{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Ablain J"],"funding":["The Ellison Foundation","Melanoma Research Foundation","Howard Hughes Medical Institute","NHLBI NIH HHS","National Cancer Institute","Melanoma Research Alliance","NCI NIH HHS","Dermatology Foundation","National Institutes of Health","V Foundation for Cancer Research","Terry Patters Melanoma Foundation"],"pagination":["1055-1060"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6475924"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["362(6418)"],"pubmed_abstract":["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 <i>SPRED1</i> 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 <i>SPRED1</i> loss. Using a rapid, tissue-specific CRISPR technique to model these genotypes in zebrafish, we found that <i>SPRED1</i> functions as a tumor suppressor, particularly in the context of <i>KIT</i> mutations. <i>SPRED1</i> knockdown caused MAPK activation, increased cell proliferation, and conferred resistan"],"journal":["Science (New York, N.Y.)"],"pubmed_title":["Human tumor genomics and zebrafish modeling identify &lt;i&gt;SPRED1&lt;/i&gt; loss as a driver of mucosal melanoma."],"pmcid":["PMC6475924"],"funding_grant_id":["R35 CA220481","K99CA201465","T32 HL007627","P01 CA163222","R01 CA103846","U24CA196067","K99 CA201465","1R35CA220481","U24 CA196067","R01CA103846"],"pubmed_authors":["Yeh I","Xu M","Jordan RC","Rothschild H","Bastian BC","Zon LI","Ablain J","Mito JK","Bell CF","Joseph NM","Daniels BH","Wu H"],"additional_accession":[]},"is_claimable":false,"name":"Human tumor genomics and zebrafish modeling identify &lt;i&gt;SPRED1&lt;/i&gt; loss as a driver of mucosal melanoma.","description":"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 <i>SPRED1</i> 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 <i>SPRED1</i> loss. Using a rapid, tissue-specific CRISPR technique to model these genotypes in zebrafish, we found that <i>SPRED1</i> functions as a tumor suppressor, particularly in the context of <i>KIT</i> mutations. <i>SPRED1</i> knockdown caused MAPK activation, increased cell proliferation, and conferred resistan","dates":{"release":"2018-01-01T00:00:00Z","publication":"2018 Nov","modification":"2026-05-04T21:04:27.035Z","creation":"2019-06-06T22:47:03Z"},"accession":"S-EPMC6475924","cross_references":{"pubmed":["30385465"],"doi":["10.1126/science.aau6509"]}}