Mutant Allele Tumor Heterogeneity (MATH) and Head and Neck Squamous Cell Carcinoma

Abstract

Intra-tumor heterogeneity, variation between individual tumor cells within a patient’s tumor, is increasingly seen as a critical mechanism underlying treatment resistance and therapeutic failure. Despite this growing awareness, few methods to assess intra-tumor heterogeneity exist outside the research laboratory, especially in the absence of a known marker. Mutant allele tumor heterogeneity (MATH) is a novel, non-biased, quantitative method to assess genetic heterogeneity based on tumor next generation exome sequencing. The quantitative aspect of MATH has allowed it to be verified as an actionable biomarker in a retrospective HNSCC data set with available exome sequencing and clinical data. In addition, it was also capable of stratifying patient outcome after controlling for other high-risk features such as p53 mutation, HPV status, and advanced tumor stage. Future work will explore the predictive power of MATH in larger data sets such as The Cancer Genome Atlas and examine the underlying cellular mechanisms responsible for intra-tumor heterogeneity.