Do the MATH

Genomics Tool Could Help Predict Tumor Aggressiveness, Treatment Outcomes

Edward MrozJames RoccoA new method for measuring genetic variability within a tumor could help doctors identify patients with aggressive cancers that are more likely to resist therapy, according to a study led by researchers now at The Ohio State University Comprehensive Cancer Center – James Cancer Hospital and Solove Research Institute (OSUCCC – James).

Researchers used a scoring method they developed called MATH (mutant-allele tumor heterogeneity) to measure the genetic variability among cancer cells within tumors from 305 patients with head and neck cancer. High MATH scores corresponded to tumors with many differences among the gene mutations present in different cancer cells.

Cancers that showed high genetic variability—called “intratumor heterogeneity”—correlated with lower patient survival. If prospective studies verify the findings, MATH scores could help identify the most effective treatments and predict prognosis.

Researchers have long hypothesized that multiple subpopulations of mutated cells within a single cancer lead to worse clinical outcomes; however, oncologists do not use tumor heterogeneity to guide clinical care decisions or assess disease prognosis because there is no easy-to-implement method of doing so in clinical practice.

To address this need, James Rocco, MD, PhD, and colleagues developed MATH to help doctors measure genetic variability in tumors and to help guide treatment decisions. Findings from this study confirm that high genetic variability within a patient’s tumor is related to increased mortality in head and neck squamous cell carcinoma. 

“Genetic variability within tumors is likely why people fail treatment,” says Rocco, professor and director of the Division of Head and Neck Oncology at Ohio State. “In patients with high heterogeneity tumors, it is likely that there are several clusters of underlying mutations—in the same tumor—driving the cancer. So their tumors are likely to have some cells that are already resistant to therapy.”

Rocco was corresponding author on the study. Edmund Mroz, PhD, research associate professor in the Department of Otolaryngology – Head and Neck Surgery at Ohio State, was first author.

Published in the journal PLOS Medicine.

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