Presciuttini, Paolo Aretini, Alessandra Viel, Sergio Ferrari, Enrico Ricevuto, Laura Cortesi, Maria A. Caligo, Manuela Santarosa, G Cipollini, Emma D'Andrea, R. Bisegna, Joan E. Bailey-Wilson, and Giovanni Parmigiani
- Subjects
Adult ,Male ,Proband ,Genetic counseling ,DNA Mutational Analysis ,Genetic Carrier Screening ,Breast Neoplasms ,Context (language use) ,Adult, Breast Neoplasms ,genetics, DNA Mutational Analysis ,methods, Female, Genes ,BRCA1, Genes ,BRCA2, Genetic Testing, Heterozygote Detection ,methods, Humans, Male, Middle Aged, Models ,Genetic, Mutation, Ovarian Neoplasms ,genetics, ROC Curve ,Biology ,Heterozygote Detection ,methods ,symbols.namesake ,Genetic ,Mutation Carrier ,Models ,Genetics ,medicine ,Humans ,Genetic Testing ,Genetics (clinical) ,Genetic testing ,Ovarian Neoplasms ,medicine.diagnostic_test ,Middle Aged ,BRCA1 ,BRCA2 ,BRCA1 and BRCA2 mutations ,Genes ,ROC Curve ,Mutation ,Mutation (genetic algorithm) ,Mendelian inheritance ,symbols ,Female ,Letter to JMG - Abstract
Deleterious mutations of the BRCA1 and BRCA2 genes are a major risk factor for the development of breast and ovarian cancers.1–4 Mutation tests for these two genes commonly are now offered in specialised clinics.5,6 As a result, a large number of women with personal or family histories of breast or ovarian cancer seek genetic counselling. Accurate evaluation of the probability that a woman carries a germline pathogenic mutation at BRCA1 or BRCA2 therefore is essential to help counsellors and those being counselled to decide whether testing is appropriate. In this context, the questions of practical interest are: Given the pedigree, what is the chance of a mutation being present? and What is the chance of the DNA laboratory finding a mutation? After testing became available, several models were developed to assess the pre-test probability of identifying carriers of mutations. Broadly speaking, two different approaches have been used to develop predictive models: the “empirical approach” and the “Mendelian approach”.7 In empirical models, families are stratified according to variables that describe their family history; regression or other approaches are used to predict the results of Mendelian testing. In some cases, this approach simply consists of observing the proportion of mutations found in different strata. Mendelian models, in contrast, address the probability that a proband is a mutation carrier on the basis of explicit assumptions about the genetic parameters (allele frequencies and cancer penetrances in carriers and non-carriers) and the Mendelian rules of gene transmission. A consequence of the two different strategies is that the Mendelian models evaluate the probability that a proband is a gene carrier, whereas the empirical models evaluate the probability of identifying a mutation. The main purpose of this study was to compare the performances of published models in predicting mutation test results in …
38. Microscopic Evidence of Malaria Infection in Visceral Tissue from Medici Family, Italy.
- Author
-
Maixner F, Drescher D, Boccalini G, Piombino-Mascali D, Janko M, Berens-Riha N, Kim BJ, Gamble M, Schatterny J, Morty RE, Ludwig M, Krause-Kyora B, Stark R, An HJ, Neumann J, Cipollini G, Grimm R, Kilian N, and Zink A
- Subjects
- Humans, Plasmodium falciparum, Microscopy methods, Italy epidemiology, Malaria epidemiology, Malaria, Falciparum epidemiology
- Abstract
Microscopy of mummified visceral tissue from a Medici family member in Italy identified a potential blood vessel containing erythrocytes. Giemsa staining, atomic force microscopy, and immunohistochemistry confirmed Plasmodium falciparum inside those erythrocytes. Our results indicate an ancient Mediterranean presence of P. falciparum, which remains responsible for most malaria deaths in Africa.
- Published
- 2023
- Full Text
- View/download PDF
39. The Lady from Basel's Barfüsserkirche - Molecular confirmation of the Mummy's identity through mitochondrial DNA of living relatives spanning 22 generations.
