論文 - 詳細
| RRC ID | 54015 |
|---|---|
| 著者 | Hillman RT, Celestino J, Terranova C, Beird HC, Gumbs C, Little L, Nguyen T, Thornton R, Tippen S, Zhang J, Lu KH, Gershenson DM, Rai K, Broaddus RR, Futreal PA. |
| タイトル | KMT2D/MLL2 inactivation is associated with recurrence in adult-type granulosa cell tumors of the ovary. |
| ジャーナル | Nat Commun |
| Abstract |
Adult-type granulosa cell tumors of the ovary (aGCTs) are rare gynecologic malignancies that exhibit a high frequency of somatic FOXL2 c.C402G (p.Cys134Trp) mutation. Treatment of relapsed aGCT remains a significant clinical challenge. Here we show, using whole-exome and cancer gene panel sequencing of 79 aGCTs from two independent cohorts, that truncating mutation of the histone lysine methyltransferase gene KMT2D (also known as MLL2) is a recurrent somatic event in aGCT. Mono-allelic KMT2D-truncating mutations are more frequent in recurrent (10/44, 23%) compared with primary (1/35, 3%) aGCTs (p = 0.02, two-sided Fisher's exact test). IHC detects additional non-KMT2D-mutated aGCTs with loss of nuclear KMT2D expression, suggesting that non-genetic KMT2D inactivation may occur in this tumor type. These findings identify KMT2D inactivation as a novel driver event in aGCTs and suggest that mutation of this gene may increase the risk of disease recurrence. |
| 巻・号 | 9(1) |
| ページ | 2496 |
| 公開日 | 2018-6-27 |
| DOI | 10.1038/s41467-018-04950-x |
| PII | 10.1038/s41467-018-04950-x |
| PMID | 29950560 |
| PMC | PMC6021426 |
| MeSH | Adult Aged Alleles Cell Nucleus / metabolism DNA-Binding Proteins / genetics* DNA-Binding Proteins / metabolism Exome Sequencing Female Granulosa Cell Tumor / genetics* Granulosa Cell Tumor / pathology Humans Middle Aged Mutation Neoplasm Proteins / genetics* Neoplasm Proteins / metabolism Neoplasm Recurrence, Local / genetics* Neoplasm Recurrence, Local / pathology Ovarian Neoplasms / genetics* Ovarian Neoplasms / pathology Ovary / cytology Ovary / pathology Retrospective Studies |
| IF | 12.121 |
| 引用数 | 10 |
| 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 | X(Twitter) |
| 各媒体での言及数の合計 | 10 |
| 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 | |
| ヒト・動物細胞 | KGN(RCB1154) |