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3. Germline polymorphisms and survival of lung adenocarcinoma patients: A genome-wide study in two European patient series

Author

Galvan, Antonella, Colombo, Francesca, Frullanti, Elisa, Dassano, Alice, Noci, Sara, Wang, Yufei, Eisen, Timothy, Matakidou, Athena, Tomasello, Luisa, Vezzalini, Marzia, Sorio, Claudio, Dugo, Matteo, Ambrogi, Federico, Iacobucci, Ilaria, Martinelli, Giovanni, Incarbone, Matteo, Alloisio, Marco, Nosotti, Mario, Tosi, Davide, Santambrogio, Luigi, Pelosi, Giuseppe, Pastorino, Ugo, Houlston, Richard S., and Dragani, Tommaso A.

Published
2015
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5. Gene expression signature of non-involved lung tissue associated with survival in lung adenocarcinoma patients

Author

Galvan, Antonella, Frullanti, Elisa, Anderlini, Marco, Manenti, Giacomo, Noci, Sara, Dugo, Matteo, Ambrogi, Federico, De Cecco, Loris, Spinelli, Roberta, Piazza, Rocco, Pirola, Alessandra, Gambacorti-Passerini, Carlo, Incarbone, Matteo, Alloisio, Marco, Tosi, Davide, Nosotti, Mario, Santambrogio, Luigi, Pastorino, Ugo, and Dragani, Tommaso A.

Published
2013
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17. Testing of human papillomavirus in lung cancer and non-tumor lung tissue

Author

Galvan Antonella, Noci Sara, Taverna Francesca, Lombardo Claudia, Franceschi Silvia, Pastorino Ugo, and Dragani Tommaso A

Subjects
Biomarker, Cancer, HPV, Lung, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Risk factors for lung cancer, such as cigarette smoking, environmental pollution, asbestos, and genetic determinants, are well-known, whereas involvement of the human papillomavirus (HPV) is still unclear. Methods We examined a series of 100 lung cancer patients from Italy and the UK for the presence of HPV DNA in both lung tumor specimens and adjacent non-tumoral specimens from the same patients. Thirty-five of the most clinically relevant HPV types were assayed using PCR amplification of the highly conserved L1 region of the viral genome followed by hybridization with specific probes. Results No HPV was detected in tumor specimens nor in normal lung tissue of any patient. Conclusions These data indicate that, in this Western series, HPV is not associated with the risk of lung cancer. Our findings will help refine estimates of lung cancer risk in patients affected by a common viral infection involved in other types of human cancer.

Published
2012
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19. A 5'-region polymorphism modulates promoter activity of the tumor suppressor gene MFSD2A

Author

Kunitoh Hideo, Frullanti Elisa, Galvan Antonella, Falvella Felicia S, Colombo Francesca, Ushijima Toshikazu, and Dragani Tommaso A

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background The MFSD2A gene maps within a linkage disequilibrium block containing the MYCL1-EcoRI polymorphism associated with prognosis and survival in lung cancer patients. Survival discrepancies between Asians and Caucasians point to ethnic differences in allelic frequencies of the functional genetic variations. Results Analysis of three single-nucleotide polymorphisms (SNPs) mapping in the MFSD2A 5'-regulatory region using a luciferase reporter system showed that SNP rs12072037, in linkage disequilibrium with the MYCL1-EcoRI polymorphism and polymorphic in Asians but not in Caucasians, modulated transcriptional activity of the MFSD2A promoter in cell lines expressing AHR and ARNT transcription factors, which potentially bind to the SNP site. Conclusion SNP rs12072037 modulates MFSD2A promoter activity and thus might affect MFSD2A levels in normal lung and in lung tumors, representing a candidate ethnically specific genetic factor underlying the association between the MYCL1 locus and lung cancer patients' survival.

