Systematic pan-cancer analysis of somatic allele frequency

Scientific Reports
Liam SpurrAnelia Horvath

Abstract

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...Continue Reading

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Citations

Nov 2, 2019·Genes·Enrique Hernández-LemusSoledad Ochoa
Aug 8, 2020·Journal of Bioinformatics and Computational Biology·Shanchen PangXinzeng Wang
Nov 3, 2020·The Journal of Pathology·Robin Jn CoopeMarco A Marra
Aug 10, 2019·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Halei C BenefieldMelissa A Troester
Apr 15, 2020·Cancer Cell·Yonina R Murciano-GoroffAlison M Schram
Apr 20, 2021·Frontiers in Oncology·Alex FriedlaenderAlfredo Addeo

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Software Mentioned

Cufflinks
ESTIMATE
TRANSFAC
Combined Annotation Dependent Depletion ( CADD )
Genomic Evolutionary Rate Profiling ( GERP ) Analysis Hidden M...
Integrative Genomics Viewer
Integrative Genome Viewer , IGV
CADD
TCGA
Tuxedo suite

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