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Copyright of Canadian Bulletin of Medical History is the property of University of Toronto Press and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Hereditary ovarian carcinomas represent 10% of cases of the around 4,500 yearly ovarian cancers in France. They principally consist of high-grade serous carcinomas. They are especially observed in mutation carriers on genes BRCA1 or 2 and, at a lesser degree, on genes of the hereditary non-polyposis colorectal cancer (HNPCC) syndrome. Due to the absence of an effective screening method for this highly lethal disease, laparoscopic prophylactic adnexectomy is strongly recommended as soon as possible, after a genetic counselling session. However, not all women accept the outcomes of an early menopause, especially if a substitutive treatment is contra-indicated. Recent data obtained from the thorough examination of risk-reducing salpingo-oophorectomy (RRSO) specimens highlight the pivotal role of the Fallopian tube in the pathogenesis of most ovarian carcinomas, especially its fimbrial end for the high-grade serous subtype, so frequent with mutation carriers. Thus, for these at-risk women, reluctant to RRSO, the idea of a temporary prophylactic surgery, limited to a bilateral radical fimbriectomy until oophorectomy at menopause, is being assessed in a prospective study. Meanwhile, due to these informations, it is advocated as well to perform salpingectomies in non-at-risk patients, candidates for a conservative hysterectomy or a surgical tubal ligation, as a primary prophylaxis of this dreadful disease. [ABSTRACT FROM AUTHOR]

Summary: Tumor predisposition in children is rare, accounting for approximately 10% of all cancers in childhood. Tumor predisposition involves very rare tumors such as pleuropulmonary blastoma, adrenocortical carcinoma, hepatoblastoma, rhabdoid tumors, optic pathway glioma, as well as rare tumors such as retinoblastoma, medulloblastoma, nephroblastoma, or more frequent tumors such as sarcomas, neuroblastoma, and leukemias. The identification of these predispositions is important for improved management for both the child and relatives. Prenatal and preimplantation genetic diagnosis are options that could be considered for young parents in a perspective of future pregnancies. This manuscript describes the main tumor predispositions in childhood. From each histological subtype, the different diagnosis directions are discussed in view of these main tumor predispositions. [ABSTRACT FROM AUTHOR]

Concomitant chemoradiotherapy can constitute an alternative to surgical approach in selected patients with bladder carcinoma. TNM staging, histological grading, renal and performance status represent the main prognostic factors useful to define the therapeutic strategy. Biological and genetic factors are still controversial in medical practice. The activation of oncogenes seems to characterize the initiation of superficial low-grade tumors and the mutations in the tumor suppressor genes (PTEN, TP53 and RB) appear as the most important biological features in the in situ and invasive tumors. The expression of p53, Rb, Bcl-2 has an obvious prognostic role but the published studies onmolecular factors predictive of radiosensibility are heterogeneous. [ABSTRACT FROM AUTHOR]

Abstract: The impact of curative radiotherapy depends mainly on the total dose delivered homogenously in the targeted volume. Nevertheless, the dose delivered to the surrounding healthy tissues may reduce the therapeutic ratio of many radiation treatments. Two different side effects (acute and late) can occur during and after radiotherapy. Of particular interest are the radiation-induced sequelae due to their irreversibility and the potential impact on daily quality of life. In a same population treated in one centre with the same technique, it appears that individual radiosensitivity clearly exists. In the hypothesis that genetic is involved in this area of research, lymphocytes seem to be the tissue of choice due to easy accessibility. Recently, low percentage of CD4 and CD8 lymphocyte apoptosis were shown to be correlated with high grade of sequelae. In addition, recent data suggest that patients with severe radiation-induced late side effects possess four or more single nucleotide polymorphisms (SNP) in candidate genes (ATM, SOD2, TGFB1, XRCC1, and XRCC3) and low radiation-induced CD8 lymphocyte apoptosis in vitro. On-going studies are being analyzing the entire genome using a Genome-wide association study (GWAS) analysis. [ABSTRACT FROM AUTHOR]

