Classification of Colorectal Cancer based on genetic alterations

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10630
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kyoto University
• Principal Investigator: Sakai Yoshiharu 京都大学, 医学研究科, 教授 (60273455)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 大腸癌 / 次世代シーケンサー

Outline of Final Research Achievements

We performed targeted capture sequencing on DNA extracted from colorectal cancer (CRC) samples to investigate somatic mutations. Colorectal cancer can be divided into 2 major categories, which are hypermutated CRC and nonhypermutated CRC. Among hypermutated CRC, further investigation enabled us to detect a distinct subtype with characteristic POLE gene mutations (POLE-CRC), which can be clearly distinguished from microsatellite instable CRC (MSI-CRC). POLE gene encode polymerase epsilon, which is one of the key polymerases used in DNA replication.
Only 1.5% of all CRC is POLE-CRC, which is the reason why it was previously difficult to clarify their clinical and genetic characteristics. In our large cohort, we have shown for the first time, that POLE-CRC have a significantly better prognosis than nonhypermutated CRC and MSI-CRC. Also, POLE-CRC is diagnosed mainly in their 40s and 50s, which is significantly younger than nonhypermutated CRC and MSI-CRC.

Free Research Field

消化器外科学

Academic Significance and Societal Importance of the Research Achievements

POLE遺伝子変異を特徴とする大腸癌（POLE-CRC）を同定した。稀な腫瘍であるために、現在までにその遺伝子変異プロファイルや臨床病理学的特徴を明らかにした報告は認めていない。
POLE-CRCは若年発症するが、予後は非常に良好である。若年発症した悪性腫瘍に対しては、一般的に、侵襲の強いadjuvant therapyやneoadjuvant therapyが勧められる傾向にあるが、POLE-CRCである事が診断できれば、手術のみで完治が高い確率で見込める事が予想できる様になる。不要な抗がん剤や放射線治療を減らす事ができると考えられる。