Published
2011
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21. Genetic susceptibility variants for lung cancer: replication study and assessment as expression quantitative trait loci

Author

Pintarelli, Giulia, primary, Cotroneo, Chiara Elisabetta, additional, Noci, Sara, additional, Dugo, Matteo, additional, Galvan, Antonella, additional, Delli Carpini, Simona, additional, Citterio, Lorena, additional, Manunta, Paolo, additional, Incarbone, Matteo, additional, Tosi, Davide, additional, Santambrogio, Luigi, additional, Dragani, Tommaso A., additional, and Colombo, Francesca, additional

Published
2017
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22. Read-through transcripts in normal human lung parenchyma are down-regulated in lung adenocarcinoma

Author

Pintarelli, Giulia, primary, Dassano, Alice, additional, Cotroneo, Chiara E., additional, Galvan, Antonella, additional, Noci, Sara, additional, Piazza, Rocco, additional, Pirola, Alessandra, additional, Spinelli, Roberta, additional, Incarbone, Matteo, additional, Palleschi, Alessandro, additional, Rosso, Lorenzo, additional, Santambrogio, Luigi, additional, Dragani, Tommaso A., additional, and Colombo, Francesca, additional

Published
2016
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25. Cis-acting genetic elements at or near the Pas1 locus control Kras2 mutations and gene expression in lung tumors from mice selected for acute inflammatory response

Author

Ribeiro Orlando, Dragani Tommaso, De Franco Marcelo, Ibaez Olga, Galvan Antonella, Cabrera Wafa, Jensen Jos, Starobinas Nancy, Manenti Giacomo, and Borrego Andrea

Subjects
Lung, medicine.anatomical_structure, Inflammatory response, Gene expression, Immunology, Cancer research, medicine, Immunology and Allergy, Biology, Cis acting
Published
2013
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27. Germline polymorphisms and survival of lung adenocarcinoma patients: A genome‐wide study in two European patient series

Author

Galvan, Antonella, primary, Colombo, Francesca, additional, Frullanti, Elisa, additional, Dassano, Alice, additional, Noci, Sara, additional, Wang, Yufei, additional, Eisen, Timothy, additional, Matakidou, Athena, additional, Tomasello, Luisa, additional, Vezzalini, Marzia, additional, Sorio, Claudio, additional, Dugo, Matteo, additional, Ambrogi, Federico, additional, Iacobucci, Ilaria, additional, Martinelli, Giovanni, additional, Incarbone, Matteo, additional, Alloisio, Marco, additional, Nosotti, Mario, additional, Tosi, Davide, additional, Santambrogio, Luigi, additional, Pelosi, Giuseppe, additional, Pastorino, Ugo, additional, Houlston, Richard S., additional, and Dragani, Tommaso A., additional

Published
2014
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30. Pristane-Induced Arthritis Loci Interact with the Slc11a1 Gene to Determine Susceptibility in Mice Selected for High Inflammation

Author

De Franco, Marcelo, primary, Peters, Luciana C., additional, Correa, Mara A., additional, Galvan, Antonella, additional, Canhamero, Tatiane, additional, Borrego, Andrea, additional, Jensen, José R., additional, Gonçalves, Jussara, additional, Cabrera, Wafa H. K., additional, Starobinas, Nancy, additional, Ribeiro, Orlando G., additional, Dragani, Tommaso, additional, and Ibañez, Olga M., additional

Published
2014
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31. Genetic control of renal tumorigenesis by the mouse Rtm1 locus

Author

Jensen, José Ricardo, primary, Galvan, Antonella, additional, Borrego, Andrea, additional, Hanna Koury Cabrera, Wafa, additional, Ribeiro, Orlando Garcia, additional, Starobinas, Nancy, additional, De Franco, Marcelo, additional, Colecchia, Maurizio, additional, Bertolotti, Alessia, additional, Dragani, Tommaso Antonio, additional, and Martinez Ibañez, Olga Célia, additional

Published
2013
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34. Multiple Loci Modulate Opioid Therapy Response for Cancer Pain

Author

Galvan, Antonella, primary, Skorpen, Frank, additional, Klepstad, Pål, additional, Knudsen, Anne Kari, additional, Fladvad, Torill, additional, Falvella, Felicia S., additional, Pigni, Alessandra, additional, Brunelli, Cinzia, additional, Caraceni, Augusto, additional, Kaasa, Stein, additional, and Dragani, Tommaso A., additional

Published
2011
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35. Multiple Genetic Loci Modulate Lung Adenocarcinoma Clinical Staging

