Interrogating Mutant Allele Expression via Customized Reference Genomes to Define Influential Cancer Mutations

Adam D. Grant, Paris Vail, Megha Padi, Agnieszka Witkiewicz, Erik S. Knudsen

Research output: Contribution to journalArticle

Abstract

Genetic alterations are essential for cancer initiation and progression. However, differentiating mutations that drive the tumor phenotype from mutations that do not affect tumor fitness remains a fundamental challenge in cancer biology. To better understand the impact of a given mutation within cancer, RNA-sequencing data was used to categorize mutations based on their allelic expression. For this purpose, we developed the MAXX (Mutation Allelic Expression Extractor) software, which is highly effective at delineating the allelic expression of both single nucleotide variants and small insertions and deletions. Results from MAXX demonstrated that mutations can be separated into three groups based on their expression of the mutant allele, lack of expression from both alleles, or expression of only the wild-type allele. By taking into consideration the allelic expression patterns of genes that are mutated in PDAC, it was possible to increase the sensitivity of widely used driver mutation detection methods, as well as identify subtypes that have prognostic significance and are associated with sensitivity to select classes of therapeutic agents in cell culture. Thus, differentiating mutations based on their mutant allele expression via MAXX represents a means to parse somatic variants in tumor genomes, helping to elucidate a gene’s respective role in cancer.

Original languageEnglish (US)
Article number12766
JournalScientific Reports
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2019

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Alleles
Genome
Mutation
Neoplasms
vif Genes
RNA Sequence Analysis
Software
Nucleotides
Cell Culture Techniques
Phenotype
Gene Expression

ASJC Scopus subject areas

  • General

Cite this

Interrogating Mutant Allele Expression via Customized Reference Genomes to Define Influential Cancer Mutations. / Grant, Adam D.; Vail, Paris; Padi, Megha; Witkiewicz, Agnieszka; Knudsen, Erik S.

In: Scientific Reports, Vol. 9, No. 1, 12766, 01.12.2019.

Research output: Contribution to journalArticle

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