Exploration of Chinese early-onset renal cancer predisposed genetic features.

Abstract

e17087 Background: The population of early-onset renal cancer patients is increasing in China and they need early genetic screening test to give risks management. In order to avoid the bias of focusing on the patients younger than 45 years old without comparing the genetic features of the patients over 45y and to find more biomarkers, we explored both germline and somatic variations of patients without age limitation. Methods: Ages at confirmed diagnoses and renal tissue samples were collected from 701 patients. The next generation sequencing (NGS) was performed using validated commercial panels containing over 300 genes or WES. Variations were classified into four groups: germline-MUT/ VLM (pathogenic or very like pathogenic mutations), germline-VOUS (variations of unknown significance), somatic-MUT/ VLM and somatic-VOUS. Statistical analysis was performed by t-test (single tail), and p≤ 0.05 was considered statistically significant. Results: In 701 renal cancer patients, with the median age of 55 (12, 86) years old, 114 (16.26%) patients confirmed diagnoses under 45y. The germline MUT/ VLM of 21 genes (FH, VHL, CHEK2, BRCA2, FLCN, ATM, TSC2, SDHB, MUTYH, SDHA, FANCA, RAD50, APC, BARD1, JAK2, LRP1B, TP53, FANCD2, PALB2, MSH6 and CDH1) were observed, more than previous studies. As two aggressive potential predisposed genes in early-onset renal cancer, VHL and FH were studied comprehensively. There were 29 (4.14%) and 369 (52.6%) patients carried FH variations and VHL variations (either germline or somatic), respectively. The median age of patients harbored VHL germline MUT/ VLM was 33.5 (23, 52), significantly lower than other groups (Table). Interestingly, in 6 patients harboring VHL germline MUT/ VLM, 3 of them carried large region deletion. The median age of FH germline-MUT/ VLM group was 33 (21, 59), significantly lower than patients carried germline VOUS (Table). In addition, germline variations or copy number variations of SDHB gene or germline variations of FLCN gene might be associated with early onset. However, the patients No. was small to give conclusion. Conclusions: Genetic test of FH and VHL genes might be necessary in early screening of renal cancer in China. The role of variations of SDHB and FLCN genes and large region deletion needs more explorations. [Table: see text]