Hermel David J, McKinnon Wendy C, Wood Marie E, Greenblatt Marc S
Department of Medicine and University of Vermont Cancer Center, University of Vermont College of Medicine, 89 Beaumont Ave, Given E214, Burlington, VT, 05405, USA.
Fam Cancer. 2017 Jan;16(1):159-166. doi: 10.1007/s10689-016-9913-5.
This study explores our Familial Cancer Program's experience implementing multi-gene panel testing in a largely rural patient population. We conducted a retrospective review of patients undergoing panel testing between May 2011 and August 2015. Our goal was to evaluate factors that might be predictors of identifying variants (pathogenic or uncertain significance) and to assess clinical management changes due to testing. We utilized a structured family history tool to determine the significance of patient's family histories with respect to identification of genetic variants. A total of 227 patients underwent panel testing at our center and 67 patients (29.5 %) had variants identified, with 8 (3.5 %) having multiple variants. Overall, 44 patients (19.4 %) had a variant of uncertain significance (VUS) and 28 patients (12.3 %) had a pathogenic variant detected, with 10 (4.4 %) having pathogenic variants in highly penetrant genes. We found no statistical difference in patient familial and personal cancer history, age, rural status, Ashkenazi Jewish ancestry, insurance coverage and prior single-gene testing among those with pathogenic, VUS and negative panel testing results. There were no predictors of pathogenic variants on regression analysis. Panel testing changed cancer screening and management guidelines from that expected based on family history alone in 13.2 % of patients. Ultimately, cancer panel testing does yield critical information not identified by traditional single gene testing but maximal utility through a broad range of personal and family histories requires improved interpretation of variants.
本研究探讨了我们的家族性癌症项目在主要为农村患者群体中实施多基因检测的经验。我们对2011年5月至2015年8月期间接受基因检测的患者进行了回顾性研究。我们的目标是评估可能预测识别变异（致病性或意义不明确）的因素，并评估检测导致的临床管理变化。我们使用了一种结构化的家族史工具来确定患者家族史对于识别基因变异的意义。共有227名患者在我们中心接受了基因检测，67名患者（29.5%）检测到变异，其中8名（3.5%）有多个变异。总体而言，44名患者（19.4%）有意义不明确的变异（VUS），28名患者（12.3%）检测到致病性变异，其中10名（4.4%）在高穿透性基因中有致病性变异。我们发现，在致病性、VUS和基因检测结果为阴性的患者中，其家族和个人癌症史、年龄、农村身份、阿什肯纳兹犹太血统、保险覆盖范围和既往单基因检测方面没有统计学差异。回归分析中没有致病性变异的预测因素。基因检测改变了13.2%患者仅基于家族史预期的癌症筛查和管理指南。最终，癌症基因检测确实能产生传统单基因检测未发现的关键信息，但要通过广泛的个人和家族史实现最大效用，需要改进对变异的解读。
