BackgroundExtensive clinical and genetic heterogeneity of inherited cancers has allowed multi-gene panel testing to become an efficient means for identification of patients with an inherited predisposition to a broad spectrum of syndromic and nonsyndromic forms of cancer. This study reports our experience with a 27-gene inherited cancer panel on a cohort of 630 consecutive individuals referred for testing at our laboratory with the following objectives: 1. Determine the rates for positive cases and those with variants of uncertain clinical significance (VUS) relative to data published in the recent literature, 2. Examine heterogeneity among the constituent genes on the panel, and 3. Review test uptake in the cohort relative to other reports describing outcomes for expanded panel testing.MethodsClinical and genomic data were reviewed on 630 individuals tested on a panel of 27 genes selected on the basis of high (≥ 40%) or moderate to low (≤ 40%) lifetime risk of hereditary cancer. These patients were not enriched for adherence to the National Comprehensive Cancer Network (NCCN) criteria for Hereditary Breast and Ovarian Cancer (HBOC) or Lynch Syndrome (LS) and constitute a referral laboratory cohort.ResultsSixty-five individuals with variants classified as pathogenic or likely pathogenic across 14 genes were identified for an overall positive rate of 10.3%. Although a family history of cancer constituted a major reason for referral, accounting for 84% of our cohort, excluding patients with a known familial variant did not have a significant impact on the observed positive rate (9% vs 10.3%). More than half (58%) of the pathogenic or likely pathogenic variants were observed in high or moderate to low risk genes on the panel, while only 42% occurred in classic HBOC or LS-associated genes.ConclusionThese results provide the actual percentage of family or personal history of cancer that can be attributed to pathogenic or likely pathogenic variants in one or more of the genes on our panel and corroborate the utility of multi-gene panels over sequential testing to identify individuals with an inherited predisposition to cancer.

中文翻译：

---

对 630 名连续患者的 27 基因遗传性癌症小组进行评估，这些患者被转诊到临床诊断实验室进行检测

背景遗传性癌症的广泛临床和遗传异质性使多基因组检测成为识别具有遗传易感性的患者对广泛的综合征和非综合征形式癌症的有效手段。本研究报告了我们对一组 630 名连续个体的 27 基因遗传性癌症小组的经验，这些个体被推荐到我们的实验室进行检测，其目标如下： 1. 确定阳性病例和具有不确定临床意义 (VUS) 变异的病例的发生率相对于最近文献中发表的数据， 2. 检查小组中组成基因之间的异质性，以及 3. 相对于描述扩展小组测试结果的其他报告，审查队列中的测试吸收。方法回顾了 630 名个体的临床和基因组数据，这些个体对一组 27 个基因进行了测试，这些基因是根据遗传性癌症的高（≥ 40%）或中低（≤ 40%）终生风险选择的。这些患者并未因遵守国家综合癌症网络 (NCCN) 遗传性乳腺癌和卵巢癌 (HBOC) 或林奇综合征 (LS) 标准而得到丰富，并构成了转诊实验室队列。 结果 65 名个体变异被归类为致病性或可能对 14 个基因的致病性进行了鉴定，总阳性率为 10.3%。尽管癌症家族史是转诊的主要原因，占我们队列的 84%，但排除已知家族性变异的患者对观察到的阳性率没有显着影响（9% 对 10.3%）。