- Author
-
Wurst C, Maixner F, Castella V, Cipollini G, Hotz G, and Zink A
- Subjects
- DNA, Mitochondrial genetics, Haplotypes, Humans, Sequence Analysis, DNA, Genome, Mitochondrial, Mummies
- Abstract
The identity of the mummified Lady from the Barfüsser Church in Basel, Switzerland has been unsolved for decades, despite the prominent location of the burial place in front of the choir screen. A recent multidisciplinary research approach came up with a possible candidate, Anna Catharina Bischoff who died in Basel in 1787 with an age of 69 years (1719-1787). To verify the identity of the mummy, genealogists of the Citizen Science Basel discovered three living individuals of the maternal lineage of two different family branches, separated from Anna Catharina Bischoff by up to 22 generations. In this study we compare the ancient mitochondrial DNA of the mummy recovered from a premolar to the mitochondrial DNA of these three candidates. Initially the mitochondrial hypervariable regions I and II of the living individuals were screened using the Sanger sequencing method. This was followed by a mitochondrial capture approach and next generation sequencing to enrich for the whole mitochondrial genome of the mummy and one living person. A full mitochondrial genome has been recovered of both individuals sharing an identical haplotype. The sequence was assigned to the mitochondrial haplogroup U5a1+!16192 including two private mutations 10006G and 16293C. Only by using an interdisciplinary approach combining ancient DNA analysis and genealogy a maternal lineage of a non-noble family spanning 22 generations could be confirmed., (Copyright © 2021 Elsevier B.V. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
40. The Iceman's Last Meal Consisted of Fat, Wild Meat, and Cereals.
- Author
-
Maixner F, Turaev D, Cazenave-Gassiot A, Janko M, Krause-Kyora B, Hoopmann MR, Kusebauch U, Sartain M, Guerriero G, O'Sullivan N, Teasdale M, Cipollini G, Paladin A, Mattiangeli V, Samadelli M, Tecchiati U, Putzer A, Palazoglu M, Meissen J, Lösch S, Rausch P, Baines JF, Kim BJ, An HJ, Gostner P, Egarter-Vigl E, Malfertheiner P, Keller A, Stark RW, Wenk M, Bishop D, Bradley DG, Fiehn O, Engstrand L, Moritz RL, Doble P, Franke A, Nebel A, Oeggl K, Rattei T, Grimm R, and Zink A
- Subjects
- Archaeology, Austria, Dietary Fats, Edible Grain, History, Ancient, Humans, Italy, Male, Meat, Diet history, Mummies
- Abstract
The history of humankind is marked by the constant adoption of new dietary habits affecting human physiology, metabolism, and even the development of nutrition-related disorders. Despite clear archaeological evidence for the shift from hunter-gatherer lifestyle to agriculture in Neolithic Europe [1], very little information exists on the daily dietary habits of our ancestors. By undertaking a complementary -omics approach combined with microscopy, we analyzed the stomach content of the Iceman, a 5,300-year-old European glacier mummy [2, 3]. He seems to have had a remarkably high proportion of fat in his diet, supplemented with fresh or dried wild meat, cereals, and traces of toxic bracken. Our multipronged approach provides unprecedented analytical depth, deciphering the nutritional habit, meal composition, and food-processing methods of this Copper Age individual., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2018
- Full Text
- View/download PDF
41. Whole mitochondrial DNA sequencing in Alpine populations and the genetic history of the Neolithic Tyrolean Iceman.
- Author
-
Coia V, Cipollini G, Anagnostou P, Maixner F, Battaggia C, Brisighelli F, Gómez-Carballa A, Destro Bisol G, Salas A, and Zink A
- Subjects
- Austria, Genome, Mitochondrial, Haplotypes, Humans, Mummies, Phylogeny, Phylogeography, DNA, Mitochondrial, Genetics, Population, Sequence Analysis, DNA
- Abstract
The Tyrolean Iceman is an extraordinarily well-preserved natural mummy that lived south of the Alpine ridge ~5,200 years before present (ybp), during the Copper Age. Despite studies that have investigated his genetic profile, the relation of the Iceman´s maternal lineage with present-day mitochondrial variation remains elusive. Studies of the Iceman have shown that his mitochondrial DNA (mtDNA) belongs to a novel lineage of haplogroup K1 (K1f) not found in extant populations. We analyzed the complete mtDNA sequences of 42 haplogroup K bearing individuals from populations of the Eastern Italian Alps - putatively in genetic continuity with the Tyrolean Iceman-and compared his mitogenome with a large dataset of worldwide K1 sequences. Our results allow a re-definition of the K1 phylogeny, and indicate that the K1f haplogroup is absent or rare in present-day populations. We suggest that mtDNA Iceman´s lineage could have disappeared during demographic events starting in Europe from ~5,000 ybp. Based on the comparison of our results with published data, we propose a scenario that could explain the apparent contrast between the phylogeographic features of maternal and paternal lineages of the Tyrolean Iceman within the context of the demographic dynamics happening in Europe from 8,000 ybp.
