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

Overview of attention for article published in BMC Genomics, August 2016
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Title
An integrative genomics approach for identifying novel functional consequences of PBRM1 truncated mutations in clear cell renal cell carcinoma (ccRCC)
Published in
BMC Genomics, August 2016
DOI 10.1186/s12864-016-2906-9
Pubmed ID
Authors

Yuanyuan Wang, Xingyi Guo, Michael J. Bray, Zhiyong Ding, Zhongming Zhao

Abstract

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. 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. We identified 613 differentially expressed genes (128 up-regulated and 485 down-regulated genes using cutoff |log2FC| < 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, |log2FC| < 1, p < 0.01) and 185 significantly altered microRNAs (|log2FC| < 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. 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.

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Mendeley readers

The data shown below were compiled from readership statistics for 23 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 23 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 10 43%
Other 4 17%
Student > Bachelor 4 17%
Professor > Associate Professor 2 9%
Researcher 1 4%
Other 1 4%
Unknown 1 4%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 7 30%
Medicine and Dentistry 5 22%
Agricultural and Biological Sciences 2 9%
Computer Science 2 9%
Engineering 2 9%
Other 3 13%
Unknown 2 9%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 26 August 2016.
All research outputs
#6,284,144
of 8,282,830 outputs
Outputs from BMC Genomics
#4,595
of 5,854 outputs
Outputs of similar age
#180,303
of 253,715 outputs
Outputs of similar age from BMC Genomics
#208
of 273 outputs
Altmetric has tracked 8,282,830 research outputs across all sources so far. This one is in the 13th percentile – i.e., 13% of other outputs scored the same or lower than it.
So far Altmetric has tracked 5,854 research outputs from this source. They receive a mean Attention Score of 4.2. This one is in the 11th percentile – i.e., 11% of its peers scored the same or lower than it.
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We're also able to compare this research output to 273 others from the same source and published within six weeks on either side of this one. This one is in the 12th percentile – i.e., 12% of its contemporaries scored the same or lower than it.