Analysis of responsible genes in early-onset colorectal cancer

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K08335
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human genetics
• Research Institution: Research Institute for Clinical Oncology, Saitama Cancer Center
• Principal Investigator: Akagi Kiwamu 埼玉県立がんセンター(臨床腫瘍研究所), 病院 腫瘍診断・予防科, 科長(兼)部長 (30244114)
• Co-Investigator(Kenkyū-buntansha): 角田 美穂 埼玉県立がんセンター(臨床腫瘍研究所), 病院 腫瘍診断・予防科, 研究員 (60347359)
• Research Collaborator: YAMAMOTO gou ; TAKAHASHI akemi
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: 若年がん / 大腸がん / シーケンス / DKC1

Outline of Final Research Achievements

Early-onset malignant tumors are supposed to have frequently genetic background. In recent study, some sort of pathogenic germline mutations were detected by 8.5% of patients affected malignant tumor under twenty. Moreover, even if limited to the colorectal cancer (CRC), 35% of the patients were diagnosed as hereditary colorectal cancer syndrome. These frequency in two studies was much higher than in the general population and both of them indicated many cases unrelated to familial history and phenotypes. Consequently, some genetic approach was recommended for juveniles affected cancer. In this study, based on the background, 10 cases of early-onset (under 40 years old) CRC was analyzed using RNA-Seq. As a result, compared with typical colon cancers, zinc finger protein family were expressed significantly higher. On the other hand, pathogenic germline mutations was found in DKC1.

Free Research Field

腫瘍遺伝学

Academic Significance and Societal Importance of the Research Achievements

本研究によって、若年の大腸がん患者においては家族歴やPhenotypeに関係無く、網羅的な遺伝子解析が必要である可能性が示唆された。今回検出されたDKC1遺伝子は、Dyskeratosis congenitaの原因遺伝子として知られており、発端者のバリアントはより重症例で発見されている。しかし、今回のケースは、貧血と大腸がんはあるものの、その他のPhenotypeが弱く、何年も原因が不明のままであった。本研究により、発端者はすでに死亡していたものの、血縁者に原因を明らかにすることができた。