Genetic aspects of hereditary breast and ovarian cancer: options and limits

被引：5

作者：

Meindl, Alfons ^{[1
]}

Ramser, Juliane ^{[1
]}

Hauke, Jan ^{[2
,3
]}

Hahnen, Eric ^{[2
,3
]}

机构：

[1] TU, Klinikum Rechts Isar, Frauenklin, Abt Gyn Tumorgenet, D-81675 Munich, Germany

[2] Univ Klinikum Koln, Zentrum Familiarer Brust & Eierstockkrebs, Cologne, Germany

[3] Ctr Integrierte Onkol CIO Koln Bonn, Bonn, Germany

来源：

MEDIZINISCHE GENETIK | 2015年 / 27卷 / 02期

关键词：

Hereditary breast and ovarian cancer; Panel diagnostics; Risk genes; Multigene analysis; GERMLINE MUTATIONS; SUSCEPTIBILITY LOCI; FAMILY-HISTORY; FALLOPIAN-TUBE; EARLY-ONSET; RISK; VARIANTS; PALB2; PATIENT; RAD51D;

D O I：

10.1007/s11825-015-0048-0

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Recent studies have documented the genetic heterogeneity of familial breast and ovarian cancer. In addition to BRCA1 and BRCA2, more than 20 risk genes for hereditary breast and ovarian cancer, explaining about one third of familial cases, have been identified so far. Additionally, polygenic factors have been discovered that may explain about 16 % of the genetic burden of BRCA1/2-negative cases. Today, routine diagnostics using gene panels in addition to BRCA1/2 testing is already offered in many countries, but sufficient information is available for only a few of the genes analyzed. Therefore, the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC) compiled the TruRisk (TM) 34-gene panel, which contains 10 so-called "core genes" (ATM, BRCA1, BRCA2, CDH1, CHEK2, NBN, PALB2, RAD51C, RAD51D, TP53) in addition to 24 candidate genes. For members of the GC-HBOC, the analysis of the 10 core genes is obligatory. In addition to the TruRisk (TM) panel, several other gene panels are commercially available, e.g., the TruSight Cancer Panel (Illumina), which covers 94 genes, or the BRCA Hereditary Cancer MASTR(TM) Plus (Multiplicom) and Myriad MyRisk(TM) (Myriad Genetics), which comprise 26 genes each. All these gene panels include the core genes and are also applied in Germany.The use of panel diagnostics in the setting of molecular genetic testing for tumor predisposition disorders allows a reliable and flexible analysis of relevant risk factors. In contrast, exome or even whole genome sequencing is a powerful method of identifying further candidates quickly and cheaply. However, the determination of clinical consequences for mutations in novel genes requires comprehensive national and international validation studies.

引用

页码：202 / +

页数：8

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