講演情報
[P20-10]ETV6 germline pathogenic variantと大腸がん発がんリスクの関連
○土橋 映仁1,2,3, 冨樫 由紀1,2, 馬場 郷子1,2, 金子 景香3, 新川 裕美3, 幅野 愛理3, 竹内 賢吾1,2, 千野 晶子4, 河内 洋2, 植木 有紗3 (1.公益財団法人がん研究会 がん研究所 分子標的病理プロジェクト, 2.公益財団法人がん研究会 がん研究所 病理部, 3.公益財団法人がん研究会 がん研有明病院 臨床遺伝医療部, 4.公益財団法人がん研究会 がん研有明病院 下部消化管内科)
Heterozygous germline variants of the ETV6 gene are known to cause thrombocytopenia-5 (THC5), an autosomal dominant disorder characterized by decreased platelet count and bleeding tendency, leading to hematopoietic and solid tumors. ETV6 P214L, an ETV6 germline pathogenic variant, causes loss of protein function. This variant is possibly a dominant-negative form that binds to the normal ETV6 protein, inhibiting its function. We encountered a family having this ETV6 germline pathogenic variant. To determine whether ETV6 P214L is a risk factor for the colorectal polyposis and cancer in the patient and his family, we performed exome sequencing and RNA sequencing of the patient's colon cancer tissue and peripheral blood. By comparing the results of immunostaining of ETV6 between the colonic mucosa and the colon cancer tissue of the concerned patient and another patient who did not have the ETV6 germline variant, we investigated the involvement of the ETV6 germline variant in carcinogenesis through ETV6 protein localization. Weak nuclear staining in cells on the mucosal surface suggested that ETV6 may not be functioning correctly. Some cells also showed weak nuclear staining in the colorectal cancer tissue. In patients having ETV6 P214L, the ETV6 leaks from the nucleus and its function is impaired in affected tissues. ETV6 P214L possibly causes colorectal polyposis and cancer. Therefore, surveillance through colonoscopy may be considered in patients with a ETV6 germline pathogenic variant when ETV6 localization changes are observed in the nuclei of normal mucosa.