Abstract: High risk may be defined as either an absolute risk greater than 20 % or a relative risk greater than 4. Concerning breast and ovarian cancer, high risk patients include carriers of a constitutive deleterious mutation of BRCA1 or BRCA2 genes, patients with a significant family history of breast or ovarian cancer, and patients who have been diagnosed a benign breast lesion with a high risk of degeneration, i.e. atypical hyperplasia. Following up such patients relies on specific strategies. A center including a large panel of physicians involved in the various modalities for patients’ management (geneticians, radiologists, gynecologists, plastic surgeons, pathologists, endocrinologists, psychologists, medical oncologists) has been created at Tenon Hospital with this purpose. The collaboration of these different specialists with the referent physician of the patient allows for the definition and the implementation of a patient-centered follow-up continuously updated to take into account the different periods of a woman''s life, according to best practices recommendations and the evolving state-of-the art. [Copyright &y& Elsevier]

Ovarian sex cord-stromal tumors are rare tumors that originate from the nongerminal cells of ovary. Two decades ago, the identification of juvenile granulosa-cell tumors (GCT), as a specific entity inside this group, allowed a better treatment of these tumors in children. However, little data have been reported on the natural course of the disease and reliable prognostic factors have not been yet defined. We here review the clinical and genetics aspects of granulosa tumors, based on a series of 40 children. This national collaborative study involved the French Society of Children Cancer and eight clinical departments of pediatric endocrinology. We found that early diagnosis of a tumor, revealed by clinical signs of hyperoestrogeny, is an important prognostic factor. The pathophysiology of these tumors is still debatable and several cellular- and molecular-abnormal signals could be implicated in their development. The role of growth factors and oncogenes through the signaling pathway of MAP kinase is still discussed. According to our data, FSH signaling-transduction pathway, such as a constitutionally activated Gαs, could also be implicated in the induction of granulosa cell proliferation and seems to modulate the invasiveness of the tumor. Last, we have described a low-expression pattern or an extinction of an ovarian-determination gene, FOXL2, which is related to a worse prognosis of this tumor. [Copyright &y& Elsevier]

From the biologist’s viewpoint, the main characteristic of CUP tumours is the imbalance between the growth of metastases and the relative or absolute growth inhibition of the primary tumour. Recent studies have highlighted a limited clonal divergence between the various CUP tumour sites. This suggests that the cellular metastatic functions — such asmotility, isolated cell survival and invasiveness — are acquired before the tumour spread, either in a cryptic primary site or in a metastatic initial take-over site. Data from our working group suggest that some types of TP53 gene mutations are preferentially observed in CUP tumours. In addition, our studies of functional genomics show that some genes that control metastatic functions have distinct expression patterns in CUP and secondary metastases. [ABSTRACT FROM AUTHOR]

Summary: Colorectal cancer is rare in children and adolescents. It is usually associated with predisposing genetic factors, aggressive histology, and poor prognosis. Two familial syndromes are best characterized, hereditary nonpolyposis colorectal cancer and familial adenomatous polyposis. They are autosomal dominant inherited disorders. We report the case of a 14-year-old girl having a Dukes D adenocarcinoma of the rectum with peritoneal extension and bone metastases. [Copyright &y& Elsevier]

Abstract: The goal of this review is to briefly present the main recent advances of research in malignant gliomas and to consider future developments, in a clinical perspective. The main challenges appear to be the following: (1) To better understand the etiology of gliomas and to differentiate the respective roles of environmental and genetic factors. (2) To improve the diagnostic and follow up tools, not only through refined neuroimaging techniques but also by discovering serum biomarkers. (3) To build a reliable molecular classification of gliomas that may be used for diagnostic and therapeutic purposes. (4) To develop a “molecular-based” clinical research. Neuro-Oncology has now reached a new therapeutic era and many methodological and medico-economic questions need to be solved. [Copyright &y& Elsevier]

Copyright of Sciences Sociales et Santé is the property of John Libbey Eurotext Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The molecular diagnosis of a genetic predisposition to breast cancer is now routinely available. BRCA1 and BRCA2 deleterious germline mutations confer very high risks of breast (80% by age 70 years) and ovarian cancer (15–40%). This justifies specific measures of screening, prevention and specific specialized care. The indications, methods and practical consequences of the diagnosis of a genetic predisposition are summarized, and specific care measures presented. [ABSTRACT FROM AUTHOR]