- Published
- 2016
- Full Text
- View/download PDF
42. The 5300-year-old Helicobacter pylori genome of the Iceman.
- Author
-
Maixner F, Krause-Kyora B, Turaev D, Herbig A, Hoopmann MR, Hallows JL, Kusebauch U, Vigl EE, Malfertheiner P, Megraud F, O'Sullivan N, Cipollini G, Coia V, Samadelli M, Engstrand L, Linz B, Moritz RL, Grimm R, Krause J, Nebel A, Moodley Y, Rattei T, and Zink A
- Subjects
- Asia, Chromosome Mapping, DNA, Bacterial genetics, DNA, Bacterial isolation & purification, Europe, Helicobacter pylori isolation & purification, Human Migration, Humans, Ice Cover microbiology, Mummies microbiology, Phylogeny, Phylogeography, Sequence Analysis, DNA, Genome, Bacterial genetics, Helicobacter Infections microbiology, Helicobacter pylori genetics, Hybridization, Genetic, Stomach microbiology
- Abstract
The stomach bacterium Helicobacter pylori is one of the most prevalent human pathogens. It has dispersed globally with its human host, resulting in a distinct phylogeographic pattern that can be used to reconstruct both recent and ancient human migrations. The extant European population of H. pylori is known to be a hybrid between Asian and African bacteria, but there exist different hypotheses about when and where the hybridization took place, reflecting the complex demographic history of Europeans. Here, we present a 5300-year-old H. pylori genome from a European Copper Age glacier mummy. The "Iceman" H. pylori is a nearly pure representative of the bacterial population of Asian origin that existed in Europe before hybridization, suggesting that the African population arrived in Europe within the past few thousand years., (Copyright © 2016, American Association for the Advancement of Science.)
- Published
- 2016
- Full Text
- View/download PDF
43. Metagenomic analysis reveals presence of Treponema denticola in a tissue biopsy of the Iceman.
- Author
-
Maixner F, Thomma A, Cipollini G, Widder S, Rattei T, and Zink A
- Subjects
- Biopsy, Computational Biology, Humans, Molecular Sequence Data, Nucleotides genetics, Phylogeny, Polymerase Chain Reaction, RNA, Ribosomal genetics, Fossils, Metagenome genetics, Metagenomics methods, Mouth microbiology, Mouth pathology, Treponema denticola genetics
- Abstract
Ancient hominoid genome studies can be regarded by definition as metagenomic analyses since they represent a mixture of both hominoid and microbial sequences in an environment. Here, we report the molecular detection of the oral spirochete Treponema denticola in ancient human tissue biopsies of the Iceman, a 5,300-year-old Copper Age natural ice mummy. Initially, the metagenomic data of the Iceman's genomic survey was screened for bacterial ribosomal RNA (rRNA) specific reads. Through ranking the reads by abundance a relatively high number of rRNA reads most similar to T. denticola was detected. Mapping of the metagenome sequences against the T. denticola genome revealed additional reads most similar to this opportunistic pathogen. The DNA damage pattern of specifically mapped reads suggests an ancient origin of these sequences. The haematogenous spread of bacteria of the oral microbiome often reported in the recent literature could already explain the presence of metagenomic reads specific for T. denticola in the Iceman's bone biopsy. We extended, however, our survey to an Iceman gingival tissue sample and a mouth swab sample and could thereby detect T. denticola and Porphyrimonas gingivalis, another important member of the human commensal oral microflora. Taken together, this study clearly underlines the opportunity to detect disease-associated microorganisms when applying metagenomics-enabled approaches on datasets of ancient human remains.
- Published
- 2014
- Full Text
- View/download PDF
44. Demographic histories, isolation and social factors as determinants of the genetic structure of Alpine linguistic groups.
