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Background  Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer. Recent large-scale next-generation sequencing analyses reveal that  PBRM1  is the second most frequently mutated gene harboring many truncated mutations and has a suspected tumor suppressor role in ccRCC. However, the biological consequences of  PBRM1  somatic mutations (e.g., truncated mutations) that drive tumor progression in ccRCC remain unclear.    Methods  In this study, we proposed an integrative genomics approach to explore the functional consequences of  PBRM1  truncated mutations in ccRCC by incorporating somatic mutations, mRNA expression, DNA methylation, and microRNA (miRNA) expression profiles from The Cancer Genome Atlas (TCGA). We performed a systematic analysis to detect the differential molecular features in a total of 11 ccRCC samples harboring  PBRM1  truncated mutations from the 33 “pan-negative” ccRCC samples. We excluded the samples that had any of the five high-confidence driver genes ( VHL ,  BAP1 ,  SETD2, PTEN  and  KDM5C ) reported in ccRCC to avoid their possible influence in our results.    Results  We identified 613 differentially expressed genes (128 up-regulated and 485 down-regulated genes using cutoff |log 2 FC| < 1 and  p  < 0.05) in  PBRM1  mutated group versus “pan-negative” group. The gene function enrichment analysis revealed that down-regulated genes were significantly enriched in extracellular matrix organization (adjusted  p  = 2.05 × 10 −7 ), cell adhesion (adjusted  p  = 2.85 × 10 −7 ), and ion transport (adjusted  p  = 9.97 × 10 −6 ). Surprisingly, 26 transcriptional factors (TFs) genes including  HOXB9, PAX6  and  FOXC1  were found to be significantly differentially expressed (23 over expressed TFs and three lower expressed TFs) in  PBRM1  mutated group compared with “pan-negative” group. In addition, we identified 1405 differentially methylated CpG sites (targeting 1308 genes, |log 2 FC| < 1,  p  < 0.01) and 185 significantly altered microRNAs (|log 2 FC| < 1,  p  < 0.05) associated with truncated  PBRM1  mutations. Our integrative analysis suggested that methylation and miRNA alterations were likely the downstream events associated with  PBRM1  truncation mutations.    Conclusions  In summary, this study provided some important insights into the understanding of tumorigenesis driven by  PBRM1  truncated mutations in ccRCC. The approach may be applied to many driver genes in various cancers.    Electronic supplementary material  The online version of this article (doi:10.1186/s12864-016-2906-9) contains supplementary material, which is available to authorized users.

An integrative genomics approach for identifying novel functional consequences of PBRM1 truncated mutations in clear cell renal cell carcinoma (ccRCC)