molecular and epidemiological analysis for new carcinogenesis mechanism in hereditary gynecological cancer

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K16812
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Keio University
• Principal Investigator: Tsuji Kosuke 慶應義塾大学, 医学部(信濃町), 助教 (70528166)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: リンチ症候群 / 卵巣癌 / 子宮体癌 / 重複癌 / マイクロサテライト不安定性 / 高腫瘍変異量

Outline of Final Research Achievements

The characteristic feature of Lynch syndrome, one of a hereditary gynecological tumors, is microsatellite instability (MSI), which has been attracting attention as a companion diagnostics for immune checkpoint inhibitors. We proved the usefulness of the SGO criteria as a diagnostic tool for Lynch syndrome in ovarian cancer. In addition, Lynch syndrome is common in 7/33 (21.2%) cases of double cancer of ovarian and endometrial cancer. In addition, genomic analysis of these tumors revealed tumor mutation burden-high (> 10 mutations/ Mb) in both endometrial cancer and ovarian cancer. Further analysis of these mutated genes is expected to reveal the carcinogenic mechanism of each primary cancer. In addition, MSI analysis of advanced or recurrent gynecological cancers showed that MSI-high was not observed in cervical cancer.

Free Research Field

婦人科腫瘍

Academic Significance and Societal Importance of the Research Achievements

近年の研究によって、遺伝性腫瘍は比較的一般的な頻度で認められることが分かってきており、本研究によって、遺伝性腫瘍であるリンチ症候群が、卵巣癌、特に卵巣癌子宮体癌の重複例において高率に認められることが分かり、婦人科癌診療における遺伝的関与の可能性に注意すべきであることを示している。また、治療選択におけるMSI検査においても、子宮体癌、卵巣癌において陽性結果が多く、若年者にも多い子宮頸癌における遺伝性の関与が少ないことが示され、社会的にインパクトがあると考える。