Intratumor Heterogeneity of MYO18A and FBXW7 Variants Impact the Clinical Outcome of Stage III Colorectal Cancer.

ABSTRACT: Many studies failed to demonstrate benefit from the addition of targeted agents to current standard adjuvant FOLFOX chemotherapy in stage III colorectal cancer (CRC) patients. Intratumor heterogeneity may foster the resistant subclones and leads to cancer recurrence. Here, we built a cancer evolution model and applied machine learning analysis to identify potential therapeutic targets. Among 78 CRC cases, whole-genome (WGS) and deep targeted sequencing data generated from paired blood and primary tumor were used for phylogenetic tree reconstruction. Genetic alterations in the PI3K/AKT, and RTK oncogenic signaling pathways were commonly detected in founding clones. The dominant subclones frequently exhibited dysregulations in the TP53, FBXW7/NOTCH1 tumor suppression, and DNA repair pathways

SUBMITTER: Lin PC 

PROVIDER: S-EPMC7658598 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature