BRCA1, BRCA2, and PALB2 are BRCA-pathway genes whose products are associated with homologous recombination repair of double strand breaks of DNA. Germline mutations of BRCA-pathway genes are known to elevate the risk for development of pancreatic cancer. However, BRCA-pathway gene mutations in tumors are associated with susceptibility to cisplatin and the poly ADP ribose inhibitor, which may have a dramatic therapeutic effect. We investigated BRCA-pathway gene mutations in sporadic pancreatic ductal adenocarcinomas (PDACs), familial PDACs, and pancreatic acinar cell carcinomas, and found that 2.4%, 9.3%, and 43% of sporadic PDACs, familial PDACs, and acinar cell carcinomas, respectively, harbored pathogenic mutations, i.e., frameshifts or nonsense mutations of BRCA-pathway genes. Patients with sporadic PDACs with pathogenic mutations and variants of unknown significance had longer survival than those with PDACs with benign variants or no mutations. Complete remission of multiple liver metastases from a pancreatic acinar cell carcinoma with a BRCA2 mutation by treatment with cisplatin was observed. Pancreatic cancers with BRCA-pathway gene mutations are likely to respond well to certain drugs, hence identifying patients with such tumors is particularly important in the era of genomic medicine.
"},{"@language":"ja","@value":"BRCA1，BRCA2，PALB2はBRCA経路遺伝子と呼ばれ，その産物はDNA二重鎖切断の相同組換え修復に関与する．BRCA経路遺伝子の生殖系列変異は膵癌発症のリスクを高め，また，BRCA経路遺伝子異常を持つ癌腫は白金系薬剤やPARP阻害剤に特異的に感受性が高く，臨床的に劇的な効果を見ることがある．我々は孤発性膵管癌，家族性膵癌，膵腺房細胞癌においてBRCA経路遺伝子変異を検索し，それぞれ2.4%，9.3%，43%に明らかな病原性変異を認めた．孤発性膵管癌例においては病原性あるいは効果不明のBRCA経路遺伝子変異を持つ患者群が有意に予後良好であった．また，BRCA経路遺伝子変異を持つ膵腺房細胞癌の多発肝転移がcisplatin投与で完全寛解した例を経験した．BRCA経路遺伝子変異を持つ膵腫瘍を見出すことは今後展開されるゲノム医療上極めて意義深いと考えられる．
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JPN. PANC. SOC."},{"@language":"ja","@value":"膵臓"}],"dc:publisher":[{"@language":"en","@value":"Japan Pancreas Society"},{"@language":"ja","@value":"一般社団法人 日本膵臓学会"}],"prism:publicationDate":"2018-12-25","prism:volume":"33","prism:number":"6","prism:startingPage":"944","prism:endingPage":"948"},"reviewed":"false","dcterms:accessRights":"http://purl.org/coar/access_right/c_abf2","url":[{"@id":"https://www.jstage.jst.go.jp/article/suizo/33/6/33_944/_pdf"},{"@id":"https://search.jamas.or.jp/link/ui/2019124598"}],"availableAt":"2018-12-25","foaf:topic":[{"@id":"https://cir.nii.ac.jp/all?q=%E8%86%B5%E8%87%93%E7%99%8C","dc:title":"膵臓癌"},{"@id":"https://cir.nii.ac.jp/all?q=%3Ci%3EBRCA1%3C/i%3E","dc:title":"BRCA1"},{"@id":"https://cir.nii.ac.jp/all?q=%3Ci%3EBRCA2%3C/i%3E","dc:title":"BRCA2"},{"@id":"https://cir.nii.ac.jp/all?q=%3Ci%3EPALB2%3C/i%3E","dc:title":"PALB2"},{"@id":"https://cir.nii.ac.jp/all?q=%E3%82%B2%E3%83%8E%E3%83%A0","dc:title":"ゲノム"},{"@id":"https://cir.nii.ac.jp/all?q=Pancreatic%20cancer","dc:title":"Pancreatic 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