Clinical testing with a panel of 25 genes associated with increased cancer risk results in a significant increase in clinically significant findings across a broad range of cancer histories
Clinical testing with a panel of 25 genes associated with increased cancer risk results in a significant increase in clinically significant findings across a broad range of cancer histories
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DOI：
10.1016/j.cancergen.2017.09.003
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发表时间：
2017-12-01
期刊：
影响因子：
1.9
通讯作者：
Manley, Susan
中科院分区：
文献类型：
--
作者：
Rosenthal, Eric T.;Bernhisel, Ryan;Manley, Susan
遗传性癌症风险的基因检测现在被广泛用于筛查和预防的目标个体。然而，有有限的证据可用于评估各种检测策略的临床效用，如单一综合征，单一癌症或泛癌症基因面板。在这里，我们报告了在2013年9月至2016年7月期间对252，223名个体进行的25个基因泛癌症面板测试的结果。大多数个体（92.8%）符合遗传性乳腺癌和卵巢癌（HBOC）和/或Lynch综合征（LS）的检测标准。总体而言，在17，000名（6.7%）受试者中确定了17，340例PV。PV阳性率在有个人癌症史的个体中为9.8%，而未受影响的个体为4.7%。PV在BRCA 1/2（42.2%）、其他乳腺癌（BR）基因（32.9%）和LS基因（13.2%）中最常见。在仅符合HBOC检测标准的个体中发现的PV中有一半是BRCA 1/2以外的基因。同样，在仅符合LS检测标准的个体中发现的PV中有一半是非LS基因。这些发现表明，在该队列中使用泛癌症面板进行基因检测比传统的单基因或单综合征检测提供了更好的临床实用性。
Genetic testing for inherited cancer risk is now widely used to target individuals for screening and prevention. However, there is limited evidence available to evaluate the clinical utility of various testing strategies, such as single-syndrome, single-cancer, or pan-cancer gene panels. Here we report on the outcomes of testing with a 25-gene pan-cancer panel in a consecutive series of 252,223 individuals between September 2013 and July 2016. The majority of individuals (92.8%) met testing criteria for Hereditary Breast and Ovarian Cancer (HBOC) and/or Lynch syndrome (LS). Overall, 17,340 PVs were identified in 17,000 (6.7%) of the tested individuals. The PV positive rate was 9.8% among individuals with a personal cancer history, compared to 4.7% in unaffected individuals. PVs were most common in BRCA1/2 (42.2%), other breast cancer (BR) genes (32.9%), and the LS genes (13.2%). Half the PVs identified among individuals who met only HBOC testing criteria were in genes other than BRCA1/2. Similarly, half of PVs identified in individuals who met only LS testing criteria were in non-LS genes. These findings suggest that genetic testing with a pan-cancer panel in this cohort provides improved clinical utility over traditional single-gene or single-syndrome testing.