- Author
-
Coia V, Capocasa M, Anagnostou P, Pascali V, Scarnicci F, Boschi I, Battaggia C, Crivellaro F, Ferri G, Alù M, Brisighelli F, Busby GB, Capelli C, Maixner F, Cipollini G, Viazzo PP, Zink A, and Destro Bisol G
- Subjects
- Ethnicity genetics, Ethnicity history, Evolution, Molecular, Female, History, 15th Century, History, 16th Century, History, 17th Century, History, 18th Century, History, 19th Century, History, 20th Century, History, 21st Century, Humans, Male, Mitochondria genetics, Polymorphism, Single Nucleotide, White People ethnology, Chromosomes, Human, Y genetics, Demography history, Gene Flow, Genetic Variation, Linguistics, White People genetics, White People history
- Abstract
Great European mountain ranges have acted as barriers to gene flow for resident populations since prehistory and have offered a place for the settlement of small, and sometimes culturally diverse, communities. Therefore, the human groups that have settled in these areas are worth exploring as an important potential source of diversity in the genetic structure of European populations. In this study, we present new high resolution data concerning Y chromosomal variation in three distinct Alpine ethno-linguistic groups, Italian, Ladin and German. Combining unpublished and literature data on Y chromosome and mitochondrial variation, we were able to detect different genetic patterns. In fact, within and among population diversity values observed vary across linguistic groups, with German and Italian speakers at the two extremes, and seem to reflect their different demographic histories. Using simulations we inferred that the joint effect of continued genetic isolation and reduced founding group size may explain the apportionment of genetic diversity observed in all groups. Extending the analysis to other continental populations, we observed that the genetic differentiation of Ladins and German speakers from Europeans is comparable or even greater to that observed for well known outliers like Sardinian and Basques. Finally, we found that in south Tyroleans, the social practice of Geschlossener Hof, a hereditary norm which might have favored male dispersal, coincides with a significant intra-group diversity for mtDNA but not for Y chromosome, a genetic pattern which is opposite to those expected among patrilocal populations. Together with previous evidence regarding the possible effects of "local ethnicity" on the genetic structure of German speakers that have settled in the eastern Italian Alps, this finding suggests that taking socio-cultural factors into account together with geographical variables and linguistic diversity may help unveil some yet to be understood aspects of the genetic structure of European populations.
- Published
- 2013
- Full Text
- View/download PDF
45. New insights into the Tyrolean Iceman's origin and phenotype as inferred by whole-genome sequencing.
- Author
-
Keller A, Graefen A, Ball M, Matzas M, Boisguerin V, Maixner F, Leidinger P, Backes C, Khairat R, Forster M, Stade B, Franke A, Mayer J, Spangler J, McLaughlin S, Shah M, Lee C, Harkins TT, Sartori A, Moreno-Estrada A, Henn B, Sikora M, Semino O, Chiaroni J, Rootsi S, Myres NM, Cabrera VM, Underhill PA, Bustamante CD, Vigl EE, Samadelli M, Cipollini G, Haas J, Katus H, O'Connor BD, Carlson MR, Meder B, Blin N, Meese E, Pusch CM, and Zink A
- Subjects
- Base Sequence, Borrelia burgdorferi genetics, Chromosome Mapping, DNA, Mitochondrial genetics, Genetic Predisposition to Disease, History, Ancient, Humans, Lyme Disease history, Mitochondria genetics, Paleontology, Phenotype, Sequence Analysis, DNA, Vascular Calcification, Genome, Human, Genome, Mitochondrial, Mummies microbiology
- Abstract
The Tyrolean Iceman, a 5,300-year-old Copper age individual, was discovered in 1991 on the Tisenjoch Pass in the Italian part of the Ötztal Alps. Here we report the complete genome sequence of the Iceman and show 100% concordance between the previously reported mitochondrial genome sequence and the consensus sequence generated from our genomic data. We present indications for recent common ancestry between the Iceman and present-day inhabitants of the Tyrrhenian Sea, that the Iceman probably had brown eyes, belonged to blood group O and was lactose intolerant. His genetic predisposition shows an increased risk for coronary heart disease and may have contributed to the development of previously reported vascular calcifications. Sequences corresponding to ~60% of the genome of Borrelia burgdorferi are indicative of the earliest human case of infection with the pathogen for Lyme borreliosis.
