Advances in the Diagnosis of Hereditary Kidney Cancer: Initial Results of a Multigene Panel Test

被引:39
作者
Nguyen, Kevin A. [1 ]
Syed, Jamil S. [1 ]
Espenschied, Carin R. [2 ]
LaDuca, Holly [2 ]
Bhagat, Ansh M. [1 ]
Suarez-Sarmiento, Alfredo [1 ]
O'Rourke, Timothy K., Jr. [3 ]
Brierley, Karina L. [4 ]
Hofstatter, Erin W. [5 ]
Shuch, Brian [1 ,6 ]
机构
[1] Yale Sch Med, Dept Urol, POB 208058, New Haven, CT 06520 USA
[2] Ambry Genet, Clin Diagnost, Aliso Viejo, CA USA
[3] Quinnipiac Univ, Frank H Netter MD Sch Med, North Haven, CT USA
[4] Smilow Canc Hosp, Yale Canc Genet & Prevent Program, New Haven, CT USA
[5] Yale Sch Med, Sect Med Oncol, Dept Med, New Haven, CT 06520 USA
[6] Yale Sch Med, Dept Radiol, New Haven, CT 06520 USA
关键词
age of onset; early diagnosis; genetic testing; hereditary; kidney neoplasms; neoplastic syndromes; MEDICAL GENETICS; AMERICAN-COLLEGE; MUTATION; RISK; BREAST; PREDISPOSES; CARCINOMA; VARIANTS; GERMLINE; GENOMICS;
D O I
10.1002/cncr.30893
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
BACKGROUND: Panel testing has been recently introduced to evaluate hereditary cancer; however, limited information is available regarding its use in kidney cancer. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. (c) 2017 American Cancer Society.
引用
收藏
页码:4363 / 4371
页数:9
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