{"id":"https://openalex.org/W27728188","doi":"https://doi.org/10.1016/s0002-9440(10)65047-x","title":"BRCA2 Is Inactivated Late in the Development of Pancreatic Intraepithelial Neoplasia","display_name":"BRCA2 Is Inactivated Late in the Development of Pancreatic Intraepithelial Neoplasia","publication_year":2000,"publication_date":"2000-05-01","ids":{"openalex":"https://openalex.org/W27728188","doi":"https://doi.org/10.1016/s0002-9440(10)65047-x","mag":"27728188","pmid":"https://pubmed.ncbi.nlm.nih.gov/10793087","pmcid":"https://www.ncbi.nlm.nih.gov/pmc/articles/1876938"},"language":"en","primary_location":{"id":"doi:10.1016/s0002-9440(10)65047-x","doi":"https://doi.org/10.1016/s0002-9440(10)65047-x","is_oa":true,"landing_page_url":"https://doi.org/10.1016/s0002-9440(10)65047-x","pdf_url":"http://ajp.amjpathol.org/article/S000294401065047X/pdf","source":{"id":"https://openalex.org/S145577119","display_name":"American Journal Of Pathology","issn_l":"0002-9440","issn":["0002-9440","1525-2191"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-b","doyens","jufo-2","ki-jl-2","medline","norway-2","poland-140","russia-white-list-1"],"host_organization":"https://openalex.org/P4310320990","host_organization_name":"Elsevier BV","host_organization_lineage":["https://openalex.org/P4310320990"],"host_organization_lineage_names":["Elsevier BV"],"type":"journal"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"The American Journal of Pathology","raw_type":"journal-article"},"volume":null,"type":"article","indexed_in":["crossref","pubmed"],"open_access":{"is_oa":true,"oa_status":"hybrid","oa_url":"http://ajp.amjpathol.org/article/S000294401065047X/pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5090286753","display_name":"Michael Goggins","orcid":"https://orcid.org/0000-0002-4286-2296","observed_orcids":["https://orcid.org/0000-0002-4286-2296"]},"institutions":[{"id":"https://openalex.org/I145311948","display_name":"Johns Hopkins University","ror":"https://ror.org/00za53h95","country_code":"US","type":"education","lineage":["https://openalex.org/I145311948"]},{"id":"https://openalex.org/I2799853436","display_name":"Johns Hopkins Medicine","ror":"https://ror.org/037zgn354","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I2799853436"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Michael Goggins","raw_affiliation_strings":["Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205-2196, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205-2196, USA","institution_ids":["https://openalex.org/I145311948","https://openalex.org/I2799853436"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5001682484","display_name":"Ralph H. Hruban","orcid":"https://orcid.org/0000-0003-4554-5672","observed_orcids":["https://orcid.org/0000-0003-4554-5672"]},"institutions":[{"id":"https://openalex.org/I145311948","display_name":"Johns Hopkins University","ror":"https://ror.org/00za53h95","country_code":"US","type":"education","lineage":["https://openalex.org/I145311948"]},{"id":"https://openalex.org/I2799853436","display_name":"Johns Hopkins Medicine","ror":"https://ror.org/037zgn354","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I2799853436"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Ralph H. Hruban","raw_affiliation_strings":["Departments of Pathology and Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Departments of Pathology and Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland","institution_ids":["https://openalex.org/I145311948","https://openalex.org/I2799853436"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5108816594","display_name":"Scott E. Kern","orcid":"https://orcid.org/0009-0000-3645-4889","observed_orcids":["https://orcid.org/0009-0000-3645-4889"]},"institutions":[{"id":"https://openalex.org/I145311948","display_name":"Johns Hopkins University","ror":"https://ror.org/00za53h95","country_code":"US","type":"education","lineage":["https://openalex.org/I145311948"]},{"id":"https://openalex.org/I2799853436","display_name":"Johns Hopkins Medicine","ror":"https://ror.org/037zgn354","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I2799853436"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Scott E. Kern","raw_affiliation_strings":["Departments of Pathology and Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Departments of Pathology and Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland","institution_ids":["https://openalex.org/I145311948","https://openalex.org/I2799853436"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":["https://openalex.org/A5108816594"],"corresponding_institution_ids":["https://openalex.org/I145311948","https://openalex.org/I2799853436"],"apc_list":{"value":2800,"currency":"USD","value_usd":2800},"apc_paid":{"value":2800,"currency":"USD","value_usd":2800},"fwci":7.1928,"has_fulltext":true,"cited_by_count":212,"citation_normalized_percentile":{"value":0.97706547,"is_in_top_1_percent":false,"is_in_top_10_percent":true},"cited_by_percentile_year":{"min":89,"max":99},"biblio":{"volume":"156","issue":"5","first_page":"1767","last_page":"1771"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10231","display_name":"Pancreatic and Hepatic Oncology Research","score":0.9643999934196472,"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"}},"topics":[{"id":"https://openalex.org/T10231","display_name":"Pancreatic and Hepatic Oncology Research","score":0.9643999934196472,"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/T10769","display_name":"BRCA gene mutations in cancer","score":0.02810000069439411,"subfield":{"id":"https://openalex.org/subfields/1311","display_name":"Genetics"},"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/T11369","display_name":"Genetic factors in colorectal cancer","score":0.0026000000070780516,"subfield":{"id":"https://openalex.org/subfields/2734","display_name":"Pathology and Forensic Medicine"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/brca2","display_name":"BRCA2","score":0.9940000176429749},{"id":"https://openalex.org/keywords/pancreatic-intraepithelial-neoplasia","display_name":"pancreatic intraepithelial neoplasia","score":0.9610000252723694},{"id":"https://openalex.org/keywords/biallelic-inactivation","display_name":"biallelic inactivation","score":0.871999979019165},{"id":"https://openalex.org/keywords/loss-of-heterozygosity","display_name":"loss of heterozygosity","score":0.8899999856948853},{"id":"https://openalex.org/keywords/pancreatic-ductal-adenocarcinoma","display_name":"pancreatic ductal adenocarcinoma","score":0.9559999704360962},{"id":"https://openalex.org/keywords/germline-brca2-mutation","display_name":"germline BRCA2 mutation","score":0.8429999947547913},{"id":"https://openalex.org/keywords/kras-mutation","display_name":"KRAS mutation","score":0.7760000228881836},{"id":"https://openalex.org/keywords/pancreatic-carcinogenesis","display_name":"pancreatic carcinogenesis","score":0.9100000262260437},{"id":"https://openalex.org/keywords/precancerous-lesions","display_name":"precancerous lesions","score":0.5860000252723694},{"id":"https://openalex.org/keywords/penetrance","display_name":"penetrance","score":0.4880000054836273},{"id":"https://openalex.org/keywords/age-of-onset","display_name":"age of onset","score":0.9010000228881836}],"concepts":[{"id":"https://openalex.org/C2909925829","wikidata":"https://www.wikidata.org/wiki/Q212961","display_name":"Pancreatic Intraepithelial Neoplasia","level":5,"score":0.6196346879005432},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.47936373949050903},{"id":"https://openalex.org/C142724271","wikidata":"https://www.wikidata.org/wiki/Q7208","display_name":"Pathology","level":1,"score":0.4108675420284271},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.359149694442749},{"id":"https://openalex.org/C2780210213","wikidata":"https://www.wikidata.org/wiki/Q212961","display_name":"Pancreatic cancer","level":3,"score":0.2722293436527252},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.21874123811721802},{"id":"https://openalex.org/C2992026798","wikidata":"https://www.wikidata.org/wiki/Q212961","display_name":"Pancreatic ductal adenocarcinoma","level":4,"score":0.1814553439617157},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.17156541347503662}],"mesh":[{"descriptor_ui":"D002278","descriptor_name":"Carcinoma in Situ","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D002278","descriptor_name":"Carcinoma in Situ","qualifier_ui":"Q000473","qualifier_name":"pathology","is_major_topic":false},{"descriptor_ui":"D004252","descriptor_name":"DNA Mutational Analysis","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D004273","descriptor_name":"DNA, Neoplasm","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":false},{"descriptor_ui":"D004273","descriptor_name":"DNA, Neoplasm","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D009154","descriptor_name":"Mutation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D009363","descriptor_name":"Neoplasm Proteins","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D010190","descriptor_name":"Pancreatic