A new mutation of BRCA2 gene in an Italian healthy woman with familial breast cancer history.

Heterozygous germ line mutations in the Breast CAncer1 (BRCA1) and BRCA2 genes can lead to a high risk of breast and ovarian cancer, in addition to a significantly increased susceptibility of pancreatic, prostate and male breast cancer. The BRCA2 belongs to the tumor suppressor gene family and the protein encoded by this gene is involved in the repair of chromosomal damage, with an important role in the error-free repair of DNA double strand breaks. After complete sequencing of coding regions and splice junctions of both genes, in a family with breast cancer history, a non previously reported heterozygous mutation in BRCA2 was detected and studied in an Italian healthy female. The direct sequencing disclosed, on exon 15, an insertion (7525_7526insT). The frame shift mutation of BRCA2 causes a disruption of the translational reading frame, resulting in a stop codon 29 amino acids downstream, in the 2538 position of the BRCA2 protein. The mutated allele codifies a truncated protein, lacking the two putative nuclear localization signals (NLSs) that reside within the extreme C-terminal domain of BRCA2. Since this mutant protein not performs a translocation into the nucleus, it is fully non-functional.

Hereditary ovarian cancers: from BRCA mutations to clinical management. A modern appraisal.

In the past few years, ovarian cancer research has focused increasingly on disease prevention; but an increasing number of women refer to gynecology and clinical genetics clinics with a family history of ovarian cancer and inherited familial mutations. The interest on the issue has increased also due to the identification of BReast CAncer1 (BRCA1) and BRCA2 genes mutations. The importance of recognizing the characteristics of hereditary ovarian cancer (HOC) and manage women at risk appropriately will provide more accurate care of the high-risk population. Women at risk can be identified by pedigree analysis and may receive counseling from interdisciplinary cancer genetics clinics, while those at high risk need to receive genetic testing. Risk calculation programs define risks and assist in decision-making in clinical options and genetic testing; they provide information on the risks of the disease, mutation status, and the use of genetic testing in the management of high-risk families. Furthermore, while a large number of surrogate preliminary markers have been identified, there are still limited studies on ovarian cancer genomics. Different options for risk management of HOC are available: surveillance, chemoprevention and prophylactic surgery. Surveillance in HOC high-risk patients is still not accurate. Chemoprevention is currently a controversial topic, because a number of major issues still need to be addressed in developing and testing agents for ovarian cancer chemoprevention. Prophylactic surgery has been shown to effectively decrease cancer risk, and it has the possibility to substantially reduce ovarian cancer mortality.

An outlook on ovarian cancer and borderline ovarian tumors: focus on genomic and proteomic findings.

Among the gynaecological malignancies, ovarian cancer is one of the neoplastic forms with the poorest prognosis and with the bad overall and disease-free survival rates than other gynaecological cancers. Ovarian tumors can be classified on the basis of the cells of origin in epithelial, stromal and germ cell tumors. Epithelial ovarian tumors display great histological heterogeneity and can be further subdivided into benign, intermediate or borderline, and invasive tumors. Several studies on ovarian tumors, have focused on the identification of both diagnostic and prognostic markers for applications in clinical practice. High-throughput technologies have accelerated the process of biomolecular study and genomic discovery; unfortunately, validity of these should be still demonstrated by extensive researches on sensibility and sensitivity of ovarian cancer novel biomarkers, determining whether gene profiling and proteomics could help differentiate between patients with metastatic ovarian cancer and primary ovarian carcinomas, and their potential impact on management. Therefore, considerable interest lies in identifying molecular and protein biomarkers and indicators to guide treatment decisions and clinical follow up. In this review, the current state of knowledge about the genoproteomic and potential clinical value of gene expression profiling in ovarian cancer and ovarian borderline tumors is discussed, focusing on three main areas: distinguishing normal ovarian tissue from ovarian cancers and borderline tumors, identifying different genotypes of ovarian tissue and identifying proteins linked to cancer or tumor development. By these targets, authors focus on the use of novel molecules, developed on the proteomics and genomics researches, as potential protein biomarkers in the management of ovarian cancer or borderline tumor, overlooking on current state of the art and on future perspectives of researches.

HPV viral activity by mRNA-HPV molecular analysis to screen the transforming infections in precancer cervical lesions.

INTRODUCTION: a current problem with the Human papillomavirus (HPV) genital infection is to detect HPV presence and activity in high risk women. MATERIAL AND METHODS: 190 women at risk for HPV-infection underwent a Pap Test as well as a cervico-vaginal mucus sample analysis. The genome amplification of ORF L1 was by REAL-Time PCR by direct sequencing in capillary elettrophoresis of amplified product in Real Time (by ABI PRISM((R)) 310 Genetic Analyzer, Applied Biosystem, USA), followed by HPV genotyping using oligonucleotide probe hybridization. Degenerate primers My09/11, with 450 bp product amplified were utilized in Real Time and in Direct Sequencing. Furthermore, samples were evaluated by mRNA-HPV test to detect the presence of E6 and E7 transcripts. The results were compared with cytology. RESULTS: a total of 62 women were positive for HPV infection (32.6%) and 19 of these had one or more high-risk HPVs (30.6%); the concordance between the two assays was 78.9%, with 21.1% of totally or partially discordant results. Cytological results showed mRNA presence in 4 low grade and 2 high grade squamous intraepithelial lesions. CONCLUSION: the results suggest the potential of E6/E7 detection to target the presence of a transforming HPV infection.