Local recurrences at the anastomotic area are clonally related to the primary tumor in sporadic colorectal carcinoma

PURPOSE: Anastomotic recurrences (AR) occur in 2–10% of colorectal carcinoma cases after resection of primary tumor (PT). Currently, there are no molecular data investigating their genetic profile and multiple theories exist about their pathogenesis. The aim of our study was to compare the genomic profile of AR to that of the patients’ corresponding matched PT and, when available, to a distant metastasis (DM). EXPERIMENTAL DESIGN: Thirty-six tumors from 14 patients were genotyped using a capture-based, next-generation assay to define the mutational status of 341 cancer-associated genes. All patients had R0 resection of their PT and AR occurred 1.1−7.0 years following PT resection. A DM or a second AR was analyzed in 8 patients. All tumors were microsatellite stable except in one patient with Lynch syndrome. RESULTS: A total of 254 somatic mutations were detected including 138 mutations in the microsatellite stable (MSS) cases. The most commonly mutated genes were APC, KRAS, TP53, PIK3CA, ATM and PIK3R1. In all patients with MSS tumors the AR and PT shared between 50−100% of mutations, including mutations in key driver genes, consistent with these tumors being clonally related. Genetic events private to DM were not detected in AR and phylogenetic analysis showed that ARs were more closely related to PT than DM. In the Lynch syndrome patient the PT and AR showed distinct somatic mutations consistent with independent primaries. CONCLUSIONS: ARs are clonally related to PT in sporadic colorectal carcinomas and do not appear to represent seeding of the anastomotic site by distant metastases.