{"id":"https://openalex.org/W4362567935","doi":"https://doi.org/10.1158/1541-7786.c.6539769.v1","title":"Data from Hypermutation of DPYD Deregulates Pyrimidine Metabolism and Promotes Malignant Progression","display_name":"Data from Hypermutation of DPYD Deregulates Pyrimidine Metabolism and Promotes Malignant Progression","publication_year":2023,"publication_date":"2023-04-03","ids":{"openalex":"https://openalex.org/W4362567935","doi":"https://doi.org/10.1158/1541-7786.c.6539769.v1"},"language":"en","primary_location":{"id":"doi:10.1158/1541-7786.c.6539769.v1","doi":"https://doi.org/10.1158/1541-7786.c.6539769.v1","is_oa":true,"landing_page_url":"https://doi.org/10.1158/1541-7786.c.6539769.v1","pdf_url":null,"source":null,"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"American Association for Cancer Research","raw_type":"posted-content"},"volume":null,"type":"other","indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"https://doi.org/10.1158/1541-7786.c.6539769.v1","any_repository_has_fulltext":null},"authorships":[{"author_position":"first","author":{"id":null,"display_name":"Lauren Edwards","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Lauren Edwards","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":null,"display_name":"Rohit Gupta","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Rohit Gupta","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"last","author":{"id":"https://openalex.org/A5047057665","display_name":"Fabian V. Filipp","orcid":"https://orcid.org/0000-0001-9889-5727","observed_orcids":["https://orcid.org/0000-0001-9889-5727"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Fabian Volker Filipp","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]}],"institutions":[],"countries_distinct_count":0,"institutions_distinct_count":0,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T12827","display_name":"Biochemical and Molecular Research","score":0.5839999914169312,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T12827","display_name":"Biochemical and Molecular Research","score":0.5839999914169312,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T11287","display_name":"Cancer Genomics and Diagnostics","score":0.04399999976158142,"subfield":{"id":"https://openalex.org/subfields/1306","display_name":"Cancer Research"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T11533","display_name":"Melanoma and MAPK Pathways","score":0.03139999881386757,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/dihydropyrimidine-dehydrogenase","display_name":"dihydropyrimidine dehydrogenase","score":0.9179999828338623},{"id":"https://openalex.org/keywords/somatic-mutations","display_name":"somatic mutations","score":0.7710000276565552},{"id":"https://openalex.org/keywords/pyrimidine-metabolism","display_name":"pyrimidine metabolism","score":0.9269999861717224},{"id":"https://openalex.org/keywords/cutaneous-melanoma","display_name":"cutaneous melanoma","score":0.8759999871253967},{"id":"https://openalex.org/keywords/metastatic-melanoma","display_name":"metastatic melanoma","score":0.7369999885559082},{"id":"https://openalex.org/keywords/malignant-progression","display_name":"malignant progression","score":0.8610000014305115},{"id":"https://openalex.org/keywords/gene-expression-signatures","display_name":"gene expression signatures","score":0.8240000009536743},{"id":"https://openalex.org/keywords/pyrimidine-salvage-pathway","display_name":"pyrimidine salvage pathway","score":0.6840000152587891},{"id":"https://openalex.org/keywords/nucleotide-biosynthesis","display_name":"nucleotide synthesis","score":0.7360000014305115},{"id":"https://openalex.org/keywords/protein-dimer-structure","display_name":"protein dimer structure","score":0.675000011920929},{"id":"https://openalex.org/keywords/ligand-binding-site","display_name":"ligand binding sites","score":0.8040000200271606}],"concepts":[{"id":"https://openalex.org/C2779655350","wikidata":"https://www.wikidata.org/wiki/Q1114455","display_name":"DPYD","level":5,"score":0.4928929805755615},{"id":"https://openalex.org/C153911025","wikidata":"https://www.wikidata.org/wiki/Q7202","display_name":"Molecular biology","level":1,"score":0.4614395499229431},{"id":"https://openalex.org/C200159599","wikidata":"https://www.wikidata.org/wiki/Q4893563","display_name":"Pyrimidine