Evaluation of a 27-gene inherited cancer panel across 630 consecutive patients referred for testing in a clinical diagnostic laboratory.
Evaluation of a 27-gene inherited cancer panel across 630 consecutive patients referred for testing in a clinical diagnostic laboratory.
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DOI：
10.1186/s13053-017-0083-8
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发表时间：
2018
影响因子：
1.7
通讯作者：
Nagan N
中科院分区：
文献类型：
--
作者：
Gardner SA;Weymouth KS;Kelly WS;Bogdanova E;Chen W;Lupu D;Suhl J;Zeng Q;Geigenmüller U;Boles D;Okamoto PM;McDowell G;Hayden MA;Nagan N
遗传性癌症的广泛临床和遗传异质性使得多基因面板检测成为一种有效的方法，用于识别具有广泛的综合征和非综合征型癌症遗传易感性的患者。本研究报告了我们在630个连续个体的队列中进行27个基因遗传癌症小组的经验，这些个体被转介到我们的实验室进行测试，目的如下：确定与近期文献发表的数据相关的阳性病例和具有不确定临床意义变异（VUS）的病例的比率2。2 .检查面板上组成基因的异质性；回顾该队列的检测吸收情况，并与其他描述扩展组检测结果的报告进行比较。对630名个体的临床和基因组数据进行了回顾，这些个体的27个基因是根据遗传性癌症终生高（≥40%）或中低（≤40%）风险选择的。这些患者不符合遗传性乳腺癌和卵巢癌（HBOC）或Lynch综合征（LS）的国家综合癌症网络（NCCN）标准，并构成转诊实验室队列。65个个体在14个基因中被鉴定为致病性或可能致病性变异，总阳性率为10.3%。虽然癌症家族史是转诊的主要原因，占我们队列的84%，但排除已知家族变异的患者对观察到的阳性率没有显著影响（9%对10.3%）。超过一半（58%）的致病性或可能致病性变异在该小组的高或中至低风险基因中观察到，而仅42%发生在经典HBOC或ls相关基因中。这些结果提供了家庭或个人癌症病史的实际百分比，可归因于我们小组中一个或多个基因的致病性或可能致病性变异，并证实了多基因小组在序列测试中识别具有遗传易感性的个体的效用。本文的在线版本（doi: 10.1186/s13053-017-0083-8）包含补充资料，仅供授权用户使用。
Extensive 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. Clinical 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. Sixty-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. These 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. The online version of this article (doi: 10.1186/s13053-017-0083-8) contains supplementary material, which is available to authorized users.
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DOI：
10.1038/modpathol.2016.135
发表时间：
2016-11
期刊：
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
影响因子：
--
作者：
Ring KL;Bruegl AS;Allen BA;Elkin EP;Singh N;Hartman AR;Daniels MS;Broaddus RR
通讯作者：
Broaddus RR
来自1,092个人基因组的遗传变异的综合图。
影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1038/gim.2014.40
发表时间：
2014-11
期刊：
Genetics in medicine : official journal of the American College of Medical Genetics
影响因子：
--
作者：
通讯作者：
--
影响因子：
--
作者：
Apostolou P;Fostira F
通讯作者：
Fostira F
影响因子：
4.6
作者：
Aziz, Nazneen;Zhao, Qin;Voelkerding, Karl V.
通讯作者：
Voelkerding, Karl V.