- Published
- 2012
- Full Text
- View/download PDF
46. Reconstructing the genealogy of a BRCA1 founder mutation by phylogenetic analysis.
- Author
-
Marroni F, Cipollini G, Peissel B, D'Andrea E, Pensabene M, Radice P, Caligo MA, Presciuttini S, and Bevilacqua G
- Subjects
- Haplotypes, Heterozygote, Humans, Models, Genetic, Pedigree, Time Factors, BRCA1 Protein genetics, Founder Effect, Mutation genetics, Phylogeny
- Abstract
Estimating the age of founder mutations may contribute to improve our knowledge of population genetics and evolutionary history of diseases. Previous haplotype analysis suggested that the BRCA1*1499insA mutation was a founder allele, probably originated in Tuscany (Italy). Here, we collected additional pedigrees carrying this mutation, and applied a phylogenetic method for estimating mutation age. A chromosome segment of about 25 cM, including 37 short tandem repeats (STRs) on both sides of the BRCA1 gene (DeCode map), was typed in 50 subjects (28 mutation carriers) from 14 unrelated families. The time to the most recent common ancestor (MRCA) of the mutation carriers was estimated by the length of the shared haplotype between all possible pairs of individuals. A function relating the length of the shared haplotype to the time to the MRCA was obtained by a computer simulation. This approach gives results comparable with those of other existing mutation-dating methods, but does not depend explicitly on population-specific parameters such as allele frequencies, provides narrower confidence intervals (CI), and allows one to build an extended genealogical tree of all mutation carriers. The 1499insA mutation shared by the investigated subjects was estimated to be present in an individual living about 30 generations ago (95% CL 22-56), or 750 years (95% CL 550-1,400).
- Published
- 2008
- Full Text
- View/download PDF
47. RNA-based analysis of BRCA1 and BRCA2 gene alterations.
- Author
-
Bonatti F, Pepe C, Tancredi M, Lombardi G, Aretini P, Sensi E, Falaschi E, Cipollini G, Bevilacqua G, and Caligo MA
- Subjects
- Base Sequence, Breast Neoplasms genetics, DNA Mutational Analysis, Female, Humans, Male, Ovarian Neoplasms genetics, Pedigree, RNA, Messenger metabolism, Sequence Analysis, DNA, Software, Alternative Splicing, Genes, BRCA1, Genes, BRCA2, Germ-Line Mutation, RNA Splice Sites, RNA Splicing
- Abstract
Alterations in BRCA1 and BRCA2 genes account for a large proportion of hereditary breast and ovarian cancers. Mutations and variants of unknown pathological significance have been identified in both genes; however, most of them have been studied only at the genomic level, and their effect on mRNA expression remains unknown. We identified two BRCA1 and six BRCA2 splice site variants, and one BRCA2 alteration at exon 14. Our aim was to ascertain the effect on RNA processing of the variants still unclassified. We found that BRCA1 c.IVS11 + 1G>A, BRCA2 c.7252_7272delinsTG, BRCA2 c.IVS2 + 1G>A, BRCA2 c.IVS13-2A>G, BRCA2 c.IVS21 + 4A>G, and BRCA2 c.9345G>A lead to aberrant transcripts in lymphocytes. Five of these six splice site variants caused a complete inactivation of the mutant allele because they produced frameshift similar to previously described deleterious exonic variants. Therefore, we consider them to be true deleterious mutations, possibly associated with an increased lifetime risk of breast or ovarian cancer. BRCA1 c.IVS17 + 6C>G, BRCA2 c.IVS12-9del4, and BRCA2 IVS1-9del3 represent rare variants, not disrupting normal mRNA processing. The last two BRCA2 genetic variants had not been reported in the Breast Cancer Information Core BIC database.
- Published
- 2006
- Full Text
- View/download PDF
48. [PCR: potential and problems].
