論文 - 詳細
| RRC ID | 58370 |
|---|---|
| 著者 | Inoue S, Hirota Y, Ueno T, Fukui Y, Yoshida E, Hayashi T, Kojima S, Takeyama R, Hashimoto T, Kiyono T, Ikemura M, Taguchi A, Tanaka T, Tanaka Y, Sakata S, Takeuchi K, Muraoka A, Osuka S, Saito T, Oda K, Osuga Y, Terao Y, Kawazu M, Mano H. |
| タイトル | Uterine adenomyosis is an oligoclonal disorder associated with KRAS mutations. |
| ジャーナル | Nat Commun |
| Abstract |
Uterine adenomyosis is a benign disorder that often co-occurs with endometriosis and/or leiomyoma, and impairs quality of life. The genomic features of adenomyosis are unknown. Here we apply next-generation sequencing to adenomyosis (70 individuals and 192 multi-regional samples), as well as co-occurring leiomyoma and endometriosis, and find recurring KRAS mutations in 26/70 (37.1%) of adenomyosis cases. Multi-regional sequencing reveals oligoclonality in adenomyosis, with some mutations also detected in normal endometrium and/or co-occurring endometriosis. KRAS mutations are more frequent in cases of adenomyosis with co-occurring endometriosis, low progesterone receptor (PR) expression, or progestin (dienogest; DNG) pretreatment. DNG's anti-proliferative effect is diminished via epigenetic silencing of PR in immortalized cells with mutant KRAS. Our genomic analyses suggest that adenomyotic lesions frequently contain KRAS mutations that may reduce DNG efficacy, and that adenomyosis and endometriosis may share molecular etiology, explaining their co-occurrence. These findings could lead to genetically guided therapy and/or relapse risk assessment after uterine-sparing surgery. |
| 巻・号 | 10(1) |
| ページ | 5785 |
| 公開日 | 2019-12-19 |
| DOI | 10.1038/s41467-019-13708-y |
| PII | 10.1038/s41467-019-13708-y |
| PMID | 31857578 |
| PMC | PMC6923389 |
| MeSH | Adenomyosis / complications Adenomyosis / genetics* Adenomyosis / therapy Adult Cell Proliferation / drug effects Cell Proliferation / genetics DNA Mutational Analysis Endometriosis / complications Endometriosis / genetics* Endometriosis / therapy Endometrium / pathology Endometrium / surgery Female High-Throughput Nucleotide Sequencing Humans Hysterectomy Middle Aged Mutation Myometrium / pathology Myometrium / surgery Nandrolone / analogs & derivatives* Nandrolone / pharmacology Nandrolone / therapeutic use Proto-Oncogene Proteins p21(ras) / genetics* Receptors, Progesterone / genetics Receptors, Progesterone / metabolism Treatment Outcome Young Adult |
| IF | 12.121 |
| 引用数 | 2 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 16 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 遺伝子材料 | CSII-CMV-RfA (RDB04386) pCMV-VSV-G-RSV-Rev (RDB04393) pCAG-HIVgp (RDB04394) |