Redefining synchronous colorectal cancer on the basis of clonality

Background: Synchronous colorectal cancer (SCRC) is not widely studied, and one of its most striking aspects the possible clonal origin of at least a part of the cases. Materials and methods: We studied 104 paired-SCRCs of 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; the results were confirmed by next generation sequencing of the main CRC-related genes. We categorized the ensuing groups according to colon location, trying to find differential phenotypes with clinical implications. Results: The SCRC Monoclonal group (M) (19 cases) was divided into Monosegmental (MM) and Pancolonic (MP) groups. The MM subgroup consisted of 10 cases (19% of the total), while the MP group contained 9 cases (17%). The SCRC Polyclonal group (P) (33 cases) was also divided into Monosegmental (PM) and Pancolonic (PP) groups: 19 cases were PM (37%), showing preference for location in the left colon (17 cases, 89%), whereas 14 cases were PP (27%). Correlations with clinical features were mainly related to prognosis and familial cancer history. The MM group showed a high rate of mucinous tumors (37.5%), had the lowest mean number of tumors and associated polyps, and the worst prognosis. The MP group included the youngest age at diagnosis and the largest mean-number of associated polyps, had comparatively intermediate mean number of tumors, and showed the best prognosis and a familial cancer component. The PM group seemed to be a “frontier” group. Finally, the PP group also exhibited a mucin component, with the highest mean-number of tumors (4.6) compared with the mean-number of polyps (7.7), had a poor prognosis and consisted of sporadic cases. Conclusions: The statistical application we employed seems to define clonality more accurately in SCRC, and this, together with the tumor locations, helped us to configure a classification with prognostic and clinical value. These categories may serve as a starting point to analyze more selectively the molecular basis of SCRC and its relationship with environmental factors. A total of 53 individuals diagnosed with Synchronous colorectal cancer (SCRC) were consecutively collected from January 2006 at the 12 de Octubre University Hospital (Madrid). We defined a CRC as SCRC when 2 or more histologically distinct colorectal tumors were identified in the same patient at the same time or in a period less than six month after the first diagnosis.