Similarities of Molecular Genetic Changes in Synchronous and Metachronous Colorectal Cancers Are Limited and Related to the Cancers’ Proximities to Each Other

Abstract

Synchronous and metachronous colorectal cancers are distinct primary neoplasms diagnosed either simultaneously or sequentially in the same patient. Because they arise in a common genetic and environmental background, they offer a unique opportunity to study molecular genetic changes occurring during carcinogenesis. We evaluated tumors from 50 patients with synchronous and five additional patients with metachronous cancers for loss of heterozygosity of the genes APC and DCC, KRAS and BRAF gene mutations, and microsatellite instability and methylation. Standard PCR methods were used. Approximately two thirds of the synchronous tumors that were informative for each of the five primary molecular genetic changes showed the same results when located in the same colon segment. However, there was less consistency of molecular findings for the synchronous pairs separated by one or more colonic segments, with half or more of these pairs showing different molecular results. Metachronous tumors also showed variation of molecular genetic findings, but this was less when the subsequent tumor was close to the segment of the first tumor. Molecular genetic findings between synchronous and metachronous tumors can be different, even for tumors sharing the same microenvironment of the same colon segment. These findings support the concept that a mutagen might produce different genetic pathways in two proximate tumors.