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DOI | 10.1126/science.aau6509 |
Human tumor genomics and zebrafish modeling identify SPRED1 loss as a driver of mucosal melanoma | |
Ablain, Julien1,2,3; Xu, Mengshu4,5; Rothschild, Harriet1,2,3; Jordan, Richard C.4,6,7; Mito, Jeffrey K.1,2,3,8; Daniels, Brianne H.4,6; Bell, Caitlin F.9; Joseph, Nancy M.6; Wu, Hong10; Bastian, Boris C.4,5; Zon, Leonard I.1,2,3,11,12,13; Yeh, Iwei4,5 | |
2018-11-30 | |
发表期刊 | SCIENCE |
ISSN | 0036-8075 |
EISSN | 1095-9203 |
出版年 | 2018 |
卷号 | 362期号:6418页码:1055-+ |
文章类型 | Article |
语种 | 英语 |
国家 | USA |
英文摘要 | Melanomas originating from mucosal surfaces have low mutation burden, genomic instability, and poor prognosis. To identify potential driver genes, we sequenced hundreds of cancer-related genes in 43 human mucosal melanomas, cataloging point mutations, amplifications, and deletions. The SPRED1 gene, which encodes a negative regulator of mitogen-activated protein kinase (MAPK) signaling, was inactivated in 37% of the tumors. Four distinct genotypes were associated with SPRED1 loss. Using a rapid, tissue-specific CRISPR technique to model these genotypes in zebrafish, we found that SPRED1 functions as a tumor suppressor, particularly in the context of KIT mutations. SPRED1 knockdown caused MAPK activation, increased cell proliferation, and conferred resistance to drugs inhibiting KIT tyrosine kinase activity. These findings provide a rationale for MAPK inhibition in SPRED1-deficient melanomas and introduce a zebrafish modeling approach that can be used more generally to dissect genetic interactions in cancer. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000451609000046 |
WOS关键词 | TERT PROMOTER MUTATIONS ; KIT GENE MUTATION ; BRAF MUTATIONS ; ONCOGENIC MUTATIONS ; MALIGNANT-MELANOMA ; LEGIUS SYNDROME ; WHOLE-GENOME ; NRAS ; ACTIVATION ; PROTEIN |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/200192 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.Boston Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA; 2.Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA; 3.Dana Farber Canc Inst, Boston, MA 02115 USA; 4.Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94158 USA; 5.Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA; 6.Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA; 7.Univ Calif San Francisco, Dept Orofacial Sci, San Francisco, CA 94143 USA; 8.Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA; 9.Stanford Univ, Dept Med, Med Ctr, Stanford, CA 94305 USA; 10.Fox Chase Canc Ctr, 7701 Burholme Ave, Philadelphia, PA 19111 USA; 11.Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA; 12.Boston Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA; 13.Harvard Univ, Boston, MA 02115 USA |
推荐引用方式 GB/T 7714 | Ablain, Julien,Xu, Mengshu,Rothschild, Harriet,et al. Human tumor genomics and zebrafish modeling identify SPRED1 loss as a driver of mucosal melanoma[J]. SCIENCE,2018,362(6418):1055-+. |
APA | Ablain, Julien.,Xu, Mengshu.,Rothschild, Harriet.,Jordan, Richard C..,Mito, Jeffrey K..,...&Yeh, Iwei.(2018).Human tumor genomics and zebrafish modeling identify SPRED1 loss as a driver of mucosal melanoma.SCIENCE,362(6418),1055-+. |
MLA | Ablain, Julien,et al."Human tumor genomics and zebrafish modeling identify SPRED1 loss as a driver of mucosal melanoma".SCIENCE 362.6418(2018):1055-+. |
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