Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston.
Tempus Labs Inc, Chicago, Illinois.
JAMA Netw Open. 2022 May 2;5(5):e2213070. doi: 10.1001/jamanetworkopen.2022.13070.
Germline testing guidelines are suggested for specific disease types or a family history of cancer, yet alterations are found in cancer types in which germline testing is not routinely indicated. The clinical role of identifying germline variants in these populations is valuable to patients and their at-risk relatives.
To evaluate the prevalence of germline findings in patients undergoing tumor/normal matched sequencing among cancer types lacking guidelines.
DESIGN, SETTING, AND PARTICIPANTS: This retrospective cross-sectional study took place on August 18, 2021, and included data from deidentified records of patients tested, using the Tempus xT tumor/normal matched approach from November 2017 to August 2021. Records included in this study were from 34 642 patients treated in geographically diverse oncology practices in the US with a diagnosis of any of the following cancers: bladder, brain, lung, esophagus, cholangiocarcinoma, head and neck, breast, ovarian, pancreatic, prostate, endometrial, and colorectal.
The rate of germline findings (ie, single-nucleotide variants and small insertions or deletions) detected in 50 reportable hereditary cancer genes was calculated for cancer types lacking guidelines for germline testing (bladder, brain, lung, esophagus, cholangiocarcinoma, and head and neck) and cancer types for which germline testing is frequently performed (breast, ovarian, pancreatic, prostate, endometrial, and colorectal). Same-gene second somatic hits were assessed to provide a comprehensive assessment on genomic drivers.
Of 34 642 patients, 18 888 were female (54.5%); of 27 498 patients whose age at diagnosis was known, mean (SD) age was 62.23 (3.36) years. A total of 2534 of 34 642 patients (7.3%) harbored pathogenic or likely pathogenic germline variants. Within the tumor types lacking testing guidelines, germline mutations were at 6.6% (79/1188) in bladder cancer and 5.8% (448/7668) in lung cancer.
This study may present the largest retrospective analysis to date of deidentified real-world data from patients diagnosed with advanced cancer with tumor/normal matched sequencing data and the prevalence of pathogenic or likely pathogenic germline variants in cancer types lacking hereditary cancer testing guidelines. The findings suggest there may be clinical implications for patients and their at-risk family members in cancers for which germline assessment primarily based on the cancer diagnosis is rarely obtained.
胚系检测指南针对特定疾病类型或癌症家族史建议，但在常规不建议胚系检测的癌症类型中也发现了改变。在这些人群中确定胚系变异的临床作用对患者及其高危亲属是有价值的。
评估在缺乏指南的癌症类型中，接受肿瘤/正常匹配测序的患者中胚系检测结果的发生率。
设计、设置和参与者：这是一项回顾性横断面研究，于 2021 年 8 月 18 日进行，纳入了 2017 年 11 月至 2021 年 8 月期间使用 Tempus xT 肿瘤/正常匹配方法检测的患者的匿名记录数据。本研究中的记录来自美国地理上多样化的肿瘤学实践中诊断为以下任何一种癌症的 34642 名患者：膀胱癌、脑癌、肺癌、食管癌、胆管癌、头颈部癌、乳腺癌、卵巢癌、胰腺癌、前列腺癌、子宫内膜癌和结直肠癌。
对于缺乏胚系检测指南的癌症类型（膀胱癌、脑癌、肺癌、食管癌、胆管癌和头颈部癌）和经常进行胚系检测的癌症类型（乳腺癌、卵巢癌、胰腺癌、前列腺癌、子宫内膜癌和结直肠癌），计算在 50 个可报告的遗传性癌症基因中检测到的胚系检测结果（单核苷酸变异和小插入或缺失）的发生率。评估相同基因的第二次体细胞突变，以提供对基因组驱动因素的全面评估。
在 34642 名患者中，1888 名（54.5%）为女性；在已知诊断时年龄的 27498 名患者中，平均（SD）年龄为 62.23（3.36）岁。在 34642 名患者中，共有 2534 名（7.3%）携带致病性或可能致病性的胚系变异。在缺乏检测指南的肿瘤类型中，膀胱癌的胚系突变率为 6.6%（79/1188），肺癌为 5.8%（448/7668）。
本研究可能是迄今为止对接受肿瘤/正常匹配测序的晚期癌症患者的匿名真实世界数据进行的最大回顾性分析，以及缺乏遗传性癌症检测指南的癌症类型中致病性或可能致病性胚系变异的发生率。研究结果表明，在主要基于癌症诊断很少获得胚系评估的癌症中，可能对患者及其高危家庭成员具有临床意义。
