Exome Sequencing of Paired Colorectal Carcinomas and Synchronous Liver Metastases for Prognosis and Therapy Prediction
Abstract
This study used whole exome sequencing to analyze somatic variant spectra in retrospectively collected pairs of primary tumors and synchronous liver metastases from surgically treated patients with colorectal carcinomas. Mutational profiles served for comparing groups of patients stratified by response to chemotherapy and survival.
The study utilized sample pairs from 20 patients diagnosed and treated at a single center. The most frequently altered oncodrivers were APC (55% in primaries and 60% in metastases), TP53 (50/45), TRIP11 (30/5), FAT4 (20/25), and KRAS (15/25).
A high load of variants with high predicted effect (i.e., mainly frameshift, splice site, and nonsense) was associated with prolonged relapse-free survival while the opposite was observed for variants with moderate effect (i.e., mostly missense). Variants in individual genes, e.g., ATM, KRAS, and MUC5AC or oncodriver pathways represented poor prognostic factors with significant differences between primary tumor and metastasis.
No gene or profile was significantly associated with the response to chemotherapy. Taken together, we report subtle differences in exome mutational profiles between paired primary tumors and synchronous liver metastases except for TRIP11 and several putative prognostic genes and profiles.
After functional characterization, our data may provide a lead for studies focused on utilizing these findings in precision oncology.