Effects of BRCA2 cis-regulation in normal breast and cancer risk amongst BRCA2 mutation carriers

Introduction: Cis-acting regulatory single nucleotide polymorphisms (SNPs) at specific loci may modulate penetrance of germline mutations at the same loci by introducing different levels of expression of the wild-type allele. We have previously reported that BRCA2 shows differential allelic expression and we hypothesize that the known variable penetrance of BRCA2 mutations might be associated with this mechanism. Methods: We combined haplotype analysis and differential allelic expression of BRCA2 in breast tissue to identify expression haplotypes and candidate cis-regulatory variants. These candidate variants underwent selection based on in silico predictions for regulatory potential and di…

Genetic variation at 9p22.2 and ovarian cancer risk for BRCA1 and BRCA2 mutation carriers

[Background]: Germline mutations in the BRCA1 and BRCA2 genes are associated with increased risks of breast and ovarian cancers. Although several common variants have been associated with breast cancer susceptibility in mutation carriers, none have been associated with ovarian cancer susceptibility. A genome-wide association study recently identified an association between the rare allele of the single-nucleotide polymorphism (SNP) rs3814113 (ie, the C allele) at 9p22.2 and decreased risk of ovarian cancer for women in the general population. We evaluated the association of this SNP with ovarian cancer risk among BRCA1 or BRCA2 mutation carriers by use of data from the Consortium of Investi…

Erratum à l’article : « Dépistage du cancer du sein : en route vers le futur » [Bull. Cancer 103 (2016) 753–763]

Dépistage du cancer du sein : en route vers le futur

Breast cancer remains a potentially lethal disease, which requires aggressive treatments and is associated with long-term consequences. Its prognosis is linked to both tumor biology and burden at diagnosis. Although treatments have allowed important improvements in prognosis over the past 20 years, breast cancer screening remains necessary. Mammographic screening allows earlier stage diagnoses and a decrease of breast cancer specific mortality. However, breast cancer screening modalities should be revised with the objective to address demonstrated limitations of mammographic screening (limited benefit, imperfect sensitivity and specificity, overdiagnoses, radiation-induced morbidity). Furth…

A SUMOylation-defective MITF germline mutation predisposes to melanoma and renal carcinoma

International audience; So far, no common environmental and/or phenotypic factor has been associated with melanoma and renal cell carcinoma (RCC). The known risk factors for melanoma include sun exposure, pigmentation and nevus phenotypes; risk factors associated with RCC include smoking, obesity and hypertension. A recent study of coexisting melanoma and RCC in the same patients supports a genetic predisposition underlying the association between these two cancers. The microphthalmia-associated transcription factor (MITF) has been proposed to act as a melanoma oncogene; it also stimulates the transcription of hypoxia inducible factor (HIF1A), the pathway of which is targeted by kidney canc…