Author

Frullanti, Elisa, primary, Galvan, Antonella, additional, Falvella, Felicia S., additional, Manenti, Giacomo, additional, Colombo, Francesca, additional, Vannelli, Alberto, additional, Incarbone, Matteo, additional, Alloisio, Marco, additional, Nosotti, Mario, additional, Santambrogio, Luigi, additional, Gonzalez-Neira, Anna, additional, Pastorino, Ugo, additional, and Dragani, Tommaso A., additional

Published
2011
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36. Genetic heterogeneity of inflammatory response and skin tumorigenesis in phenotypically selected mouse lines

Author

Galvan, Antonella, primary, Vorraro, Francisca, additional, Cabrera, Wafa Hanna Koury, additional, Ribeiro, Orlando Garcia, additional, Pazzaglia, Simonetta, additional, Mancuso, Mariateresa, additional, Zolin, Anna, additional, Milani, Silvano, additional, Saran, Anna, additional, Ibañez, Olga M., additional, and Dragani, Tommaso A., additional

Published
2010
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38. Genetic Control of IL-1β Production and Inflammatory Response by the Mouse Irm1 Locus

Author

Vorraro, Francisca, primary, Galvan, Antonella, additional, Cabrera, Wafa Hanna Koury, additional, Carneiro, Patricia Santos, additional, Ribeiro, Orlando Garcia, additional, De Franco, Marcelo, additional, Starobinas, Nancy, additional, Jensen, José Ricardo, additional, Seman, Michel, additional, Dragani, Tommaso A., additional, and Ibañez, Olga Célia Martinez, additional

Published
2010
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44. A polygenic model with common variants may predict lung adenocarcinoma risk in humans

Author

Galvan, Antonella, primary, Falvella, Felicia S., additional, Spinola, Monica, additional, Frullanti, Elisa, additional, Leoni, Vera P., additional, Noci, Sara, additional, Alonso, Maria R., additional, Zolin, Anna, additional, Spada, Elena, additional, Milani, Silvano, additional, Pastorino, Ugo, additional, Incarbone, Matteo, additional, Santambrogio, Luigi, additional, Neira, Anna Gonzalez, additional, and Dragani, Tommaso A., additional

Published
2008
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46. Met proto-oncogene juxtamembrane rare variations in mouse and humans: differential effects of Arg and Cys alleles on mouse lung tumorigenesis

Author

Zaffaroni, Daniela, primary, Spinola, Monica, additional, Galvan, Antonella, additional, Falvella, F Stefania, additional, Pazzaglia, Simonetta, additional, Saran, Anna, additional, Mancuso, Maria Teresa, additional, Galbiati, Federica, additional, Pignatiello, Carmen, additional, Cabrera, Wafa, additional, Ibanez, Olga, additional, Manenti, Giacomo, additional, and Dragani, Tommaso A, additional

Published
2004
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47. Mouse Pulmonary Adenoma Susceptibility 1 Locus Is an Expression QTL Modulating Kras-4A.

Author

Dassano, Alice, Colombo, Francesca, Trincucci, Gaia, Frullanti, Elisa, Galvan, Antonella, Pettinicchio, Angela, De Cecco, Loris, Borrego, Andrea, Martinez Ibañez, Olga Célia, Dragani, Tommaso A., and Manenti, Giacomo

Subjects
LUNG diseases, ANIMAL models in research, GENETICS of disease susceptibility, GENE mapping research, LOCUS (Genetics), GENETICS
Abstract

Pulmonary adenoma susceptibility 1 (Pas1) is the major locus responsible for lung tumor susceptibility in mice; among the six genes mapping in this locus, Kras is considered the best candidate for Pas1 function although how it determines tumor susceptibility remains unknown. In an (A/J×C57BL/6)F4 intercross population treated with urethane to induce lung tumors, Pas1 not only modulated tumor susceptibility (LOD score = 48, 69% of phenotypic variance explained) but also acted, in lung tumor tissue, as an expression quantitative trait locus (QTL) for Kras-4A, one of two alternatively spliced Kras transcripts, but not Kras-4B. Additionally, Kras-4A showed differential allelic expression in lung tumor tissue of (A/J×C57BL/6)F4 heterozygous mice, with significantly higher expression from the A/J-derived allele; these results suggest that cis-acting elements control Kras-4A expression. In normal lung tissue from untreated mice of the same cross, Kras-4A levels were also highly linked to the Pas1 locus (LOD score = 23.2, 62% of phenotypic variance explained) and preferentially generated from the A/J-derived allele, indicating that Pas1 is an expression QTL in normal lung tissue as well. Overall, the present findings shed new light on the genetic mechanism by which Pas1 modulates the susceptibility to lung tumorigenesis, through the fine control of Kras isoform levels. [ABSTRACT FROM AUTHOR]

Published
2014
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48. Pristane-Induced Arthritis Loci Interact with the Slc11a1 Gene to Determine Susceptibility in Mice Selected for High Inflammation.