Neoplasms","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D010190","descriptor_name":"Pancreatic Neoplasms","qualifier_ui":"Q000473","qualifier_name":"pathology","is_major_topic":false},{"descriptor_ui":"D011905","descriptor_name":"Genes, ras","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":false},{"descriptor_ui":"D014157","descriptor_name":"Transcription Factors","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D019656","descriptor_name":"Loss of Heterozygosity","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D024682","descriptor_name":"BRCA2 Protein","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":3,"locations":[{"id":"doi:10.1016/s0002-9440(10)65047-x","doi":"https://doi.org/10.1016/s0002-9440(10)65047-x","is_oa":true,"landing_page_url":"https://doi.org/10.1016/s0002-9440(10)65047-x","pdf_url":"http://ajp.amjpathol.org/article/S000294401065047X/pdf","source":{"id":"https://openalex.org/S145577119","display_name":"American Journal Of Pathology","issn_l":"0002-9440","issn":["0002-9440","1525-2191"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-b","doyens","jufo-2","ki-jl-2","medline","norway-2","poland-140","russia-white-list-1"],"host_organization":"https://openalex.org/P4310320990","host_organization_name":"Elsevier BV","host_organization_lineage":["https://openalex.org/P4310320990"],"host_organization_lineage_names":["Elsevier BV"],"type":"journal"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"The American Journal of Pathology","raw_type":"journal-article"},{"id":"pmh:oai:pubmedcentral.nih.gov:1876938","doi":null,"is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/1876938","pdf_url":null,"source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Am J Pathol","raw_type":"Text"},{"id":"pmid:10793087","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/10793087","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"The American journal of pathology","raw_type":"Journal Article"}],"best_oa_location":{"id":"doi:10.1016/s0002-9440(10)65047-x","doi":"https://doi.org/10.1016/s0002-9440(10)65047-x","is_oa":true,"landing_page_url":"https://doi.org/10.1016/s0002-9440(10)65047-x","pdf_url":"http://ajp.amjpathol.org/article/S000294401065047X/pdf","source":{"id":"https://openalex.org/S145577119","display_name":"American Journal Of Pathology","issn_l":"0002-9440","issn":["0002-9440","1525-2191"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-b","doyens","jufo-2","ki-jl-2","medline","norway-2","poland-140","russia-white-list-1"],"host_organization":"https://openalex.org/P4310320990","host_organization_name":"Elsevier BV","host_organization_lineage":["https://openalex.org/P4310320990"],"host_organization_lineage_names":["Elsevier BV"],"type":"journal"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"The American Journal of Pathology","raw_type":"journal-article"},"sustainable_development_goals":[{"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3","score":0.98580002784729}],"study_designs":[],"awards":[{"id":"https://openalex.org/G8373782936","display_name":"SPORE in Gastrointestinal Cancers","funder_award_id":"P50CA062924","funder_id":"https://openalex.org/F4320337351","funder_display_name":"National Cancer Institute"},{"id":"https://openalex.org/G970037175","display_name":null,"funder_award_id":"CA 62924","funder_id":"https://openalex.org/F4320337351","funder_display_name":"National Cancer Institute"}],"funders":[{"id":"https://openalex.org/F4320332161","display_name":"National Institutes of Health","ror":"https://ror.org/01cwqze88"},{"id":"https://openalex.org/F4320337351","display_name":"National Cancer Institute","ror":"https://ror.org/040gcmg81"}],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W27728188.pdf","grobid_xml":"https://content.openalex.org/works/W27728188.grobid-xml"},"referenced_works_count":39,"referenced_works":["https://openalex.org/W62932861","https://openalex.org/W149099508","https://openalex.org/W156926268","https://openalex.org/W1506859968","https://openalex.org/W1507944948","https://openalex.org/W1604056813","https://openalex.org/W1762220600","https://openalex.org/W1785779992","https://openalex.org/W2009759387","https://openalex.org/W2016634986","https://openalex.org/W2018299474","https://openalex.org/W2018510608","https://openalex.org/W2021851245","https://openalex.org/W2024986660","https://openalex.org/W2038437309","https://openalex.org/W2055294712","https://openalex.org/W2058218248","https://openalex.org/W2072751885","https://openalex.org/W2086109625","https