- Author
-
Cipollini G and Bevilacqua G
- Subjects
- Polymerase Chain Reaction methods
- Published
- 2005
49. Papillary lesions of the breast: a molecular progression?
- Author
-
Di Cristofano C, Mrad K, Zavaglia K, Bertacca G, Aretini P, Cipollini G, Bevilacqua G, Ben Romdhane K, and Cavazzana A
- Subjects
- Carcinoma, Ductal, Breast genetics, Carcinoma, Intraductal, Noninfiltrating genetics, Female, Gene Deletion, Humans, Loss of Heterozygosity, Statistics, Nonparametric, Biomarkers, Tumor genetics, Breast Neoplasms genetics, Carcinoma, Papillary genetics, Cell Transformation, Neoplastic genetics, Chromosomes, Human, Pair 16 genetics, Genes, p53 genetics, Papilloma, Intraductal genetics
- Abstract
Introduction: Breast papillary lesions represent a heterogeneous group of tumors ranging from benign to malignant, including several intermediate forms. Malignant papillary tumors are rare and their molecular characterization is still limited. A few studies pointed to the presence of specific genetic alterations that could be relevant both for diagnostic purposes and to elucidate tumour development and progression. In order to look into the issue, we compared LOH relative frequencies of four microsatellite markers located on chromosome 16 in a set of morphologically different papillary breast lesions. LOH at TP53 locus was also analyzed throughout lesions., Materials and Methods: Fifteen cases were analyzed. Sections including a malignant papillary lesion, a benign lesion (when available), and normal breast tissue were selected. Fifteen malignant and twelve benign areas were microdissected using the Leica laser microdissection system (AS LMD). After DNA extraction samples were tested for the following markers: TP53, D16S423, D16S310, DS163210 and D16S476, and analyzed on ABI PRISM 3100 (Applied Biosystems, Foster city CA)., Results: Fourteen malignant lesions and twelve paired benign areas appeared to be informative for at least one of the four markers on chromosome 16. In particular, LOH at loci 16p13 and 16q21 was detected in both benign and malignant lesions, whereas LOH at locus 16q23 was limited to malignant lesions. Nine malignant and seven benign lesions were informative for LOH at TP53 locus, that was found to be significantly associated (p=0.01) with the malignant phenotype., Conclusions: Our data suggest an involvement of chromosome 16 mutations in the early steps of breast papillary tumorigenesis. TP53 deletion and possibly LOH at 16q23 appear to play a role as progression factors, being they significantly associated with malignant transformation of breast papilloma.
- Published
- 2005
- Full Text
- View/download PDF
50. Penetrances of breast and ovarian cancer in a large series of families tested for BRCA1/2 mutations.
- Author
-
Marroni F, Aretini P, D'Andrea E, Caligo MA, Cortesi L, Viel A, Ricevuto E, Montagna M, Cipollini G, Federico M, Santarosa M, Marchetti P, Bailey-Wilson JE, Bevilacqua G, Parmigiani G, and Presciuttini S
- Subjects
- Adult, Aged, Breast Neoplasms epidemiology, Chromosome Mapping, Computer Simulation, Female, Humans, Likelihood Functions, Middle Aged, Ovarian Neoplasms epidemiology, Risk, Breast Neoplasms genetics, Genes, BRCA1, Genes, BRCA2, Mutation, Ovarian Neoplasms genetics, Penetrance
- Abstract
Accurate estimates of breast and ovarian cancer penetrance in BRCA1/2 mutation carriers are crucial in genetic counseling. Estimation is difficult because of the low frequency of mutated alleles and the often-uncertain mechanisms of family ascertainment. We estimated the penetrances of breast and ovarian cancers in carriers of BRCA1/2 mutations by maximizing the retrospective likelihood of the genetic model, given the observed test results, in 568 Italian families screened for germline mutations. The software BRCAPRO was used as a probability calculation tool in a Markov Chain Monte Carlo approach. Breast cancer penetrances were 27% (95% CI 20-34%) at age 50 years and 39% (27-52%) at age 70 in BRCA1 carriers, and 26% (0.18-0.34%) at age 50 and 44% (29-58%) at age 70 in BRCA2 carriers, and ovarian cancer penetrances were 14% (7-22%) at age 50 and 43% (21-66%) at age 70 in BRCA1 carriers and 3% (0-7%) at age 50 and 15% (4-26%) at age 70 in BRCA2 carriers. The new model gave a better fit than the current default in BRCAPRO, the likelihood being 70 log units greater; in addition, the observed numbers of mutations in families stratified by gene and by cancer profile were not significantly different from those expected. Our new penetrance functions are appropriate for predicting breast cancer risk, and for determining the probability of carrying BRCA1/2 mutations, in people who are presently referred to genetic counseling in Italy. Our approach could lead to country-customized versions of the BRCAPRO software by providing appropriate population-specific estimates.
- Published
- 2004
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.