The prevalence of germline mutations in cancer susceptible genes in patients with early-onset renal cell carcinoma


( In a session of the best kidney cancer poster presentations at this year’s Society of Urologic Oncology (SUO) virtual annual meeting, Dr. Truong presented an assessment of the prevalence of germline mutations in patients with kidney cancer. It has been accepted that approximately one in twenty (5%) of renal cell carcinoma patients have an inherited cause, with an early age at diagnosis (often <46 years) suggested as a criterion for evaluating genetic counseling.

The authors looked at 233 patients at their institution with renal cell carcinoma diagnosed before the age of 46 who agreed to have germline sequencing. Germline testing was performed with a targeted panel of> 76 cancer-associated genes, using an institutional matched tumor germline sequencing protocol (n = 165) or following an evaluation in a clinical genetics clinic (n = 68). The authors evaluated mutational prevalence and spectrum and clinicopathological characteristics based on the mutation status.


Among these 233 patients, the mean age at diagnosis was 38 years (range 21 to 46 years), 39 (17%) had a renal cell carcinoma family, and 34 (15%) had cell-consistent characteristics. renal syndromic carcinoma. 122 of 233 patients (52.4%) had clear cell renal cell carcinoma.

Germinal mutations were identified in 43 patients, representing 19% of the patients evaluated. Of these, 21 patients (9% of the cohort) had mutations in known renal cell carcinoma (genes associated with RCC_ including FH (n = 12), VHL (n = 4), SDHB (n = 2), BAP1 (n = 1), TESC1 (n = 1) and FLCN (n = 1). An additional 11 patients (5% of the cohort) had mutations in moderate / high penetrance non-RCC genes, including BRCA1 (n = 2), TMJ (n = 2), CHEK2 (n = 2), TP53 (n = 2), PALB2 (n = 1) and RET (n = 1).

Of those with known RCC-associated mutations, 11 (52%) had syndromic features, 6 (29%) had a family history of renal cell carcinoma but no syndromic features, and the remainder had neither. . Among patients with known RCC-associated mutations, all patients with clear cell histology had syndromic features or family history, while only 44% of those with unclear cell histology had these features. Seven of the 9 (77.8%) patients with non-RCC genes met the standard criteria for genetic testing.

The authors noted that most patients with unclear cell histology had no family history or syndromic features suggesting underlying genetic causality, while all patients with clear cell histology had these features. The authors conclude that extensive genetic testing, particularly on patients with unclear cell RCC, is warranted in patients with early-onset renal cell carcinoma.

Presented by: Hong Truong, MD, MS, urological oncology fellow at Memorial Sloan Kettering Cancer Center, New York, New York.

Written by: Christopher JD Wallis, MD, Ph.D., Instructor in Urology, Vanderbilt University Medical Center, Nashville, Tennessee @WallisCJD on Twitter at the 2020 Society of Urologic Oncology Annual Meeting – December 2-5, 2020 – Washington, DC

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