Redefining synchronous colorectal cancers based on tumor clonality.

ABSTRACT

To analyze the possible clonal origin of a part of Synchronous colorectal cancer (SCRC), we studied 104 paired-SCRCs from 52 consecutive patients without hereditary forms of CRC. We used a Single-Nucleotide Polymorphism array to characterize the genomic profiles, and subsequently used a statistical application to define them according to clonality within the same individual. We categorized the ensuing groups according to colonic location to identify differential phenotypes. The SCRC Monoclonal group (M) (19 cases) was divided into Monosegmental (MM) and Pancolonic (MP) groups. The SCRC Polyclonal group (P) (33 cases) was also divided into Monosegmental (PM) and Pancolonic (PP), the first exhibiting preference for left colon. The MM group showed a high rate of mucinous tumors, the lowest mean-number of tumors and associated-polyps, and the worst prognosis. The MP group included the largest mean-number of associated-polyps, best prognosis and familial cancer component. The PM group seemed to be a "frontier" group. Finally, the PP group also exhibited a mucin component, the highest mean-number of tumors (4.6) compared with the mean-number of polyps (7.7), poor prognosis and sporadic cases. Most relevant differential genomic regions within M groups were gains on 1q24 and 8q24, and deletions on 1p21 and 1p23 for MM, while within P were the gains on 7q36 and deletions on 1p36 for PM. The statistical application employed seems to define clonality more accurately in SCRC -more likely to be polyclonal in origin-, and together with the tumor locations, helped us to configure a classification with prognostic and clinical value.