TY - JOUR

T1 - Hereditary breast and ovarian cancer

T2 - new genes in confined pathways

AU - Nielsen, Finn Cilius

AU - Hansen, Thomas van Overeem

AU - Sørensen, Claus Storgaard

PY - 2016/9

Y1 - 2016/9

N2 - Genetic abnormalities in the DNA repair genes BRCA1 and BRCA2 predispose to hereditary breast and ovarian cancer (HBOC). However, only approximately 25% of cases of HBOC can be ascribed to BRCA1 and BRCA2 mutations. Recently, exome sequencing has uncovered substantial locus heterogeneity among affected families without BRCA1 or BRCA2 mutations. The new pathogenic variants are rare, posing challenges to estimation of risk attribution through patient cohorts. In this Review article, we examine HBOC genes, focusing on their role in genome maintenance, the possibilities for functional testing of putative causal variants and the clinical application of new HBOC genes in cancer risk management and treatment decision-making.

AB - Genetic abnormalities in the DNA repair genes BRCA1 and BRCA2 predispose to hereditary breast and ovarian cancer (HBOC). However, only approximately 25% of cases of HBOC can be ascribed to BRCA1 and BRCA2 mutations. Recently, exome sequencing has uncovered substantial locus heterogeneity among affected families without BRCA1 or BRCA2 mutations. The new pathogenic variants are rare, posing challenges to estimation of risk attribution through patient cohorts. In this Review article, we examine HBOC genes, focusing on their role in genome maintenance, the possibilities for functional testing of putative causal variants and the clinical application of new HBOC genes in cancer risk management and treatment decision-making.

KW - Journal Article

U2 - 10.1038/nrc.2016.72

DO - 10.1038/nrc.2016.72

M3 - Review

C2 - 27515922

VL - 16

SP - 599

EP - 612

JO - Nature Reviews. Cancer

JF - Nature Reviews. Cancer

SN - 1474-175X

IS - 9

ER -