Targeted genomic landscape of metastases compared to primary tumours in clear cell metastatic renal cell carcinoma

• DOI: 10.1038/s41416-018-0064-3
• Publication Date: 2018-04-18T16:33:08Z
• Authors: Guillermo de Velasco; Stephanie A. Wank...; Russell Madison; Siraj M. Ali; Craig Norton; Audrey Duquette; Jeffrey S. Ross; Dominick Bossé; Aly-Khan A. Lalani; Vincent A. Miller; Philip J. Stephens; Lauren Young; A. Ari Hakimi; Sabina Signoretti; Sumanta K. Pal; Toni K. Choueiri
• Keywords: Adult; Aged, 80 and over; Male; 0303 health sciences; Adolescent; Gene Expression Profiling; High-Throughput Nucleotide Sequencing; Genomics; Middle Aged; Article; Kidney Neoplasms; Cohort Studies; Gene Expression Regulation, Neoplastic; Young Adult; 03 medical and health sciences; Humans; Female; Neoplasm Metastasis; Child; Carcinoma, Renal Cell; Aged

The genomic landscape of primary clear cell renal cell carcinoma (ccRCC) has been well described. However, little is known about cohort genomic alterations (GA) landscape in ccRCC metastases, or how it compares to primary tumours in aggregate. The genomic landscape of metastases may have biological, clinical, and therapeutic implications.We collected targeted next-generation sequencing mutation calls from two independent cohorts and described the metastases GA landscape and descriptively compared it to the GA landscape in primary tumours.The cohort 1 (n = 578) consisted of 349 primary tumours and 229 metastases. Overall, the most common mutations in the metastases were VHL (66.8%), PBRM1 (41.87%), and SETD2 (24.7%). TP53 was more frequently mutated in metastases compared to primary tumours (14.85% versus 8.9%; p = 0.031). No other gene had significant difference in the cohort frequency of mutations between the metastases and primary tumours. Mutation burden was not significantly different between the metastases and primary tumours or between metastatic sites. The second cohort (n = 257) consisted of 177 primary tumours and 80 metastases. No differences in frequency of mutations or mutational burden were observed between primaries and metastases.These data support the theory that ccRCC primary tumours and metastases encompass a uniform distribution of common genomic alterations tested by next-generation sequencing targeted panels. This study does not address variability between matched primary tumours and metastases or the change in genomic alterations over time and after sequential systemic therapies.