CCNB2 and AURKA overexpression may cause atypical mitosis in Japanese cortisol-producing adrenocortical carcinoma with TP53 somatic variant

• Material Type: 博士論文
• ISSN: 1932-6203
• Title: CCNB2 and AURKA overexpression may cause atypical mitosis in Japanese cortisol-producing adrenocortical carcinoma with TP53 somatic variant
• Volume: 15 4
• Author/Editor: 池谷, 章
• Author Heading: 池谷, 章
• Publication, Distribution, etc.: Public Library of Science (PLoS)
• Publication Date: 2020-04-14
• Publication Date (W3CDTF): 2020-04-14
• Alternative Title: CCNB2とAURKAの過剰発現はTP53体細胞変異を有する日本人コルチゾール産生副腎皮質がんにおいて異常核分裂像を惹起する可能性がある
• Periodical title: PLOS ONE
• Degree grantor/type: 浜松医科大学
• Date Granted: 2021-03-16
• Date Granted (W3CDTF): 2021-03-16
• Dissertation Number: 甲第865号
• Degree Type: 博士（医学）
• Conferring No. (Dissertation): 甲第865号
• Text Language Code: eng
• Target Audience: 一般
• Note (General): doctoral; 医学系研究科; BackgroundMany genomic analyses of cortisol-producing adrenocortical carcinoma (ACC) have been reported, but very few have come from East Asia. The first objective of this study is to verify the genetic difference with the previous reports by analyzing targeted deep sequencing of 7 Japanese ACC cases using next-generation sequencing (NGS). The second objective is to compare the somatic variant findings identified by NGS analysis with clinical and pathological findings, aiming to acquire new knowledge about the factors that contribute to the poor prognosis of ACC and to find new targets for the treatment of ACC.MethodDNA was extracted from ACC tissue of seven patients and two reference blood samples. Targeted deep sequencing was performed using the MiSeq system for 12 genes, and the obtained results were analyzed using MuTect2. The hypothesis was obtained by integrating the somatic variant findings with clinical and pathological data, and it was further verified using The Cancer Genome Atlas (TCGA) dataset for ACC.ResultsSix possible pathogenic and one uncertain significance somatic variants including a novel PRKAR1A (NM_002734.4):c.545C>A (p.T182K) variant were found in five of seven cases. By integrating these data with pathological findings, we hypothesized that cases with TP53 variants were more likely to show atypical mitotic figures. Using TCGA dataset, we found that atypical mitotic figures were associated with TP53 somatic variant, and mRNA expression of CCNB2 and AURKA was significantly high in TP53 mutated cases and atypical mitotic figure cases.ConclusionWe believe this is the first report that discusses the relationship between atypical mitotic figures and TP53 somatic variant in ACC. We presumed that overexpression of CCNB2 and AURKA mRNA may cause atypical mitosis in TP53 somatic mutated cases. Because AURKA is highly expressed in atypical mitotic cases, it may be an appropriate indicator for AURKA inhibitors.
• DOI: info:doi/10.1371/journal.pone.0231665; https://doi.org/info:doi/10.1371/journal.pone.0231665
• Persistent ID (NDL): info:ndljp/pid/11720310; https://dl.ndl.go.jp/pid/11720310
• Collection: 障害者向け資料
• Collection (Materials For Handicapped People:1): テキストデータ
• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2021-09-06T03:11:00+09:00
• Date Created (W3CDTF): 2021-07-20
• Format (IMT): application/pdf
• Access Restrictions: 国立国会図書館内限定公開
• Service for the Digitized Contents Transmission Service: 図書館・個人送信対象外
• Availability of remote photoduplication service: 可
• Periodical Title (URI): http://hdl.handle.net/10271/00003873; https://hama-med.repo.nii.ac.jp/records/3747
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp

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