{"id":"https://openalex.org/W2887555917","doi":"https://doi.org/10.1158/1538-7445.am2018-2307","title":"Abstract 2307: Differential effects of N-terminal vs C-terminal truncating CDKN1A mutations on cisplatin resistance in bladder cancer","display_name":"Abstract 2307: Differential effects of N-terminal vs C-terminal truncating CDKN1A mutations on cisplatin resistance in bladder cancer","publication_year":2018,"publication_date":"2018-07-01","ids":{"openalex":"https://openalex.org/W2887555917","doi":"https://doi.org/10.1158/1538-7445.am2018-2307","mag":"2887555917"},"language":"en","primary_location":{"id":"doi:10.1158/1538-7445.am2018-2307","doi":"https://doi.org/10.1158/1538-7445.am2018-2307","is_oa":false,"landing_page_url":"https://doi.org/10.1158/1538-7445.am2018-2307","pdf_url":null,"source":{"id":"https://openalex.org/S168522863","display_name":"Cancer Research","issn_l":"0008-5472","issn":["0008-5472","1538-7445"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320273","host_organization_name":"American Association for Cancer Research","host_organization_lineage":["https://openalex.org/P4310320273"],"host_organization_lineage_names":["American Association for Cancer Research"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Cancer Research","raw_type":"journal-article"},"volume":null,"type":"conference-abstract","indexed_in":["crossref"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5040749329","display_name":"Rahmat K. Sikder","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I1289437631","display_name":"Fox Chase Cancer Center","ror":"https://ror.org/0567t7073","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1289437631","https://openalex.org/I4210122924"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Rahmat K. Sikder","raw_affiliation_strings":["Fox Chase Cancer Center, Philadelphia, PA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Fox Chase Cancer Center, Philadelphia, PA","institution_ids":["https://openalex.org/I1289437631"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5075201353","display_name":"Wafik S. El\u2010Deiry","orcid":"https://orcid.org/0000-0002-9577-8266","observed_orcids":["https://orcid.org/0000-0002-9577-8266"]},"institutions":[{"id":"https://openalex.org/I1289437631","display_name":"Fox Chase Cancer Center","ror":"https://ror.org/0567t7073","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1289437631","https://openalex.org/I4210122924"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Wafik S. El-Deiry","raw_affiliation_strings":["Fox Chase Cancer Center, Philadelphia, PA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Fox Chase Cancer Center, Philadelphia, PA","institution_ids":["https://openalex.org/I1289437631"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5011122559","display_name":"Philip H. Abbosh","orcid":"https://orcid.org/0000-0003-3611-9532","observed_orcids":["https://orcid.org/0000-0003-3611-9532"]},"institutions":[{"id":"https://openalex.org/I1289437631","display_name":"Fox Chase Cancer Center","ror":"https://ror.org/0567t7073","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1289437631","https://openalex.org/I4210122924"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Philip H. Abbosh","raw_affiliation_strings":["Fox Chase Cancer Center, Philadelphia, PA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Fox Chase Cancer Center, Philadelphia, PA","institution_ids":["https://openalex.org/I1289437631"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":[],"corresponding_institution_ids":["https://openalex.org/I1289437631"],"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":"78","issue":"13_Supplement","first_page":"2307","last_page":"2307"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10458","display_name":"Bladder and Urothelial Cancer Treatments","score":0.6615999937057495,"subfield":{"id":"https://openalex.org/subfields/2746","display_name":"Surgery"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10458","display_name":"Bladder and Urothelial Cancer Treatments","score":0.6615999937057495,"subfield":{"id":"https://openalex.org/subfields/2746","display_name":"Surgery"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10583","display_name":"Cancer-related Molecular Pathways","score":0.2863999903202057,"subfield":{"id":"https://openalex.org/subfields/2730","display_name":"Oncology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10123","display_name":"DNA Repair Mechanisms","score":0.02459999918937683,"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/p21","display_name":"p21","score":0.8399999737739563},{"id":"https://openalex.org/keywords/truncating-variants","display_name":"truncating