Association between copy-number alteration of +20q, -14q and -18p and cross-sensitivity to tyrosine kinase inhibitors in clear-cell renal cell carcinoma.

ABSTRACT:

Background

We aim to explore association between copy number alteration (CNA) and sensitivity to common tyrosine kinase inhibitors (TKIs) used in clear-cell renal cell carcinoma (ccRCC) treatment.

Methods

CNA with related sensitivity profiles were extracted from the Genomics of Drug Sensitivity in Cancer (GDSC) dataset and was cross-referenced with common CNA in ccRCC in the Cancer Genome Atlas (TCGA) dataset. Functional annotation was profiled using GSEA and NET-GE. Target genes within cytobands of interest were screened in silico and validated in vitro using proliferation assays in A498 and 786-O ccRCC cells.

Results

Four TKIs (Sunitinib, Cabozantinib, Axitinib and Sorafenib) that were clinically used in ccRCC were selected. In silico analysis showed gain of 20q (+2

SUBMITTER: Wang L 

PROVIDER: S-EPMC7541266 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature