Analysis of clonal evolution in colorectal cancer.

3510 Background: Comparisons of primary tumor and metastases (met) from the same individual patients (pts) highlight intratumor heterogeneity and clonal evolution with treatment. Results of genomic mutation analysis may guide treatment decisions in colorectal cancer (CRC). Methods: Ultra-deep (mean 35,000x coverage) amplicon sequencing was performed for hotspot regions of TP53, APC, KRAS, NRAS, PIK3CA, and BRAF on 36 DNA samples isolated from metachronous FFPE tumor specimens from 15 pts with CRC. The cohort included 10 pts with tissue from the primary and ≥1 met, four pts with pairs of mets, and one pt with a recurrent tumor at the primary site. One sample from each pt had prior analysis with a customized 23-gene panel for Sequenom. Samples were compared for presence of mutation and variant allele frequency (all-freq). Results: All KRAS, NRAS, PIK3CA, and BRAF mutations identified using Sequenom were confirmed by ultra-deep sequencing. Analysis for the six pts with KRAS codon 12 mutation, three pts with ...