mutations","score":0.7519999742507935},{"id":"https://openalex.org/keywords/cisplatin-resistance","display_name":"cisplatin resistance","score":0.949999988079071},{"id":"https://openalex.org/keywords/bladder-cancer","display_name":"bladder cancer","score":0.972000002861023},{"id":"https://openalex.org/keywords/dna-polymerase-eta","display_name":"DNA polymerase eta","score":0.8809999823570251},{"id":"https://openalex.org/keywords/translesion-synthesis","display_name":"translesion synthesis","score":0.8460000157356262},{"id":"https://openalex.org/keywords/dna-damage-tolerance","display_name":"DNA damage tolerance","score":0.9599999785423279},{"id":"https://openalex.org/keywords/s-phase-arrest","display_name":"S phase arrest","score":0.8309999704360962},{"id":"https://openalex.org/keywords/cyclin-d1","display_name":"cyclin D1","score":0.843999981880188}],"concepts":[{"id":"https://openalex.org/C2778239845","wikidata":"https://www.wikidata.org/wiki/Q412415","display_name":"Cisplatin","level":3,"score":0.853186845779419},{"id":"https://openalex.org/C34688535","wikidata":"https://www.wikidata.org/wiki/Q418732","display_name":"Proliferating cell nuclear antigen","level":3,"score":0.751291036605835},{"id":"https://openalex.org/C29537977","wikidata":"https://www.wikidata.org/wiki/Q188941","display_name":"Cell cycle","level":3,"score":0.5283843874931335},{"id":"https://openalex.org/C153911025","wikidata":"https://www.wikidata.org/wiki/Q7202","display_name":"Molecular biology","level":1,"score":0.5047632455825806},{"id":"https://openalex.org/C105696609","wikidata":"https://www.wikidata.org/wiki/Q1068809","display_name":"Cell cycle checkpoint","level":4,"score":0.5026590824127197},{"id":"https://openalex.org/C134935766","wikidata":"https://www.wikidata.org/wiki/Q210538","display_name":"DNA repair","level":3,"score":0.49997711181640625},{"id":"https://openalex.org/C143425029","wikidata":"https://www.wikidata.org/wiki/Q5205747","display_name":"DNA damage","level":3,"score":0.4930259883403778},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.4464944899082184},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.4267405569553375},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.3768354058265686},{"id":"https://openalex.org/C552990157","wikidata":"https://www.wikidata.org/wiki/Q7430","display_name":"DNA","level":2,"score":0.35115158557891846},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.34736132621765137},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.3261607587337494},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.15980926156044006},{"id":"https://openalex.org/C2776694085","wikidata":"https://www.wikidata.org/wiki/Q974135","display_name":"Chemotherapy","level":2,"score":0.11449116468429565}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1158/1538-7445.am2018-2307","doi":"https://doi.org/10.1158/1538-7445.am2018-2307","is_oa":false,"landing_page_url":"https://doi.org/10.1158/1538-7445.am2018-2307","pdf_url":null,"source":{"id":"https://openalex.org/S168522863","display_name":"Cancer Research","issn_l":"0008-5472","issn":["0008-5472","1538-7445"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320273","host_organization_name":"American Association for Cancer Research","host_organization_lineage":["https://openalex.org/P4310320273"],"host_organization_lineage_names":["American Association for Cancer Research"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Cancer Research","raw_type":"journal-article"}],"best_oa_location":null,"sustainable_development_goals":[{"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3","score":0.9476000070571899}],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W3109759561","https://openalex.org/W2741570237","https://openalex.org/W7117996267","https://openalex.org/W3113031067","https://openalex.org/W4407088814","https://openalex.org/W3043012216","https://openalex.org/W2147531617","https://openalex.org/W4281635146","https://openalex.org/W7155899698","https://openalex.org/W2232724817"],"abstract_inverted_index":{"Abstract":[0],"Introduction":[1],"Approximately":[2],"15%":[3],"of":[4,25,36,139,168,193,202,254,263,357,384,419,472,488],"muscle":[5],"invasive":[6],"bladder":[7,455,483],"cancers":[8],"harbor":[9],"mutations":[10,478],"in":[11,89,213,237,245,266,271,278,283,301,308,312,327,354,368,402,406,422,453,482],"the":[12,17,23,28,54,59,77,137,140,144,146,163,200,304,342,346,355,394,438,489],"CDKN1A":[13,477],"gene,":[14],"which":[15],"encodes":[16],"p53":[18,112],"target":[19,121,153],"gene":[20],"p21,":[21,360],"with":[22,165,188,378],"majority":[24,138],"alterations":[26],"truncating":[27,476],"peptide.":[29,396],"We":[30,49,97,161,182],"previously":[31],"found":[32],"that":