Graduate School of Biomedical Sciences; Program in Bioinformatics and Integrative Biology
Amino Acids, Peptides, and Proteins | Bioinformatics | Cancer Biology | Computational Biology | Genetic Phenomena | Genetics | Molecular Genetics | Neoplasms | Nucleic Acids, Nucleotides, and Nucleosides
Imbalanced expression of somatic alleles in cancer can suggest functional and selective features, and can therefore indicate possible driving potential of the underlying genetic variants. To explore the correlation between allele frequency of somatic variants and total gene expression of their harboring gene, we used the unique data set of matched tumor and normal RNA and DNA sequencing data of 5523 distinct single nucleotide variants in 381 individuals across 10 cancer types obtained from The Cancer Genome Atlas (TCGA). We analyzed the allele frequency in the context of the variant and gene functional features and linked it with changes in the total gene expression. We documented higher allele frequency of somatic variants in cancer-implicated genes (Cancer Gene Census, CGC). Furthermore, somatic alleles bearing premature terminating variants (PTVs), when positioned in CGC genes, appeared to be less frequently degraded via nonsense-mediated mRNA decay, indicating possible favoring of truncated proteins by the tumor transcriptome. Among the genes with multiple PTVs with high allele frequency, ARID1, TP53 and NSD1 were known key cancer genes. All together, our analyses suggest that high allele frequency of tumor somatic variants can indicate driving functionality and can serve to identify potential cancer-implicated genes.
Rights and Permissions
© The Author(s) 2018. Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
DOI of Published Version
Sci Rep. 2018 May 16;8(1):7735. doi: 10.1038/s41598-018-25462-0. Link to article on publisher's site
Spurr, Liam; Li, Muzi; Alomran, Nawaf; Zhang, Qianqian; Restrepo, Paula; Movassagh, Mercedeh; Trenkov, Chris; Tunnessen, Nerissa; Apanasovich, Tatiyana; Crandall, Keith A.; Edwards, Nathan; and Horvath, Anelia, "Systematic pan-cancer analysis of somatic allele frequency" (2018). Open Access Articles. 3477.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Amino Acids, Peptides, and Proteins Commons, Bioinformatics Commons, Cancer Biology Commons, Computational Biology Commons, Genetic Phenomena Commons, Genetics Commons, Molecular Genetics Commons, Neoplasms Commons, Nucleic Acids, Nucleotides, and Nucleosides Commons