Abstract
BackgroundAllelic imbalance (AI) in tumors is caused by chromosomal and sub-chromosomal gains and losses.ResultsWe evaluated AI at 109,086 germline exonic SNP loci in four cancer types, and identified a set of SNPs that demonstrate strong tumor allele specificity in AI events. Further analyses demonstrated that these alleles show consistently different frequencies in the cancer population compared to the healthy population and are significantly enriched for predicted protein-damaging variants. Moreover, genes harboring SNPs that demonstrate allele specificity are enriched for cancer-related biological processes and are more likely to be essential in cancer cells.ConclusionsIn summary, our study provides a unique and complementary method to identify genes and variants that are relevant to carcinogenesis.
Highlights
Allelic imbalance (AI) in tumors is caused by chromosomal and sub-chromosomal gains and losses
All the sequence data and clinical information are available from the Cancer Genome Atlas database the GDC data portal [8]
We retrieved the protein–protein interaction networks (PPI) for the genes affected by somatic selection in the four cancer types, based on which we identified 3 modules with significantly higher burdens of somatic selection (Fig. 4a–c and Additional file 10: Table S7)
Summary
Allelic imbalance (AI) in tumors is caused by chromosomal and sub-chromosomal gains and losses. Somatic DNA alterations are crucial for the acquisition of tumor-related traits. Allelic imbalance (AI), occurs when a segment of one parental chromosome increases or decreases in copy number relative to the other. If the parental homolog with the resulting larger copy number—referred to as the “promoted” homolog—carries a genetic variant that is more advantageous to tumor growth than that carried by the other homolog, cells promoting the advantageous allele gain a selective advantage. The resulting tumor can be observed to harbor more copies of this allele than its counterpart. AI can be viewed as a readout for allelic selection, thereby nominating candidate genes and alleles of importance (Fig. 1a).
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