肿瘤测序时代的遗传咨询与胚系检测：一项队列研究
Genetic Counseling and Germline Testing in the Era of Tumor Sequencing: A Cohort Study.
作者信息
Klek Stefan, Heald Brandie, Milinovich Alex, Ni Ying, Abraham Jame, Mahdi Haider, Estfan Bassam, Khorana Alok A, Bolwell Brian J, Grivas Petros, Sohal Davendra P S, Funchain Pauline
机构信息
Loyola University Chicago Stritch School of Medicine, Maywood, IL, USA.
Cleveland Clinic Foundation, Taussig Cancer Institute, Cleveland, OH, USA.
出版信息
JNCI Cancer Spectr. 2020 Mar 5;4(3):pkaa018. doi: 10.1093/jncics/pkaa018. eCollection 2020 Jun.
BACKGROUND
The clinical impact of addressing potential germline alterations from tumor-only next-generation sequencing (NGS) is not well characterized. Current guidelines for cancer genetic testing may miss clinically actionable germline changes, which may have important implications for cancer screening, treatment, and prevention. We examined whether increasing involvement of the clinical genetics service during somatic tumor-only NGS review at Molecular Tumor Board (MTB) increases the detection of germline findings.
METHODS
In a retrospective evaluation of patients who underwent tumor-only NGS and were reviewed at MTB, we quantified genetic counseling (GC) referrals as well as germline testing uptake and results across three cohorts: before (C1) and after (C2) the addition of tumor-only NGS review and after (C3) instituting a formal process to coordinate NGS-based genetics referrals to preexisting oncology appointments. All statistical tests were two-sided.
RESULTS
From 2013 to 2017, 907 tumor-only NGS reports were reviewed at MTB (n = 281, n = 493, n = 133); gastrointestinal (22.5%), lung (19.7%), genitourinary (14.8%), and breast (14.1%) were the most common index cancers. GC visits due to MTB increased with each successive cohort (C1 = 1.1%, C2 = 6.9%, C3 = 13.5%; for trend [ ] < .001), as did germline testing (C1 = 0.7%, C2 = 3.2%, C3 = 11.3%; < .001). Diagnosis of germline pathogenic variants increased with each successive cohort (C1 = 1.4%, C2 = 2.0%, C3 = 7.5%; = .003) and with germline pathogenic variants found by MTB review (C1 = 0.4%, C2 = 0.4%, C3 = 2.3%; = .12).
CONCLUSIONS
Both review of tumor-only NGS by genetics and the institution of a process coordinating GC with oncology appointments increased the discovery of germline pathogenic variants from tumor-only NGS testing. Furthermore, this process identified germline pathogenic variant carriers who would not have otherwise met standard criteria for germline testing.
背景
仅通过肿瘤下一代测序（NGS）来检测潜在的种系改变，其临床影响尚未得到充分表征。目前的癌症基因检测指南可能会遗漏具有临床可操作性的种系改变，这可能对癌症筛查、治疗和预防具有重要意义。我们研究了在分子肿瘤委员会（MTB）仅对体细胞肿瘤进行NGS评估期间，增加临床遗传学服务的参与是否能提高种系改变的检出率。
方法
在一项对接受仅肿瘤NGS检测并在MTB进行评估的患者的回顾性评估中，我们对三个队列中的遗传咨询（GC）转诊以及种系检测的接受情况和结果进行了量化：在仅肿瘤NGS评估增加之前（C1）和之后（C2），以及在建立一个正式流程以协调基于NGS的遗传学转诊与现有的肿瘤学预约之后（C3）。所有统计检验均为双侧检验。
结果
2013年至2017年，MTB共评估了907份仅肿瘤的NGS报告（n = 281、n = 493、n = 133）；最常见的索引癌症为胃肠道癌（22.5%）、肺癌（19.7%）、泌尿生殖系统癌（14.8%）和乳腺癌（14.1%）。因MTB而进行的GC就诊在每个连续队列中均增加（C1 = 1.1%，C2 = 6.9%，C3 = 13.5%；趋势检验P <.001），种系检测情况也是如此（C1 = 0.7%，C2 = 3.2%，C3 = 11.3%；P <.001）。种系致病变异的诊断在每个连续队列中均增加（C1 = 1.4%，C2 = 2.0%，C3 = 7.5%；P = .003），并且与MTB评估发现的种系致病变异有关（C1 = 0.4%，C2 = 0.4%，C3 = 2.3%；P = .12）。
结论
遗传学对仅肿瘤NGS的评估以及建立将GC与肿瘤学预约协调起来的流程，均增加了从仅肿瘤NGS检测中发现种系致病变异的几率。此外，这一流程还识别出了那些原本不符合种系检测标准的种系致病变异携带者。
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