Author

De Franco, Marcelo, Peters, Luciana C., Correa, Mara A., Galvan, Antonella, Canhamero, Tatiane, Borrego, Andrea, Jensen, José R., Gonçalves, Jussara, Cabrera, Wafa H. K., Starobinas, Nancy, Ribeiro, Orlando G., Dragani, Tommaso, and Ibañez, Olga M.

Subjects
ARTHRITIS, LOCUS (Genetics), LABORATORY mice, GENE expression, NEUTROPHILS, INFLAMMATION, DISEASE susceptibility
Abstract

AIRmax (maximal inflammation) and AIRmin (minimal inflammation) mice show distinct susceptibilities to pristane-induced arthritis (PIA). The Slc11a1 gene, which regulates macrophage and neutrophil activity, is involved in this infirmity. AIRmaxSS mice homozygous for the non-functional Slc11a1 S (gly169asp) allele obtained by genotype-assisted crosses from AIRmax and AIRmin mice are more susceptible than mice homozygous for the Slc11a1 resistant (R) allele. The present work sought to identify the quantitative trait loci (QTL) regulating PIA and to examine the interactions of these QTL with Slc11a1 alleles in modulating PIA. Mice were given two ip injections of 0.5 mL pristane at 60 day intervals, and the incidence and severity of PIA was scored up to 160 days. Genome-wide linkage studies were performed to search for arthritis QTL in an F2 (AIRmax × AIRmin, n = 290) population. Significant arthritis QTL (LODscore>4) were detected on chromosomes 5 and 8, and suggestive QTL on chromosomes 7, 17 and 19. Global gene expression analyses performed on Affymetrix mouse 1.0 ST bioarrays (27k genes) using RNA from arthritic or control mice paws showed 419 differentially expressed genes between AIRmax and AIRmin mice and demonstrated significantly (P<0.001) over-represented genes related to inflammatory responses and chemotaxis. Up-regulation of the chemokine genes Cxcl1, Cxcl9, Cxcl5, Cxcl13 on chromosome 5 was higher in AIRmaxSS than in the other lines. Macrophage scavenger receptor 1 and hemeoxigenase (decycling) 1 genes on chromosome 8 were also expressed at higher levels in AIRmaxSS mice. Our results show that the gene expression profiles of the two arthritis QTL (on chromosomes 5 and 8) correlate with Slc11a1 alleles, resulting in enhanced AIRmaxSS mice susceptibility to PIA. [ABSTRACT FROM AUTHOR]

Published
2014
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49. Genetic susceptibility variants for lung cancer: replication study and assessment as expression quantitative trait loci

Author

Lorena Citterio, Matteo Dugo, Chiara E. Cotroneo, Tommaso A. Dragani, Paolo Manunta, Matteo Incarbone, Francesca Colombo, Luigi Santambrogio, Simona Delli Carpini, Giulia Pintarelli, Antonella Galvan, Davide Tosi, Sara Noci, Pintarelli, Giulia, Cotroneo, Chiara Elisabetta, Noci, Sara, Dugo, Matteo, Galvan, Antonella, Delli Carpini, Simona, Citterio, Lorena, Manunta, Paolo, Incarbone, Matteo, Tosi, Davide, Santambrogio, Luigi, Dragani, Tommaso A, and Colombo, Francesca

