Login to Access Video or Poster Abstract: MP39-03
Sources of Funding: This study was supported in part by the Sidney Kimmel Center for Prostate and Urologic Cancers and by the National Cancer Institute T32 CA082088 (MG, BM)._x000D_ NIH Ruth L. Kirschstein National Research Service Award T32CA082088 _x000D_ German Research Foundation (DFG) Grant CA1403/1-1

Introduction

Discovery and understanding of the molecular drivers of clear cell renal cell carcinoma (ccRCC) has led to the development of targeted therapies. Despite advances in these agents, metastatic disease remains largely incurable. Exploration of the biology of metastatic tumors may provide insights into patterns and routes of metastases that could lead to the identification of differences in therapeutic vulnerabilities. We aim to evaluate somatic mutations (SM) associated with organ tropism in a cohort of metastatic ccRCC patients.

Methods

We identified all patients with ccRCC who had a metastatic tumor sequenced at our institution from 2001 to 2016 using Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT), a next-generation sequencing assay studying a custom panel of 410 (previously 341) targetable genes commonly mutated in cancer. Fishers exact test was used to evaluate associations between recurrent SM and sites of metastasis.

Results

A total of 94 samples from 93 patients were analyzed. Metastatic tissue was obtained from the following sites: 26 (28%) lung, 20 (21%) bone, 13 (14%) lymph node, 7 (7%) adrenal gland, 7 brain (7%), and 21 other sites (22%). The most common alterations were VHL (85%), PBRM1 (45%), SETD2 (37%), BAP1 (20%). When analyzing samples by site, metastases to pleura presented with enrichment in BAP1 mutations (P=0.008), adrenal gland metastases had an enrichment in MED12 mutations (P=0.005), and NF2 alterations were found to be associated with bone metastases (P=0.08). _x000D_ _x000D_

Conclusions

Our data suggest SM may be correlated with a site-specific pattern of metastatic spread. In our cohort, the presence of BAP1, MED12 and NF2 mutations was associated with increased pleural, adrenal gland, and bone metastasis, respectively. The extent to which the identified molecular factors contribute to the development of these characteristics needs to be analyzed in further studies. Patterns of SM in ccRCC metastasis could result in the creation of gene signatures predicting metastasis.

Funding

This study was supported in part by the Sidney Kimmel Center for Prostate and Urologic Cancers and by the National Cancer Institute T32 CA082088 (MG, BM)._x000D_ NIH Ruth L. Kirschstein National Research Service Award T32CA082088 _x000D_ German Research Foundation (DFG) Grant CA1403/1-1