Elucidation of genes involved in the evolution of de novo colorectal cancer using next-generation sequencer

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K15670
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Experimental pathology
• Research Institution: Showa University
• Principal Investigator: Kouyama Yuta 昭和大学, 医学部, 助教 (40621719)
• Research Collaborator: Mimori Koshi
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: 陥凹型大腸癌 / 早期大腸癌 / 染色体増幅 / 次世代シークエンサー

Outline of Final Research Achievements

Recent studies have advocated that colorectal cancer might arise not only from polyp, but also from flat and depressed colorectal neoplasms (CRNs). Such depressed CRNs have been described as the most difficult lesions to detect endoscopically, presenting the highest risk of a malignant phenotype at the time of diagnosis. Clinicopathological and molecular features of depressed CRNs are not fully elucidated due to the scarcity of sample biopsies. Depressed type T1 CRCs showed a significantly malignant potential, and a lower rate of adenoma than those of flat and protruded types. We conducted whole exome and RNA sequencing for 19 depressed T1 CRCs. The rate of KRAS mutations was only 8.6% in depressed CRCs, while it was 50% in protruded CRCs. Amplification of chromosome 13 was higher in depressed CRCs than in protruded CRCs. The expression of genes related to angiogenesis and epithelial mesenchymal transition were higher in depressed CRCs than in protruded CRCs.

Free Research Field

医学

Academic Significance and Societal Importance of the Research Achievements

これまで、大腸癌の多くはポリープからできると考えられてきたが、ポリープからではなく、正常粘膜から発生するDe novo癌と考えられる陥凹型大腸癌が存在し、その臨床病理学的、分子生物学的悪性度の高さが示された。陥凹型大腸癌は、KRAS野生型だが癌の進展に大きく寄与する染色体増幅を早期より認めており、さらに癌の進行に寄与する上皮間葉転換や血管新生の遺伝子発現が上昇していることが示され、陥凹型大腸癌を発見することの重要性が示された。