Non-Coding Variants in BRCA1 and BRCA2 Genes: Potential Impact on Breast and Ovarian Cancer Predisposition

被引：19

作者：

dos Santos, Elizabeth Santana ^{[1
,2
,3
]}

Lallemand, Francois ^{[3
,4
]}

Burke, Leslie ^{[5
]}

Stoppa-Lyonnet, Dominique ^{[3
,6
,7
]}

Brown, Melissa ^{[5
]}

Caputo, Sandrine M. ^{[3
,4
]}

Rouleau, Etienne ^{[8
]}

机构：

[1] AC Camargo Canc Ctr, BR-01509010 Sao Paulo, Brazil

[2] Canc Inst State Sao Paulo, ICESP, Ctr Translat Oncol, Dept Oncol, BR-01246000 Sao Paulo, Brazil

[3] Inst Curie, Dept Genet, F-75005 Paris, France

[4] Paris Sci Lettres Res Univ, Inst Curie, F-75230 Paris, France

[5] Univ Queensland, Sch Chem & Mol Biosci, Brisbane, Qld 4072, Australia

[6] Univ Paris 05, Inst Curie, Dept Genet, F-75006 Paris, France

[7] INSERM, Inst Curie, U830, F-75248 Paris, France

[8] Inst Gustave Roussy, F-94805 Villejuif, France

来源：

CANCERS | 2018年 / 10卷 / 11期

关键词：

BRCA1; BRCA2; non-coding variants; promoter; hereditary breast cancer; hereditary ovarian cancer; DOWN-REGULATION; SPLICING ALTERATIONS; MAINTENANCE THERAPY; PROMOTER MUTATIONS; MESSENGER-RNA; SUSCEPTIBILITY; IDENTIFICATION; METHYLATION; RISK; MLH1;

D O I：

10.3390/cancers10110453

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

BRCA1 and BRCA2 are major breast cancer susceptibility genes whose pathogenic variants are associated with a significant increase in the risk of breast and ovarian cancers. Current genetic screening is generally limited to BRCA1/2 exons and intron/exon boundaries. Most identified pathogenic variants cause the partial or complete loss of function of the protein. However, it is becoming increasingly clear that variants in these regions only account for a small proportion of cancer risk. The role of variants in non-coding regions beyond splice donor and acceptor sites, including those that have no qualitative effect on the protein, has not been thoroughly investigated. The key transcriptional regulatory elements of BRCA1 and BRCA2 are housed in gene promoters, untranslated regions, introns, and long-range elements. Within these sequences, germline and somatic variants have been described, but the clinical significance of the majority is currently unknown and it remains a significant clinical challenge. This review summarizes the available data on the impact of variants on non-coding regions of BRCA1/2 genes and their role on breast and ovarian cancer predisposition.

引用

页数：21

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