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開催概要
開催回
第58回・2020年・京都
 

婦人科悪性腫瘍のクリニカルシークエンスで遭遇する生殖細胞系列変異への対応

演題番号 : WS1-2

[筆頭演者]
日下部 美佐子:1 
[共同演者]
谷川 道洋:1、織田 克利:2、稲葉 洋文:1、水野 祥:1、曾根 献文:1、鶴賀 哲史:1、牛久 綾:3、高阪 真路:4、油谷 浩幸:5、間野 博行:4、大須賀 穣:1、藤井 知行:1

1:東京大学附属病院・女性診療科・産科/女性外科、2:東京大学附属病院・ゲノム診療部、3:東京大学附属病院・病理部、4:東京大学・細胞情報学、5:東京大学先端科学技術研究センター・ゲノムサイエンス分野

 

Cancer multi-gene panel tests were now fundamental components of precision medicine, enabling the identification of genomic alterations for targeted therapy. For gynecological malignancies, germline variants are sometimes encountered and lead to the diagnosis of hereditary cancer, such as hereditary breast and ovarian cancer syndrome (HBOC) and Lynch syndrome. While the original purpose of these tests is to identify somatic variants, germline findings may also guide personalized therapy and are clinically significant for gynecological malignancies.
Between 2017 and 2018, we performed an original clinical sequence assay, named Todai OncoPanel for 23 cases of ovarian cancer and 17 cases of endometrial cancer. DNA isolated from tumor tissues and matched normal peripheral blood was subjected to deep-coverage NGS. Germline variants for hereditary cancer genes were returned to patients with prior written informed consents under the support of genetic counselors.
Secondary germline variants were detected in 10 ovarian cancer cases and 6 endometrial cancer cases. After analyzing the pathogenicity by multiple public databases, 4 BRCA genes variants and 2 MMR genes variants were determined pathogenic and disclosed to patients. As for cases with variants of uncertain significance (VUS), we individually discussed the possibility of pathogenicity considering their family history and predicable functions of the variants and disclosed 1 BRCA VUS and 2 MMR genes VUS.
For cancer multi-gene tests of gynecologic malignancies, germline secondary findings are frequently encountered, suggesting that genetic counseling of hereditary cancer might be necessary prior to the test. Still, public databases are lacking the information of Japanese unique variants, and we have to carefully and individually discuss the possibility of pathogenicity for cases with germline VUS. The nation-wide knowledge databases with enriched information about Japanese unique variants is now needed.

キーワード

臓器別:卵巣

手法別:ゲノム・遺伝子

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