[33,51,362],"proximal":[34],"truncation":[35],"p21":[37,114,363,377,442],"sensitized":[38],"cells":[39,164,343,408],"to":[40,67,109,120,132,152,229,235,243,249,393,436],"cisplatin,":[41],"while":[42],"distal":[43],"truncations":[44,52],"made":[45],"them":[46],"more":[47,388],"resistant.":[48],"hypothesized":[50],"preserving":[53],"CDKi":[55,380],"domain":[56,62,381],"but":[57,70,220],"ablating":[58],"PCNA":[60,69,145,447],"binding":[61,147],"would":[63,434],"abrogate":[64],"p21's":[65],"ability":[66],"sequester":[68],"maintain":[71],"cell":[72,100,186,286,347,372,457],"cycle":[73,230,373],"arrest":[74,223,236,244,256,326,337,350,391],"capacities,":[75],"enhancing":[76],"interaction":[78],"between":[79,441],"mono-ubiquitiniated-PCNA":[80],"(ub-PCNA)":[81],"and":[82,92,111,113,125,128,135,170,180,198,205,217,227,268,274,341,387,414,427,443,448],"DNA":[83,93,403],"polymerase":[84],"eta":[85],"(Pol":[86],"\u03b7),":[87],"resulting":[88],"increased":[90,295],"TLS":[91,397,426],"damage":[94,404],"tolerance.":[95],"Methods":[96],"used":[98,131,156],"SW780":[99,407],"line":[101],"for":[102,195,446,492],"this":[103,222,336,451],"study":[104],"based":[105],"on":[106,479],"its":[107],"resistance":[108,481],"cisplatin":[110,169,194,292,299,429,480],"WT":[115],"status.":[116],"CRISPR":[117],"sgRNAs":[118],"designed":[119,151],"amino":[122],"acids":[123],"12":[124],"109":[126],"(SW780-sg12":[127],"SW780-sg109)":[129],"were":[130,233,241],"introduce":[133],"frameshifts":[134],"disrupt":[136],"peptide":[141],"or":[142],"only":[143],"domain,":[148],"respectively.":[149],"sgRNA":[150],"GFP":[154],"was":[155,257,306,317],"as":[157,409],"a":[158,279,358,365,400],"control":[159],"(sgGFP).":[160],"treated":[162,183],"GI50":[166],"dose":[167,280],"analyzed":[171],"post-cisplatin":[172,371],"cell-cycle":[173],"profile":[174],"over":[175],"96":[176,225,250],"hours":[177,197,219,226,290],"using":[178,208],"PI-FACS":[179],"immunoblot.":[181,209],"all":[184,284,320],"three":[185,285],"types":[187,287],"increasing":[189],"doses":[190,300],"(0-40":[191],"\u03bcM)":[192],"24":[196,289],"measured":[199],"levels":[201],"ub-PCNA":[203,273,294,413],"(K164)":[204],"Pol":[206,275,314,420,444],"\u03b7":[207,276,315,421,445],"Results":[210],"SW780-sgGFP":[211,328],"arrested":[212],"S-phase":[214,246,255,325,349,390],"at":[215,224,247,288,297,319],"48":[216,248],"72":[218],"overcame":[221],"began":[228],"again.":[231],"SW780-sg12":[232],"unable":[234],"S-phase,":[238],"whereas":[239,303],"SW780-sg109":[240,267],"able":[242],"hours.":[251],"This":[252],"pattern":[253],"further":[258,449],"confirmed":[259],"by":[260,331,411],"prolonged":[261,389],"upregulation":[262,270],"cyclin":[264],"D1":[265],"brief":[269],"SW780-sgGFP.":[272],"accumulated":[277],"responsive":[281],"manner":[282],"after":[291],"treatment.":[293],"abruptly":[296],"higher":[298],"SW780-sgGFP,":[302],"increase":[305],"gradual":[307],"CDKN1A-edited":[309],"cells.":[310],"Interestingly,":[311,375],"SW780-sg109,":[313,423],"induction":[316],"strongest":[318],"doses.":[321],"Conclusion":[322],"Cisplatin":[323],"causes":[324],"cells,":[329],"possibly":[330,424],"inducing":[332],"replicative":[333],"stress.":[334],"However,":[335],"is":[338,351,382],"eventually":[339],"bypassed":[340],"progress":[344],"through":[345],"cycle.":[348],"not":[352],"possible":[353],"absence":[356],"functioning":[359],"indicating":[361],"plays":[364],"vital":[366],"role":[367,401],"bringing":[369],"about":[370],"arrest.":[374],"truncated":[376],"intact":[379],"capable":[383],"causing":[385],"stronger":[386],"compared":[392],"full-length":[395],"may":[398],"play":[399],"tolerance":[405],"indicated":[410],"elevated":[412],"pol":[415],"\u03b7.":[416],"Stronger":[417],"accumulation":[418],"enhances":[425],"thus":[428],"resistance.":[430],"Moving":[431],"forward,":[432],"we":[433],"like":[435],"confirm":[437],"anticipated":[439],"competition":[440],"verify":[450],"phenomenon":[452],"other":[454],"cancer":[456,484],"lines.":[458],"Citation":[459],"Format:":[460],"Rahmat":[461],"K.":[462],"Sikder,":[463],"Wafik":[464],"S.":[465],"El-Deiry,":[466],"Philip":[467],"H.":[468],"Abbosh.":[469],"Differential":[470],"effects":[471],"N-terminal":[473],"vs":[474],"C-terminal":[475],"[abstract].":[485],"In:":[486],"Proceedings":[487],"American":[490],"Association":[491],"Cancer":[493,506],"Research":[494],"Annual":[495],"Meeting":[496],"2018;":[497],"2018":[498],"Apr":[499],"14-18;":[500],"Chicago,":[501],"IL.":[502],"Philadelphia":[503],"(PA):":[504],"AACR;":[505],"Res":[507],"2018;78(13":[508],"Suppl):Abstract":[509],"nr":[510],"2307.":[511]},"counts_by_year":[],"updated_date":"2026-08-21T09:56:20.448147","created_date":"2018-08-22T00:00:00"}