Ann Coloproctol.  2022 Feb;38(1):72-81. 10.3393/ac.2021.00290.0041.

Molecular characterization of dysplasia-initiated colorectal cancer with assessing matched tumor and dysplasia samples

Affiliations
  • 1Department of Genome Medicine and Science, Gachon University College of Medicine, Incheon, Korea
  • 2Gachon Institute of Genome Medicine and Science, Gachon University Gil Medical Center, Incheon, Korea
  • 3Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
  • 4Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University, Seoul, Korea
  • 5Department of Surgery, Kyung Hee University College of Medicine, Seoul, Korea
  • 6Department of Surgery, Koo Hospital, Daegu, Korea
  • 7Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

Abstract

Purpose
Ulcerative colitis (UC) is known to have an association with the increased risk of colorectal cancer (CRC), and UC-associated CRC does not follow the typical progress pattern of adenoma-carcinoma. The aim of this study is to investigate molecular characteristics of UC-associated CRC and further our understanding of the association between UC and CRC.
Methods
From 5 patients with UC-associated CRC, matched normal, dysplasia, and tumor specimens were obtained from formalin-fixed paraffin-embedded (FFPE) samples for analysis. Genomic DNA was extracted and whole exome sequencing was conducted to identify somatic variations in dysplasia and tumor samples. Statistical analysis was performed to identify somatic variations with significantly higher frequencies in dysplasia-initiated tumors, and their relevant functions were investigated.
Results
Total of 104 tumor mutation genes were identified with higher mutation frequencies in dysplasia-initiated tumors. Four of the 5 dysplasia-initiated tumors (80.0%) have TP53 mutations with frequent stop-gain mutations that were originated from matched dysplasia. APC and KRAS are known to be frequently mutated in general CRC, while none of the 5 patients have APC or KRAS mutation in their dysplasia and tumor samples. Glycoproteins including mucins were also frequently mutated in dysplasia-initiated tumors.
Conclusion
UC-associated CRC tumors have distinct mutational characteristics compared to typical adenoma-carcinoma tumors and may have different cancer-driving molecular mechanisms that are initiated from earlier dysplasia status.

Keyword

Ulcerative colitis; Colorectal neoplasms; Colitis-Associated Neoplasms; Genetic variation
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