期刊
CLINICAL COLORECTAL CANCER
卷 18, 期 2, 页码 102-109出版社
CIG MEDIA GROUP, LP
DOI: 10.1016/j.clcc.2019.02.003
关键词
Bioinformatics; Colorectal cancer; Personalized medicine; Targeted sequencing; Translational research
类别
资金
- National Institutes of Health [5R01CA170250, 5R01DE023222, 5P30CA118100]
- State of New Mexico
- UNM Comprehensive Cancer Center [P30CA118100]
A standard therapy for locally advanced cancers includes neoadjuvant chemoradiation; however, currently there is no way of knowing which patients have disease that will respond to such therapy. We analyzed 21 pretreatment rectal cancer biopsy samples and found a positive correlation of the response to therapy with a quantitative mutant-allele tumor heterogeneity (MATH) score. This next-generation sequencing derived score may serve as a biomarker for response to therapy. Background: Neoadjuvant chemoradiotherapy (nCRT) is the standard of care for locally advanced adenocarcinoma of the rectum, but it is currently unknown which patients have disease that will respond. This study tested the correlation between response to nCRT and intratumoral heterogeneity using next-generation sequencing assays. Patients and Methods: DNA was extracted from formalin-fixed, paraffin-embedded biopsy samples from a cohort of patients with locally advanced rectal adenocarcinoma (T3/4 or N1/2 disease) who received nCRT. High read-depth sequencing of > 400 cancer-relevant genes was performed. Tumor mutations and variant allele frequencies were used to calculate mutant-allele tumor heterogeneity (MATH) scores as measures of intratumoral heterogeneity. Response to nCRT was pathologically scored after surgical resection. Results: Biopsy samples from 21 patient tumors were analyzed. Eight patients had disease noted to have complete response, 2 moderate, 4 minimal, and 7 poor. Higher MATH scores correlated with poorer response to treatment, demonstrating significantly increased tumor heterogeneity compared to complete response (P = .039). Conclusion: The application of MATH scores as a measure of tumor heterogeneity may provide a useful biomarker for treatment response in locally advanced rectal cancer. (C) 2019 The Authors. Published by Elsevier Inc.
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