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

池谷, 章

doi:https://doi.org/10.1371/journal.pone.0231665

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

http://hdl.handle.net/10271/00003873

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論文本文 (1.9 MB)

Item type

学位論文 / Thesis or Dissertation(1)

公開日

2021-08-01

タイトル

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

言語

eng

資源タイプ

資源タイプ識別子

http://purl.org/coar/resource_type/c_db06

資源タイプ

doctoral thesis

アクセス権

open access

アクセス権URI

http://purl.org/coar/access_right/c_abf2

その他のタイトル

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

著者

池谷, 章

書誌情報

en : PLOS ONE

巻 15, 号 4, p. e0231665, 発行日 2020-04-14

出版者

Public Library of Science (PLoS)

言語

権利

言語

権利情報

Copyright 2020 Ikeya et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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内容記述タイプ

Abstract

内容記述

Background
Many 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.
Method
DNA 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.
Results
Six 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.
Conclusion
We 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.

言語

学位名

博士（医学）

学位の区分

内容記述

doctoral

学位の分野

内容記述

医学系研究科

学位授与機関

学位授与機関識別子Scheme

kakenhi

学位授与機関識別子

13802

学位授与機関名

浜松医科大学

学位授与年月日

2021-03-16

学位授与番号

甲第865号

EISSN

収録物識別子タイプ

EISSN

収録物識別子

1932-6203

PubMed番号

識別子タイプ

PMID

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2023-06-20 16:26:07.394085

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

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