1,721,001 research outputs found
Retesting BRCA1/BRCA2 mutation negative male breast cancer patients using next generation sequencing technologies
No full textWe read with great interest the study by Moran and colleagues, entitled ‘‘Revisiting breast cancer patients who previously tested negative for BRCA mutations using a 12- gene panel’’ recently published in this journal [1]. Using next generation sequencing (NGS) technologies, the authors re-assessed women affected by breast cancer who had previously tested negative for mutations in the large BRCA1 exon 11 and BRCA2 exons 10–11 by the protein truncation test (PTT). Specifically, they evaluated the prevalence of mutations in 12 breast cancer susceptibility genes, including BRCA1 and BRCA2, in 190 female breast
cancer cases with a strong family history of breast cancer. Six mutations were detected in BRCA1 and BRCA2; in particular, one of these mutations (c.893_899delCAGTTGTinsTACTTCAG, p.Thr298fs) was detected in BRCA2 exon 10, previously screened by PTT. Overall, six women who had previously received a negative test result for BRCA1 and BRCA2 mutations using the PTT were found to carry pathogenic mutations in these two highpenetrance
genes
Breast cancer: not only a "woman's" diseases
No full textMale breast cancer (MBC) is a rare disease compared with female breast cancer (FBC), but its incidence is increasing. Because of its rarity, MBC is often compared with FBC and our current understanding regarding MBC biology, natural history and treatment strategies has been largely extrapolated from the female counterpart.
Based on age-frequency distribution, age-specific incidence rate patterns and prognostic factors profiles, MBC is considered similar to late-onset post-menopausal estrogen/progesterone receptors (ER/PR)-positive FBC. This suggests that common BC risk factors may affect both genders. Indeed, similar to BC in women, MBC is likely to be caused by the concurrent effects of different risk factors, including hormonal, environmental and genetic risk factors. However, clinical and pathological characteristics of MBC do not exactly overlap FBC. Compared with women, BC occurs in men later in life, is mostly represented by invasive ductal carcinoma with higher stage, lower grade and ER/PR expression.
Although rare, MBC remains a substantial cause for morbidity and mortality in men, probably because of its occurrence in advanced age and delayed diagnosis. MBC treatment generally follows the same indications as post-menopausal FBC. BC mortality and survival rates have improved significantly over time for both male and female BC, but the improvement for male is smaller if compared to female patients, thus suggesting a delay or non-appropriate utilization of adjuvant therapy.
Overall, much still needs to be learned about MBC and, because of its rarity, the main effort is to develop national and international consortia for moving forward in our understanding of MBC
Gene promoter methylation and DNA repair capacity in monozygotic twins with discordant smoking habits.
No full textThe influence of DNA repair capacity, plasma nutrients and tobacco smoke exposure on DNA methylation was investigated in blood cells of twenty-one couples of monozygotic twins with discordant smoking habits. All study subjects had previously been characterized for mutagen sensitivity with challenge assays with ionizing radiation in peripheral blood lymphocytes. Plasma levels of folic acid, vitamin B12 and homocysteine were also available from a previous investigation. In this work DNA methylation in the promoter region of a panel of ten genes involved in cell cycle control, differentiation, apoptosis and DNA repair (p16, FHIT, RAR, CDH1, DAPK1, hTERT, RASSF1A, MGMT, BRCA1 and PALB2) was assessed in the same batches of cells isolated for previous studies, using the methylation-sensitive high-resolution melting technique. Fairly similar profiles of gene promoter methylation were observed within co-twins compared to unrelated subjects (p= 1.23 × 10(-7)), with no significant difference related to smoking habits (p = 0.23). In a regression analysis the methylation index of study subjects, used as synthetic descriptor of overall promoter methylation, displayed a significant inverse correlation with radiation-induced micronuclei (p = 0.021) and plasma folic acid level (p = 0.007) both in smokers and in non-smokers. The observed association between repair of radiation-induced DNA damage and promoter methylation suggests the involvement of the DNA repair machinery in DNA modification. Data also highlight the possible modulating effect of folate deficiency on DNA methylation and the strong influence of familiarity on the individual epigenetic profile
Proffered papers and posters presented at the Sixth International Symposium on Hereditary Breast and Ovarian Cancer— BRCA: Challenges and Opportunities
No full textPoster P100
Whole-Exome Sequencing Revealed a Novel PALB2 Mutation in a Male Breast Cancer Family
Objectives Male breast cancer (mbc) is a rare disease, whose causation appears to be largely associated with genetic factors. Whole-exome sequencing (wes) is a powerful tool to explore the heritability of complex diseases, including breast cancer (bca). Our aim was to evaluate whether rare mutations may explain a fraction of mbc not accounted for by BRCA1/2 genes. Here, we applied wes analysis to a high-risk mbc family.
Methods A BRCA1/2–negative family with 2 first-degree male and 4 female bca cases was selected for the study. Peripheral-blood dna samples from 1 male and 2 female bca cases were examined. Libraries were prepared and sequenced on the Illumina HiSeq instrument. A bioinformatic pipeline available at https://bioinformatics.cineca.it/wep/ was used. A validation series of 48 high-risk BRCA1/2–negative mbc patients from the Italian
Multicenter Study on mbc was analyzed by Sanger sequencing.
Results A novel PALB2 truncating mutation, c.419delA (p.K140fsX35), was identified by wes in a female bca case and her paternal uncle, diagnosed with melanoma and bca, but not in her maternal aunt, affected with bca;
her father, diagnosed with bca, was an obligate mutation carrier. PALB2 mutational analysis of 48 high-risk mbcs identified another truncating mutation, c.1984A>T (p.K662X), in a man diagnosed with breast, lung, and
prostate cancer, and with family history of bca. Overall, 3/50 high-risk mbcs (6%) were carriers of PALB2 pathogenic mutations.
Conclusions This study highlights the importance of a particular selection of pedigrees including mbc to better define the fraction of bca attributable to genetic predisposition. Our results add to the accumulating evidence that PALB2 is strongly involved in bca risk in both sexes. Consideration should be given to clinical testing for PALB2 in BRCA1/2– negative families, including not only multiple female bca cases, but also 1 or more members diagnosed with mbc or other cancers
DNA repair and metabolic gene polymorphisms and male breast cancer risk
No full textABSTRACT NOT AVAILABL
- …