Copyright of EMC-Pneumologie is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Establishment and maintenance of epithelial cell polarity rely on finely tuned protein networks comprising cell surface molecules, cytoplasmic adaptors, and enzymes connected to the actin cytoskeleton. Oncogenes and tumor suppressors promote cell proliferation and resistance to apoptosis and, in many cases, alter some of these molecular scaffolds, and profoundly affect the epithelial cytoarchitecture. Reciprocally, loss of central actors of epithelial polarity unleashes normally repressed signaling pathways and perturb the shape and functions of epithelial tissues. Among the newcomers impacting on epithelial integrity, Scribble is a scaffold protein of a remarkable importance that furthermore displays a tumor suppressing activity in Drosophila melanogaster. Together with Discs Large (Dlg) and Lethal Giant Larvae (Lgl), two known tumor suppressors, Scribble acts on the correct positioning of epithelial junctions required to organize functional epithelial sheets. Scribble, Dlg and Lgl proteins are well conserved during evolution at the molecular and subcellular level implying their potential role in cell polarity and tumorigenesis in humans. Recent findings on hScrib, the human orthologue of Scribble, are discussed here. [Copyright &y& Elsevier]

Algorithm decision in adjuvant (hormonal and/or chemotherapy) breast cancer therapy was the purpose of San Gallen and Washington conferences. The selection of systematic adjuvant therapy is based on clinical and pathological prognosis and predictive factors: age, tumour size, node involment, histologic grade and expression of hormonal receptor. Over the last few years significant progress in fundamental science has been made. The development of new molecular tools (microarray, proteomic) has enabled the identification of therapeutic targets and molecular prognostic and predictive factors. In this review, we focus on the retrospective and prospective prognoses as well as predictive factors in adjuvant breast cancer. [ABSTRACT FROM AUTHOR]

Predicting the future, so as to direct it towards the most favourable position, is the aim of all medical activity. Technological advances are providing new tools, with the aim of identifying subgroups of people that are at higher risk and for whom the more aggressive procedures are, undoubtedly, desirable. The current challenges are to better define the sub-groups, to propose procedures proportionate to the risks and to move on, as quickly as possible, from assumptions to structured programmes of care. [ABSTRACT FROM AUTHOR]

Abstract This article examines how cancer genetics has emerged as a focus for research and healthcare in Cuba and Brazil. Drawing on ethnographic research undertaken in community genetics clinics and cancer genetics services, the article examines how the knowledge and technologies associated with this novel area of healthcare are translated and put to work by researchers, health professionals, patients and their families in these two contexts. It illuminates the comparative similarities and differences in how cancer genetics is emerging in relation to transnational research priorities, the history and contemporary politics of public health and embodied vulnerability to cancer that reconfigures the scope and meaning of genomics as “personalised” medicine.

Introduction: Next generation sequencing allows the simultaneous analysis of large panel of genes for families or individuals with a strong suspicion of hereditary breast and/or ovarian cancer (HBOC). Because of lack of guidelines, several panels of genes potentially involved in HBOC were designed, with large disparities not only in their composition but also in medical care offered to mutation carriers. Then, homogenization in practices is needed., Methods: The French Genetic and Cancer Group (GGC) - Unicancer conducted an exhaustive bibliographic work on 18 genes of interest. Only publications with unbiased risk estimates were retained., Results: The expertise of each 18 genes was based on clinical utility criteria, i.e. a relative risk of cancer of 4 and more, available medical tools for screening and prevention of mutation carriers, and pre-symptomatic genetic tests for relatives. Finally, 13 genes were selected to be included in a HBOC diagnosis gene panel: BRCA1, BRCA2, PALB2, TP53, CDH1, PTEN, RAD51C, RAD51D, MLH1, MSH2, MSH6, PMS2, EPCAM. The reasons for excluding NBN, RAD51B, CHEK2, STK11, ATM, BARD1, BRIP1 from the HBOC diagnosis panel are presented. Screening, prevention and genetic counselling guidelines were detailed for each of the 18 genes., Discussion: Due to the rapid increase in knowledge, the GGC has planned a yearly update of the bibliography to take into account new findings. Furthermore, genetic-epidemiological studies are being initiated to better estimate the cancer risk associated with genes which are not yet included in the HBOC diagnosis panel., (Copyright © 2018 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)