://openalex.org/W2091723114","https://openalex.org/W2096010941","https://openalex.org/W2097358179","https://openalex.org/W2112187879","https://openalex.org/W2120724429","https://openalex.org/W2145903120","https://openalex.org/W2153926167","https://openalex.org/W2157330585","https://openalex.org/W2171148836","https://openalex.org/W2207620686","https://openalex.org/W2285254054","https://openalex.org/W2403010325","https://openalex.org/W2404126400","https://openalex.org/W2404160391","https://openalex.org/W2415952861","https://openalex.org/W2416513008","https://openalex.org/W6636179402","https://openalex.org/W6638290384","https://openalex.org/W6683387562","https://openalex.org/W6713386444"],"related_works":["https://openalex.org/W2039479626","https://openalex.org/W2085770388","https://openalex.org/W2129234664","https://openalex.org/W1785779992","https://openalex.org/W2019547074","https://openalex.org/W2011982648","https://openalex.org/W2590096567","https://openalex.org/W2081681778","https://openalex.org/W2040252009","https://openalex.org/W1991963191"],"abstract_inverted_index":{"Patients":[0],"harboring":[1],"germline":[2,43,103],"BRCA2":[3,22,44,77,104,142,180,246],"mutations":[4,45,163],"are":[5],"at":[6,75,97,111],"an":[7],"increased":[8],"risk":[9],"of":[10,18,21,73,91,101,120,127,137,141,154,168,178,197,201,208,226,238,255,267,269],"developing":[11],"pancreatic":[12,29,32,48,188,270],"cancer.":[13,228],"We":[14],"investigated":[15],"the":[16,24,76,92,98,102,118,125,138,169,179,199,202,218,223],"prevalence":[17,126],"biallelic":[19,176,236],"inactivation":[20,177,200,237],"in":[23,129,145,152,166,187,205],"presumed":[25],"precursors":[26],"to":[27,116,192],"invasive":[28],"ductal":[30,49],"carcinomas,":[31],"intraepithelial":[33],"neoplasia":[34],"(PanIN).":[35],"Surgical":[36],"resection":[37],"specimens":[38],"from":[39,57,63],"three":[40],"patients":[41,131],"with":[42],"who":[46],"developed":[47],"adenocarcinoma":[50],"were":[51,55,164],"studied.":[52],"Fourteen":[53],"PanINs":[54,128,157],"needle-microdissected":[56],"paraffin-embedded":[58],"tissue.":[59],"DNA":[60],"was":[61,79,95,109,132,143],"isolated":[62],"these":[64,130],"microdissected":[65],"tissues":[66],"and":[67,86,114,264,271],"amplified":[68],"by":[69,81],"primer-mediated":[70],"pre-amplification.":[71],"Loss":[72,136],"heterozygosity":[74],"locus":[78],"determined":[80],"polymerase":[82],"chain":[83],"reaction":[84],"amplification":[85],"cycle":[87],"sequencing.":[88],"The":[89,106,229],"presence":[90],"wild-type":[93,139,203],"alleles":[94],"evaluated":[96],"nucleotide":[99],"positions":[100],"mutations.":[105],"K-ras":[107,162],"gene":[108,181,213,243],"sequenced":[110],"codon":[112],"12":[113],"13":[115,155],"confirm":[117],"efficacy":[119],"microdissection.":[121],"By":[122],"histological":[123],"evaluation":[124],"not":[133,215],"notably":[134],"elevated.":[135],"allele":[140,204],"present":[144],"one":[146],"high-grade":[147],"PanIN":[148],"(PanIN":[149,158],"3),":[150],"but":[151],"none":[153],"low-grade":[156],"1).":[159],"In":[160,190],"contrast,":[161],"detectable":[165],"7":[167],"14":[170],"PanINs.":[171],"These":[172],"results":[173],"suggest":[174],"that":[175],"is":[182],"a":[183,206,209,227,239,259],"relatively":[184,260],"late":[185,265],"event":[186,221],"tumorigenesis.":[189],"contrast":[191],"classical":[193],"molecular":[194,224],"progression":[195],"models":[196],"tumorigenesis,":[198],"carrier":[207],"recessive":[210,240],"tumor":[211,241],"susceptibility":[212,242],"may":[214,247],"always":[216],"be":[217],"first":[219],"somatic":[220],"during":[222],"evolution":[225],"necessity":[230],"for":[231],"earlier":[232],"genetic":[233],"alterations":[234],"before":[235],"such":[244],"as":[245],"explain":[248],"why":[249],"affected":[250],"carriers":[251],"have":[252],"normal":[253],"numbers":[254],"neoplastic":[256],"precursor":[257],"lesions,":[258],"low":[261],"phenotypic":[262],"penetrance,":[263],"age":[266],"onset":[268],"other":[272],"cancers.":[273]},"counts_by_year":[{"year":2024,"cited_by_count":4},{"year":2023,"cited_by_count":5},{"year":2022,"cited_by_count":1},{"year":2021,"cited_by_count":3},{"year":2020,"cited_by_count":2},{"year":2019,"cited_by_count":5},{"year":2018,"cited_by_count":3},{"year":2017,"cited_by_count":8},{"year":2016,"cited_by_count":5},{"year":2015,"cited_by_count":6},{"year":2014,"cited_by_count":8},{"year":2013,"cited_by_count":5},{"year":2012,"cited_by_count":7}],"updated_date":"2026-10-31T12:09:11.096373","created_date":"2016-06-24T00:00:00"}