Cancer-associated mutations in normal colorectal mucosa adjacent to sporadic neoplasia

Introduction Colorectal cancer (CRC) arises in a multistep process of carcinogenesis from normal mucosa. The earliest precursor might be a morphologically inconspicuous precancerous field harboring cancer-associated mutations.

Aim To determine cancer-associated mutations in normal mucosa adjacent to colorectal neoplasia and to compare the spectrum of genetic alterations with the matched neoplastic tissue.

Methods We systematically analyzed genetic alterations in 77 tissue samples from 30 patients with sporadic colorectal neoplasms (large adenomas or adenocarcinoma) and matched adjacent normal mucosa, as well as normal rectal tissue. We profiled mutations associated with CRC by targeted sequencing of 46 genetic loci using 157 custom amplicons and a median depth of 42,655 reads per loci.

Results Multiple mutations were found in colorectal neoplasms, most frequently in APC, KRAS and TP53. In a subgroup of 11 of 30 patients, alterations were also detected in non-neoplastic mucosa. These mutations were divergent from those in matched neoplasms. The total alteration count and the mutant allele frequency were lower in adjacent tissue compared to neoplasms. We found that younger patients (≤70 years) are less likely affected by mutations in non-neoplastic mucosa than older patients (>70 years, p = 0.013), while no association was observed for other variables, including type, location and differentiation of neoplasia, as well as previous history of polyps.

Conclusion Our data shows that cancer-associated mutations can be found in non-neoplastic tissue of a subgroup of patients with colorectal neoplasms. Further studies are needed to specify the risk of occurrence and recurrence of neoplasia in this patient population.

Publication History

Article published online:
08 September 2020