The genomic landscape of metastatic clear cell renal cell carcinoma after systemic therapy.

TitleThe genomic landscape of metastatic clear cell renal cell carcinoma after systemic therapy.
Publication TypeJournal Article
Year of Publication2022
Authorsvan der Mijn JC, Eng KW, Chandra P, Fernandez E, Ramazanoglu S, Sigaras A, Oromendia C, Gudas LJ, Tagawa ST, Nanus DM, Faltas BF, Beltran H, Sternberg CN, Elemento O, Sboner A, Mosquera JMiguel, Molina AM
JournalMol Oncol
Date Published2022 Jun
KeywordsCarcinoma, Renal Cell, DNA Copy Number Variations, F-Box-WD Repeat-Containing Protein 7, Genomics, Humans, Kidney Neoplasms, Mutation, Nuclear Proteins, RNA-Binding Proteins

Primary clear cell renal cell carcinoma (ccRCC) has been previously characterized, but the genomic landscape of metastatic ccRCC is largely unexplored. Here, we performed whole exome sequencing (WES) in 68 samples from 44 patients with ccRCC, including 52 samples from a metastatic site. SETD2, PBRM1, APC and VHL were the most frequently mutated genes in the metastatic ccRCC cohort. RBM10 and FBXW7 were also among the 10 most frequently mutated genes in metastatic tissues. Recurrent somatic copy number variations (CNV) were observed at the previously identified regions 3p25, 9p21 and 14q25, but also at 6p21 (CDKN1A) and 13q14 (RB1). No statistically significant differences were found between samples from therapy-naïve and pretreated patients. Clonal evolution analyses with multiple samples from 13 patients suggested that early appearance of CNVs at 3p25, 9p21 and 14q25 may be associated with rapid clinical progression. Overall, the genomic landscapes of primary and metastatic ccRCC seem to share frequent CNVs at 3p25, 9p21 and 14q25. Future work will clarify the implication of RBM10 and FBXW7 mutations and 6p21 and 13q14 CNVs in metastatic ccRCC.

Alternate JournalMol Oncol
PubMed ID35231161
PubMed Central IDPMC9208073
Grant ListR01 DK113088 / DK / NIDDK NIH HHS / United States
Related Faculty: 
Juan Miguel Mosquera, M.D. Andrea Sboner, Ph.D.

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