体细胞二代测序面板中包含的遗传性癌症易感基因入门知识

Primer on Hereditary Cancer Predisposition Genes Included Within Somatic Next-Generation Sequencing Panels.

作者信息

Akras Zade, Bungo Brandon, Leach Brandie H, Marquard Jessica, Ahluwalia Manmeet, Carraway Hetty, Grivas Petros, Sohal Davendra P S, Funchain Pauline

机构信息

Cleveland Clinic, Cleveland, OH.

University of Washington, Seattle, WA.

出版信息

JCO Precis Oncol. 2019 Dec;3:1-11. doi: 10.1200/PO.18.00258.

DOI:10.1200/PO.18.00258

PMID:35100683

Abstract

PURPOSE

It has been estimated that 5% to 10% of cancers are due to hereditary causes. Recent data sets indicate that the incidence of hereditary cancer may be as high as 17.5% in patients with cancer, and a notable subset is missed if screening is solely by family history and current syndrome-based testing guidelines. Identification of germline variants has implications for both patients and their families. There is currently no comprehensive overview of cancer susceptibility genes or inclusion of these genes in commercially available somatic testing. We aimed to summarize genes linked to hereditary cancer and the somatic and germline panels that include such genes.

METHODS

Germline predisposition genes were chosen if commercially available for testing. Penetrance was defined as low, moderate, or high according to whether the gene conferred a 0% to 20%, 20% to 50%, or 50% to 100% lifetime risk of developing the cancer or, when percentages were not available, was estimated on the basis of existing literature descriptions.

RESULTS

We identified a total of 89 genes linked to hereditary cancer predisposition, and we summarized these genes alphabetically and by organ system. We considered four germline and six somatic commercially available panel tests and quantified the coverage of germline genes across them. Comparison between the number of genes that had germline importance and the number of genes included in somatic testing showed that many but not all germline genes are tested by frequently used somatic panels.

CONCLUSION

The inclusion of cancer-predisposing genes in somatic variant testing panels makes incidental germline findings likely. Although somatic testing can be used to screen for germline variants, this strategy is inadequate for comprehensive screening. Access to genetic counseling is essential for interpretation of germline implications of somatic testing and implementation of appropriate screening and follow-up.

摘要

目的

据估计，5%至10%的癌症是由遗传因素引起的。最近的数据集表明，癌症患者中遗传性癌症的发病率可能高达17.5%，如果仅通过家族史和当前基于综合征的检测指南进行筛查，会遗漏相当一部分病例。种系变异的鉴定对患者及其家族都有影响。目前尚无关于癌症易感基因的全面概述，也没有将这些基因纳入商业可用的体细胞检测中。我们旨在总结与遗传性癌症相关的基因以及包含此类基因的体细胞和种系检测 panel。

方法

如果有商业可用的检测，则选择种系易感性基因。根据该基因赋予患癌的终生风险为0%至20%、20%至50%或50%至100%，将外显率定义为低、中或高；如果没有百分比数据，则根据现有文献描述进行估计。

结果

我们共鉴定出89个与遗传性癌症易感性相关的基因，并按字母顺序和器官系统对这些基因进行了总结。我们考虑了四种种系和六种体细胞商业可用的panel检测，并对它们覆盖的种系基因进行了量化。具有种系重要性的基因数量与体细胞检测中包含的基因数量之间的比较表明，许多但并非所有种系基因都通过常用的体细胞panel进行检测。