Identification of actionable genetic alteration for grade 3 endomtrial endometrioid carcinoma

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K18207
• 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: National Cancer Center Japan
• Principal Investigator: Kato Mayumi 国立研究開発法人国立がん研究センター, 中央病院, 医員 (90869893)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: CTNNB1変異 / ProMisE study

Outline of Final Research Achievements

To identify prognostic factors in patients with grade 3 endometrial endometrioid carcinoma (G3 EEC), we evaluated the spectrum of genomic alterations and examined whether previously reported molecular subtypes of endometrial carcinoma were adapted to clinical outcome prediction. We classified the patients into four risk groups of the disease based on the ProMisE. Genomic alterations in PTEN, ARID1A, TP53, and PIK3CA were detected in more than 30% of the patients. Overall survival and recurrence-free survival of patients with genomic alterations in CTNNB1 were poorer than those of patients with wild-type CTNNB1. Compared with that of alterations prevalent in Caucasians, the frequency of genomic alterations in POLE and TP53 was higher in our study than in The Cancer Genome Atlas dataset. The CTNNB1 mutation is a potential novel biomarker for the prognosis of patients with G3EEC, and prognosis classification using ProMisE may help screen Japanese patients with the disease.

Free Research Field

婦人科腫瘍

Academic Significance and Societal Importance of the Research Achievements

国外ではTCGAによる全エクソンシークエンスといった大規模ゲノム解析が既に行われており,欧米では既に遺伝子パネル検査が日常診療として実施されており,十万人レベルでの ゲノムデータがGENIEなどに公開されている.しかし,近年増加傾向にある日本人子宮体がんに対するゲノム解析はほとんど行われておらず,令和元年から始まった遺伝子パネル検査は全国でも月数百例と欧米と同等のレベルになるにはまだ年月を必要としている.本研究は日本人に対するゲノム医療を推進させるための重要な研究データとなり得た.子宮体癌Grade3の中でも特に予後不良な集団が分子標的薬の恩恵を受けられる可能性が示唆された.