Genomic Profiling of Cancerous Areas, Dysplasia, and Background Mucosa in Ulcerative Colitis-associated Colorectal Cancer

Background/Aim: Ulcerative colitis (UC) is associated with an increased risk of colorectal cancer (CRC), and unlike sporadic CRC, colitis-associated CRC (CAC) develops through a dysplasia–carcinoma sequence rather than the traditional adenoma–carcinoma pathway. However, studies that have simultaneously analyzed background mucosa, dysplasia, and carcinoma within the same patient remain limited. This study aimed to identify characteristic genetic abnormalities in UC-associated CRC by analyzing background mucosa, dysplasia, and carcinoma using a targeted gene panel.

Patients and Methods: Herein, 12 cases of CAC were examined. Formalin-fixed paraffin-embedded samples from eight background mucosae, 12 dysplastic lesions, and 15 carcinoma lesions, together with matched blood samples as normal controls, were subjected to targeted gene panel analysis using the Todai OncoPanel.

Results: TP53 mutations were identified in two of the 12 dysplastic lesions (16.7%) and 12 of the 15 carcinoma lesions (80.0%). APC and KRAS, which are frequently mutated in sporadic CRC, were detected in one and two patients, respectively. Among the 12 cases analyzed, dysplasia and carcinoma from the same patient were available for comparison in 11 cases; of these, only one case harbored the pathogenic variants KRAS G12S and CHEK2 K373E, as well as the BRCA2 A1652S variant of uncertain significance.

Conclusion: CAC exhibits distinct mutational characteristics compared with sporadic CRC and different genetic abnormalities in each lesion may contribute to the dysplasia–carcinoma sequence.