Overexpressed somatic alleles are enriched in functional elements in Breast Cancer

Area of Science:

• Genomics
• Cancer Biology
• Transcriptomics

Background:

• Asymmetric allele content in the transcriptome can indicate functional and selective genetic features.
• Imbalanced alleles in diploid genome regions are under-explored in cancer research.

Purpose of the Study:

• To systematically quantify and integrate variant allele fraction from RNA and DNA sequence data in breast cancer patients.
• To test the correlation between allele prevalence and functionality in known cancer-implicated genes.
• To explore allele-specific expression patterns in the cancer transcriptome.

Main Methods:

• Utilized The Cancer Genome Atlas (TCGA) RNA and DNA sequencing data from breast cancer patients.
• Quantified variant allele fraction (VAF) from both RNA and DNA data.
• Correlated allele prevalence with gene functionality using the Cancer Gene Census (CGC).

Main Results:

• Documented significant allele-preferential expression of functional variants in CGC genes and across the entire dataset.
• Observed frequent allele-specific overexpression of variants in tumor-suppressor genes.
• Identified over-expressed variants in non-CGC genes.

Conclusions:

• Somatic allele expression provides integrated features of the cancer transcriptome.
• Asymmetric alleles contain significant information for understanding cancer biology.
• Allele-specific expression patterns, particularly in tumor-suppressor genes, are crucial for cancer research.