Multicenter Prospective Cohort Study of the Diagnostic Yield and Patient Experience of Multiplex Gene Panel Testing For Hereditary Cancer Risk
Multicenter Prospective Cohort Study of the Diagnostic Yield and Patient Experience of Multiplex Gene Panel Testing For Hereditary Cancer Risk
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DOI：
10.1200/po.18.00217
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发表时间：
2019-03-28
影响因子：
4.6
通讯作者：
Gruber, Stephen B.
中科院分区：
文献类型：
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作者：
Idos, Gregory E.;Kurian, Allison W.;Gruber, Stephen B.
多重基因组检测（MGPT）可同时分析生殖系肿瘤易感基因。患者和方法这项多中心的前瞻性队列研究招募了来自三个癌症遗传学诊所的参与者-南加州大学诺里斯综合癌症中心，洛杉矶县和南加州大学医学中心，和斯坦福大学癌症研究所-符合检测指南或具有2.5%或更高致病性变异概率的患者（N = 2，000）。所有患者均接受25或28基因MGPT，并将结果与预试验专家临床评估产生的差异遗传诊断进行比较。测试后调查的痛苦，不确定性和积极的经验，管理在3个月（69%的响应率）和1年（57%的响应率）。结果2,000名参与者中，81%是女性，41%是西班牙裔，26%是西班牙语只，30%完成高中或更少的教育。共有242名参与者（12%）携带一种或多种致病性变异（阳性），689名（34%）携带一种或多种不确定意义的变异（VUS），1，069名（53%）不携带致病性变异或VUS（阴性）。超过三分之一的致病性变异（34%）未纳入鉴别诊断。测试后，很少有患者（4%）进行了预防性手术，大多数（92%）从不后悔测试，大多数（80%）想知道所有的结果，即使是那些不确定的意义。阳性患者是阴性/VUS患者的两倍（83%v 41%; P < .001），以鼓励他们的亲属进行tested.CONCLUSION在种族/民族和社会经济多样化的队列，MGPT增加诊断率。超过三分之一的已确定致病性变异不是临床预期的。患者后悔和预防性手术的使用率较低，患者适当地鼓励亲属接受临床相关结果的检测。(C)2018年美国临床肿瘤学会
PURPOSE Multiplex gene panel testing (MGPT) allows for the simultaneous analysis of germline cancer susceptibility genes. This study describes the diagnostic yield and patient experiences of MGPT in diverse populations.PATIENTS AND METHODS This multicenter, prospective cohort study enrolled participants from three cancer genetics clinics-University of Southern California Norris Comprehensive Cancer Center, Los Angeles County and University of Southern California Medical Center, and Stanford Cancer Institute-who met testing guidelines or had a 2.5% or greater probability of a pathogenic variant (N = 2,000). All patients underwent 25- or 28-gene MGPT and results were compared with differential genetic diagnoses generated by pretest expert clinical assessment. Post-test surveys on distress, uncertainty, and positive experiences were administered at 3 months (69% response rate) and 1 year (57% response rate).RESULTS Of 2,000 participants, 81% were female, 41% were Hispanic, 26% were Spanish speaking only, and 30% completed high school or less education. A total of 242 participants (12%) carried one or more pathogenic variant (positive), 689 (34%) carried one or more variant of uncertain significance (VUS), and 1,069 (53%) carried no pathogenic variants or VUS (negative). More than one third of pathogenic variants (34%) were not included in the differential diagnosis. After testing, few patients (4%) had prophylactic surgery, most (92%) never regretted testing, and most (80%) wanted to know all results, even those of uncertain significance. Positive patients were twice as likely as negative/VUS patients (83% v 41%; P < .001) to encourage their relatives to be tested.CONCLUSION In a racially/ethnically and socioeconomically diverse cohort, MGPT increased diagnostic yield. More than one third of identified pathogenic variants were not clinically anticipated. Patient regret and prophylactic surgery use were low, and patients appropriately encouraged relatives to be tested for clinically relevant results. (C) 2018 by American Society of Clinical Oncology