Subjects
Adult, Male, 0301 basic medicine, Proteasome Endopeptidase Complex, Lung Neoplasms, Quantitative Trait Loci, SNP, Adenocarcinoma of Lung, Single-nucleotide polymorphism, Adenocarcinoma, Biology, Polymorphism, Single Nucleotide, survival, Article, 03 medical and health sciences, 0302 clinical medicine, lung adenocarcinoma risk, medicine, Genetic predisposition, Humans, Genetic Predisposition to Disease, Allele, Lung cancer, Iron Regulatory Protein 2, Gene, Aged, Aged, 80 and over, Genetics, Multidisciplinary, Middle Aged, Endonucleases, medicine.disease, DNA-Binding Proteins, Gene Expression Regulation, Neoplastic, 030104 developmental biology, 030220 oncology & carcinogenesis, Expression quantitative trait loci, differential allelic expression, Female, ERCC1, Genome-Wide Association Study
Abstract

Many single nucleotide polymorphisms (SNPs) have been associated with lung cancer but lack confirmation and functional characterization. We retested the association of 56 candidate SNPs with lung adenocarcinoma risk and overall survival in a cohort of 823 Italian patients and 779 healthy controls, and assessed their function as expression quantitative trait loci (eQTLs). In the replication study, eight SNPs (rs401681, rs3019885, rs732765, rs2568494, rs16969968, rs6495309, rs11634351, and rs4105144) associated with lung adenocarcinoma risk and three (rs9557635, rs4105144, and rs735482) associated with survival. Five of these SNPs acted as cis-eQTLs, being associated with the transcription of IREB2 (rs2568494, rs16969968, rs11634351, rs6495309), PSMA4 (rs6495309) and ERCC1 (rs735482), out of 10,821 genes analyzed in lung. For these three genes, we obtained experimental evidence of differential allelic expression in lung tissue, pointing to the existence of in-cis genomic variants that regulate their transcription. These results suggest that these SNPs exert their effects on cancer risk/outcome through the modulation of mRNA levels of their target genes.

Published
2017

50. Unique microRNA-profiles in EGFR-mutated lung adenocarcinomas.

Author

Bjaanaes MM, Halvorsen AR, Solberg S, Jørgensen L, Dragani TA, Galvan A, Colombo F, Anderlini M, Pastorino U, Kure E, Børresen-Dale AL, Brustugun OT, and Helland A

Subjects
Adenocarcinoma genetics, Adenocarcinoma mortality, Adenocarcinoma of Lung, Aged, Cohort Studies, DNA Mutational Analysis, Female, Humans, Kaplan-Meier Estimate, Lung Neoplasms genetics, Lung Neoplasms mortality, Male, MicroRNAs metabolism, Middle Aged, Mutation, Oligonucleotide Array Sequence Analysis, Proportional Hazards Models, Proto-Oncogene Proteins genetics, Proto-Oncogene Proteins p21(ras), ras Proteins genetics, Adenocarcinoma metabolism, ErbB Receptors genetics, Lung Neoplasms metabolism, MicroRNAs genetics, Transcriptome
Abstract

The findings of mutations and the development of targeted therapies have improved lung cancer management. Still, the prognosis remains poor, and we need to know more about the genetic and epigenetic alterations in lung cancer. MicroRNAs are involved in crucial biological processes like carcinogenesis by regulating gene expression at the post-transcriptional level. In this project, we have studied the microRNA expression of lung adenocarcinomas and corresponding normal lung tissue and correlated the expression with clinical data and EGFR- and KRAS-mutational status. Agilent microarrays have been used, examining microRNA expression in 154 surgically resected lung adenocarcinomas and 20 corresponding normal lung tissue samples. Findings were confirmed by RT-qPCR in the same cohort and in an independent cohort of 103 lung cancer patients. EGFR and KRAS mutation analyses were also performed. 129 microRNAs were significantly differentially expressed in lung adenocarcinomas compared with normal lung tissue, and 17 microRNAs were differentially expressed between EGFR-mutated and EGFR wildtype tumors. We identified microRNAs associated with time to progression. We have identified several aberrantly expressed microRNAs that discriminate lung adenocarcinomas from normal lung tissue, and hence may be potential biomarkers for early detection. We have found microRNAs that are differentially expressed between EGFR-mutated and EGFR wildtype lung adenocarcinomas, suggesting that microRNAs can be used as molecular biomarkers in classification. We hypothesize that microRNA expression can be used as biomarkers for clinical course., (© 2014 The Authors. Published by Wiley Periodicals, Inc. on behalf of UICC.)

Published
2014
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