(UroToday.com) 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 patients with renal cell carcinoma have a hereditary cause, with early age at diagnosis (often <46 years of age) suggested as a criterion for genetic counseling assessment.
The authors examined 233 patients at their institution who had renal cell carcinoma diagnosed prior to the age of 46 years who agreed to have germline sequencing. Germline testing was performed with a targeted panel of >76 cancer-associated genes, using either an institutional protocol of matched tumor-germline sequencing (n=165) or following an assessment in a clinical genetics clinic (n=68). The authors assessed mutational prevalence and spectrum and clinicopathologic characteristics according to mutation status.
Among these 233 patients, the mean age at the time of diagnosis was 38 years (range 21 to 46 years), 39 (17%) had a family of renal cell carcinoma, and 34 (15%) had features consistent with syndromic renal cell carcinoma. 122 of 233 (52.4%) patients had clear cell renal cell carcinoma.
Germline mutations were identified in 43 patients, representing 19% of assessed patients. Of these, 21 patients (9% of the cohort) had mutations in known renal cell carcinoma (RCC_-associated genes including FH (n=12), VHL (n=4), SDHB (n=2), BAP1 (n=1), TESC1 (n=1), and FLCN (n=1). A further 11 patients (5% of the cohort) had mutations in moderate/high penetrance non-RCC genes including BRCA1 (n=2), ATM (n=2), CHEK2 (n=2), TP53 (n=2), PALB2 (n=1), and RET (n=1).
Among those with known RCC-associated mutations, 11 (52%) had syndromic features, 6 (29%) had a family history of renal cell carcinoma but not syndromic features, and the remaining 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 non-clear cell histology had these features. Seven of 9 (77.8%) patients with non-RCC genes met standard criteria for genetic testing.
The authors noted that most patients with non-clear cell histology had no family history or syndromic features suggesting underlying genetic causality, while all patients with clear cell histology had these characteristics. The authors conclude that broad genetic testing, particularly of patients with non-clear cell RCC, is warranted in patients with early-onset kidney cancer.
Presented by: Hong Truong, MD, MS, Urologic oncology fellow at Memorial Sloan Kettering Cancer Center, New York, New York.