Mutant-Allele Tumor Heterogeneity (MATH) Scores Correlate with Risk of Metastases in Colon Cancer

Abstract Background Colorectal cancer is a leading cause of cancer related mortality, has a very broad mutational spectrum, and there is no clinically available biomarker that can predict which patients with stage II or stage III colorectal cancer will develop metastatic disease. Patients and Methods We used a targeted next-generation sequencing approach to analyze the mutational spectra in stage II and III colon cancer patient samples. Results Amidst a broad range of acquired mutations and variants, we found evidence of tumor heterogeneity that distinguished the tumors in different groups. When heterogeneity was quantified using the Mutant-Allele Tumor Heterogeneity (MATH) score, there was a strong correlation between higher MATH score and risk of metastases. Conclusions Measures of tumor heterogeneity may be useful biomarkers for identifying patients with colon cancer that are at risk of developing metastases. This may allow for more specific, tailored follow-up and adjuvant therapies after standard surgery.