metabolism","level":4,"score":0.4168548583984375},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.41300103068351746},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.3998683989048004},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.3716496229171753},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.29862141609191895},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.2542528212070465},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.19250404834747314},{"id":"https://openalex.org/C135763542","wikidata":"https://www.wikidata.org/wiki/Q106016","display_name":"Genotype","level":3,"score":0.10974165797233582},{"id":"https://openalex.org/C181199279","wikidata":"https://www.wikidata.org/wiki/Q8047","display_name":"Enzyme","level":2,"score":0.08507797122001648},{"id":"https://openalex.org/C55775858","wikidata":"https://www.wikidata.org/wiki/Q1152227","display_name":"Pharmacogenetics","level":4,"score":0.06300917267799377},{"id":"https://openalex.org/C2776476023","wikidata":"https://www.wikidata.org/wiki/Q188261","display_name":"Purine","level":3,"score":0.06134313344955444}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1158/1541-7786.c.6539769.v1","doi":"https://doi.org/10.1158/1541-7786.c.6539769.v1","is_oa":true,"landing_page_url":"https://doi.org/10.1158/1541-7786.c.6539769.v1","pdf_url":null,"source":null,"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"American Association for Cancer Research","raw_type":"posted-content"}],"best_oa_location":{"id":"doi:10.1158/1541-7786.c.6539769.v1","doi":"https://doi.org/10.1158/1541-7786.c.6539769.v1","is_oa":true,"landing_page_url":"https://doi.org/10.1158/1541-7786.c.6539769.v1","pdf_url":null,"source":null,"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"American Association for Cancer Research","raw_type":"posted-content"},"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being","score":0.9537000060081482}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W2260446271","https://openalex.org/W2841467362","https://openalex.org/W2062110812","https://openalex.org/W4361939086","https://openalex.org/W4211051258","https://openalex.org/W4392681113","https://openalex.org/W7095199537","https://openalex.org/W1902640206","https://openalex.org/W2000075150","https://openalex.org/W2129191108"],"abstract_inverted_index":{"Abstract":[0],"New":[1],"strategies":[2],"are":[3,99,146],"needed":[4],"to":[5,18,44,62,106],"diagnose":[6],"and":[7,22,50,66,80,97,155,161,185],"target":[8],"human":[9,31],"melanoma.":[10],"To":[11],"this":[12],"end,":[13],"genomic":[14],"analyses":[15],"was":[16],"performed":[17],"assess":[19],"somatic":[20,103,124,175],"mutations":[21,104,125,143,176],"gene":[23,187],"expression":[24,188],"signatures":[25],"using":[26],"a":[27,119,171,180],"large":[28],"cohort":[29],"of":[30,58,113,122,135,144,150,177,189],"skin":[32],"cutaneous":[33],"melanoma":[34,73],"(SKCM)":[35],"patients":[36],"from":[37],"The":[38],"Cancer":[39,196],"Genome":[40],"Atlas":[41],"(TCGA)":[42],"project":[43],"identify":[45],"critical":[46],"differences":[47],"between":[48],"primary":[49],"metastatic":[51],"tumors.":[52],"Interestingly,":[53],"pyrimidine":[54,151,183,190],"metabolism":[55,184],"is":[56,164],"one":[57],"the":[59,69,107,114,127,133],"major":[60],"pathways":[61],"be":[63],"significantly":[64,100],"enriched":[65,101],"deregulated":[67],"at":[68],"transcriptional":[70],"level":[71],"in":[72,102,126,166,182],"progression.":[74,194],"In":[75],"addition,":[76],"dihydropyrimidine":[77],"dehydrogenase":[78],"(DPYD)":[79],"other":[81],"important":[82],"pyrimidine-related":[83],"genes:":[84],"DPYS,":[85],"AK9,":[86],"CAD,":[87],"CANT1,":[88],"ENTPD1,":[89],"NME6,":[90],"NT5C1A,":[91],"POLE,":[92],"POLQ,":[93],"POLR3B,":[94],"PRIM2,":[95],"REV3L,":[96],"UPP2":[98],"relative":[105],"background":[108],"mutation":[109],"rate.":[110],"Structural":[111],"analysis":[112],"DPYD":[115,145,178],"protein":[116,136],"dimer":[117],"reveals":[118],"potential":[120],"hotspot":[121],"recurring":[123],"ligand-binding":[128],"sites":[129],"as":[130,132],"well":[131],"interfaces":[134],"domains":[137],"that":[138],"mediated":[139],"electron":[140],"transfer.":[141],"Somatic":[142],"associated":[147],"with":[148],"upregulation":[149],"degradation,":[152],"nucleotide":[153,162],"synthesis,":[154],"nucleic":[156],"acid":[157],"processing":[158],"while":[159],"salvage":[160],"conversion":[163],"downregulated":[165],"TCGA":[167],"SKCM.":[168],"Implications:":[169],"At":[170],"systems":[172],"biology":[173],"level,":[174],"cause":[179],"switch":[181],"promote":[186],"enzymes":[191],"toward":[192],"malignant":[193],"Mol":[195],"Res;":[197],"14(2);":[198],"196\u2013206.":[199],"\u00a92015":[200],"AACR.":[201]},"counts_by_year":[],"updated_date":"2026-09-29T14:09:16.559479","created_date":"2023-04-06T00:00:00"}