Nguyen Kevin A, Syed Jamil S, Espenschied Carin R, LaDuca Holly, Bhagat Ansh M, Suarez-Sarmiento Alfredo, O'Rourke Timothy K, Brierley Karina L, Hofstatter Erin W, Shuch Brian
Department of Urology, Yale School of Medicine, New Haven, Connecticut.
Clinical Diagnostics, Ambry Genetics, Aliso Viejo, California.
Cancer. 2017 Nov 15;123(22):4363-4371. doi: 10.1002/cncr.30893. Epub 2017 Aug 8.
Panel testing has been recently introduced to evaluate hereditary cancer; however, limited information is available regarding its use in kidney cancer.
The authors retrospectively reviewed test results and clinical data from patients who underwent targeted multigene panel testing of up to 19 genes associated with hereditary kidney cancer from 2013 to 2016. The frequency of positive (mutation/variant likely pathogenic), inconclusive (variant of unknown significance), and negative results was evaluated. A logistic regression analysis evaluated predictive factors for a positive test.
Patients (n = 1235) had a median age at diagnosis of 46 years, which was significantly younger than the US population of individuals with kidney cancer (P < .0001). Overall, 6.1%, 75.5%, and 18.4% of individuals had positive, negative, and inconclusive results, respectively. The most commonly altered genes included folliculin (FLCN) and fumarate hydratase (FH), which were altered in 1.8% and 1.3% of patients, respectively. Tuberous Sclerosis Complex 2 (TSC2), mesenchymal epithelial transition factor proto-oncogene (MET), and PMS1 homolog 2 (PMS2) had the highest rates of variants of unknown significance, which were identified in 2.7%, 2.2%, and 1.7% of patients, respectively. Early age of onset was the only factor that was identified as predictive of a positive test on multivariate analysis (odds ratio, 0.975; P = .0052) and may be the only identifying characteristic of low-penetrant syndromes, such as those associated with MITF (melanogenesis-associated transcription factor) mutations, which do not have singular histology or a family history of kidney cancer.
Panel tests may be particularly useful for patients who lack distinguishing clinical characteristics of known hereditary kidney cancer syndromes. The current results support the use of early age of onset for genetic counseling and/or testing. Cancer 2017;123:4363-71. © 2017 American Cancer Society.
基因组合检测最近被用于评估遗传性癌症；然而，关于其在肾癌中的应用的信息有限。
作者回顾性分析了2013年至2016年间接受多达19个与遗传性肾癌相关基因的靶向多基因组合检测的患者的检测结果和临床数据。评估了阳性（突变/可能致病的变异）、不确定（意义不明的变异）和阴性结果的频率。进行逻辑回归分析以评估检测呈阳性的预测因素。
患者（n = 1235）诊断时的中位年龄为46岁，显著低于美国肾癌患者人群（P <.0001）。总体而言，分别有6.1%、75.5%和18.4%的个体检测结果为阳性、阴性和不确定。最常发生改变的基因包括卵泡抑素（FLCN）和延胡索酸水合酶（FH），分别在1.8%和1.3%的患者中发生改变。结节性硬化症复合物2（TSC2）、间充质上皮转化因子原癌基因（MET）和PMS1同源物2（PMS2）的意义不明的变异率最高，分别在2.7%、2.2%和1.7%的患者中被鉴定出来。发病年龄早是多变量分析中唯一被确定为检测呈阳性的预测因素（比值比，0.975；P = 0.0052），可能是低外显率综合征的唯一识别特征，如与小眼畸形相关转录因子（MITF）突变相关的综合征，这些综合征没有单一的组织学特征或肾癌家族史。
基因组合检测对于缺乏已知遗传性肾癌综合征特征性临床特点的患者可能特别有用。目前的结果支持将发病年龄早用于遗传咨询和/或检测。癌症2017；123：4363 - 71。© 2017美国癌症协会。
