Mutant-Allele Tumor Heterogeneity Scores Correlate With Risk of Metastases in Colon Cancer

There is no clinical biomarker that predicts which patients with stage II or III colon cancers are at risk for developing metastases. A bioinformatics approach using the Mutant-Allele Tumor Heterogeneity score for tumor heterogeneity might identify this high-risk subset of patients to tailor adjuvant therapies and surveillance. 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 might be useful biomarkers for identifying patients with colon cancer who are at risk of developing metastases. This might allow for more specific, tailored follow-up and adjuvant therapies after standard surgery.