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Cancer. 2017 Nov 15;123(22):4363-4371. doi: 10.1002/cncr.30893. Epub 2017 Aug 8.

Advances in the diagnosis of hereditary kidney cancer: Initial results of a multigene panel test.

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Department of Urology, Yale School of Medicine, New Haven, Connecticut.
Clinical Diagnostics, Ambry Genetics, Aliso Viejo, California.
Frank H. Netter MD School of Medicine at Quinnipiac University, North Haven, Connecticut.
Yale Cancer Genetics and Prevention Program, Smilow Cancer Hospital, New Haven, Connecticut.
Department of Medicine, Section of Medical Oncology, Yale School of Medicine, New Haven, Connecticut.
Department of Radiology, Yale School of Medicine, New Haven, Connecticut.



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.


age of onset; early diagnosis; genetic testing; hereditary; kidney neoplasms; neoplastic syndromes

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