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Mutational landscape of T-cell lymphoma in mice lacking the DNA mismatch repair gene Mlh1: no synergism with ionizing radiation
https://repo.qst.go.jp/records/49500
https://repo.qst.go.jp/records/495001b9e30a1-cfca-44da-9550-051128aaff7d
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2019-01-23 | |||||
| タイトル | ||||||
| タイトル | Mutational landscape of T-cell lymphoma in mice lacking the DNA mismatch repair gene Mlh1: no synergism with ionizing radiation | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
| 資源タイプ | journal article | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Daino, Kazuhiro
× Daino, Kazuhiro× Ishikawa, Atsuko× Suga, Tomo× Amasaki, Yoshiko× Kodama, Yotaro× Shang, Yi× Shinobu, Hirano-Sakairi× Nishimura, Mayumi× Nakata, Akifumi× Yoshida, Mitsuaki× Imai, Takashi× Shimada, Yoshiya× Kakinuma, Shizuko× Daino, Kazuhiro× Ishikawa, Atsuko× Suga, Tomo× Amasaki, Yoshiko× Shang, Yi× Nishimura, Mayumi× Imai, Takashi× Shimada, Yoshiya× Kakinuma, Shizuko |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Biallelic germline mutations in the DNA mismatch repair gene MLH1 lead to constitutional mismatch repair–deficiency syndrome and an increased risk for childhood hematopoietic malignancies, including lymphoma and leukemia. To examine how Mlh1 dysfunction promotes lymphoma as well as the influence of ionizing radiation (IR) exposure, we used a Mlh1–/– mouse model and whole-exome sequencing to assess genomic alterations in 23 T-cell lymphomas, including 8 spontaneous and 15 IR-associated lymphomas. Exposure to IR accelerated T-cell lymphoma induction in the Mlh1–/– mice, and whole-exome sequencing revealed that IR exposure neither increased the number of mutations nor altered the mutation spectrum of the lymphomas. Frequent mutations were evident in genes encoding transcription factors (e.g. Ikzf1, Trp53, Bcl11b), epigenetic regulators (e.g. Suv420h1, Ep300, Kmt2d), transporters (e.g. Rangap1, Kcnj16), extracellular matrix (e.g. Megf6, Lrig1), cell motility (e.g. Argef19, Dnah17), protein kinase cascade (e.g. Ptpro, Marcks) and in genes involved in NOTCH (e.g. Notch1), and PI3K/AKT (e.g. Pten, Akt2) signaling pathways in both spontaneous and IR-associated lymphomas. Frameshift mutations in mononucleotide repeat sequences within the genes Trp53, Ep300, Kmt2d, Notch1, Pten and Marcks were newly identified in the lymphomas. The lymphomas also exhibited a few chromosomal abnormalities. The results establish a landscape of genomic alterations in spontaneous and IR-associated lymphomas that occur in the context of mismatch repair dysfunction and suggest potential targets for cancer treatment. | |||||
| 書誌情報 |
Carcinogenesis 巻 40, 号 2, p. 216-224, 発行日 2019-02 |
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| 出版者 | ||||||
| 出版者 | Oxford University Press | |||||
| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 0143-3334 | |||||
| PubMed番号 | ||||||
| 識別子タイプ | PMID | |||||
| 関連識別子 | 30721949 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1093/carcin/bgz013 | |||||
| 関連サイト | ||||||
| 識別子タイプ | URI | |||||
| 関連識別子 | https://academic.oup.com/carcin/article/40/2/216/5306484 | |||||
