{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:17:00Z","timestamp":1790788620314,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,6,22]],"date-time":"2023-06-22T00:00:00Z","timestamp":1687392000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100017935","name":"Gerald O. Mann Charitable Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100017935","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018560","name":"Joseph C. Monastra Foundation for Pancreatic Cancer Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018560","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004622","name":"KWF Kankerbestrijding","doi-asserted-by":"publisher","award":["Grant 2016\u2010I 10289"],"award-info":[{"award-number":["Grant 2016\u2010I 10289"]}],"id":[{"id":"10.13039\/501100004622","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017989","name":"Rolfe Pancreatic Cancer Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100017989","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Understanding the timing and spectrum of genetic alterations that contribute to the development of pancreatic cancer is essential for effective interventions and treatments. The aim of this study was to characterize somatic <jats:italic>ATM<\/jats:italic> alterations in noninvasive pancreatic precursor lesions and invasive pancreatic adenocarcinomas from patients with and without pathogenic germline <jats:italic>ATM<\/jats:italic> variants. DNA was isolated and sequenced from the invasive pancreatic ductal adenocarcinomas and precursor lesions of patients with a pathogenic germline <jats:italic>ATM<\/jats:italic> variant. Tumor and precursor lesions from these patients as well as colloid carcinoma from patients without a germline <jats:italic>ATM<\/jats:italic> variant were immunolabeled to assess ATM expression. Among patients with a pathogenic germline <jats:italic>ATM<\/jats:italic> variant, somatic <jats:italic>ATM<\/jats:italic> alterations, either mutations and\/or loss of protein expression, were identified in 75.0% of invasive pancreatic adenocarcinomas but only 7.1% of pancreatic precursor lesions. Loss of ATM expression was also detected in 31.0% of colloid carcinomas from patients unselected for germline <jats:italic>ATM<\/jats:italic> status, significantly higher than in pancreatic precursor lesions [pancreatic intraepithelial neoplasms (<jats:italic>p<\/jats:italic>\u2009=\u20090.0013); intraductal papillary mucinous neoplasms, <jats:italic>p<\/jats:italic>\u2009=\u20090.0040] and pancreatic ductal adenocarcinoma (<jats:italic>p<\/jats:italic>\u2009=\u20090.0076) unselected for germline ATM status. These data are consistent with the second hit to <jats:italic>ATM<\/jats:italic> being a late event in pancreatic tumorigenesis. \u00a9 2023 The Authors. <jats:italic>The Journal of Pathology<\/jats:italic> published by John Wiley &amp; Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.<\/jats:p>","DOI":"10.1002\/path.6136","type":"journal-article","created":{"date-parts":[[2023,6,24]],"date-time":"2023-06-24T14:40:04Z","timestamp":1687617604000},"page":"455-464","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Somatic loss of <i>ATM<\/i> is a late event in pancreatic tumorigenesis"],"prefix":"10.1002","volume":"260","author":[{"given":"Raymond M","family":"Paranal","sequence":"first","affiliation":[{"name":"Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center The Johns Hopkins University School of Medicine  Baltimore MD USA"},{"name":"Human Genetics Predoctoral Training Program, The McKusick\u2010Nathans Department of Genetic Medicine The Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengdong","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center The Johns Hopkins University School of Medicine  Baltimore MD USA"},{"name":"Department of General Surgery The First Affiliated Hospital of Xi'an Jiaotong University  Xi'an PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle","family":"Hutchings","sequence":"additional","affiliation":[{"name":"Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center The Johns Hopkins University School of Medicine  Baltimore MD USA"},{"name":"Department of Pathology and Laboratory Medicine Cedars\u2010Sinai Medical Center  Los Angeles CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1020-6606","authenticated-orcid":false,"given":"Valentyna","family":"Kryklyva","sequence":"additional","affiliation":[{"name":"Department of Pathology Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Gauthier","sequence":"additional","affiliation":[{"name":"Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center The Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohei","family":"Fujikura","sequence":"additional","affiliation":[{"name":"Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center The Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neha","family":"Nanda","sequence":"additional","affiliation":[{"name":"Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center The Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center The Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4960-875X","authenticated-orcid":false,"given":"Michael","family":"Skaro","sequence":"additional","affiliation":[{"name":"Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center The Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher L","family":"Wolfgang","sequence":"additional","affiliation":[{"name":"Department of Surgery NYU Grossman School of Medicine  New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"He","sequence":"additional","affiliation":[{"name":"Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center The Johns Hopkins University School of Medicine  Baltimore MD USA"},{"name":"Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center The Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David S","family":"Klimstra","sequence":"additional","affiliation":[{"name":"Department of Pathology Memorial Sloan Kettering Cancer Center  New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randall E","family":"Brand","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Pittsburgh Medical Center  Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3930-7096","authenticated-orcid":false,"given":"Aatur D","family":"Singhi","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Pittsburgh Medical Center  Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo","family":"DeMarzo","sequence":"additional","affiliation":[{"name":"Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center The Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center The Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4286-2296","authenticated-orcid":false,"given":"Michael","family":"Goggins","sequence":"additional","affiliation":[{"name":"Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center The Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lodewijk AA","family":"Brosens","sequence":"additional","affiliation":[{"name":"Department of Pathology Radboud University Medical Center  Nijmegen The Netherlands"},{"name":"Department of Pathology University Medical Center  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4554-5672","authenticated-orcid":false,"given":"Ralph H","family":"Hruban","sequence":"additional","affiliation":[{"name":"Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center The Johns Hopkins University School of Medicine  Baltimore MD USA"},{"name":"Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center The Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison P","family":"Klein","sequence":"additional","affiliation":[{"name":"Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center The Johns Hopkins University School of Medicine  Baltimore MD USA"},{"name":"Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center The Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0494-9067","authenticated-orcid":false,"given":"Tamara","family":"Lotan","sequence":"additional","affiliation":[{"name":"Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center The Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura D","family":"Wood","sequence":"additional","affiliation":[{"name":"Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center The Johns Hopkins University School of Medicine  Baltimore MD USA"},{"name":"Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center The Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8709-0664","authenticated-orcid":false,"given":"Nicholas J","family":"Roberts","sequence":"additional","affiliation":[{"name":"Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center The Johns Hopkins University School of Medicine  Baltimore MD USA"},{"name":"Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center The Johns Hopkins University School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,6,22]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21654"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.72.3502"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-018-0009-5"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2018.6228"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2021.0017"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.18.01489"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2012-303108"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2014.435"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2004.03.011"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.22528"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2019.01.254"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-11-0194"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.12490"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-15-0402"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2017.85"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2017.07.007"},{"key":"e_1_2_8_18_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1200\/PO.17.00098","article-title":"Reflex testing for germline BRCA1, BRCA2, PALB2, and ATM mutations in pancreatic cancer: mutation prevalence and clinical outcomes from two Canadian research registries","volume":"2","author":"Smith AL","year":"2018","journal-title":"JCO Precis Oncol"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2021.3701"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.31218"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-10-0893"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aan6733"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-019-0317-6"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-19-3126"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-020-1016-2"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-17-0634"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2019-319970"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9092110"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-22-1483"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms8677"},{"key":"e_1_2_8_31_1","first-page":"417","volume-title":"WHO Classification of Tumours of the Digestive System","author":"Bosman FT","year":"2010"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000000533"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.4884"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp698"},{"key":"e_1_2_8_35_1","article-title":"Calling somatic SNVs and indels with Mutect2","author":"Benjamin D","year":"2019","journal-title":"bioRxiv"},{"key":"e_1_2_8_36_1","article-title":"Scaling accurate genetic variant discovery to tens of thousands of samples","author":"Poplin R","year":"2018","journal-title":"bioRxiv"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq603"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-17-0337"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-20-0764"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-13-1239"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.68.4.820"}],"container-title":["The Journal of Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/path.6136","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T10:02:16Z","timestamp":1761040936000},"score":1,"resource":{"primary":{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/10.1002\/path.6136"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,22]]},"references-count":40,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2023,8]]}},"alternative-id":["10.1002\/path.6136"],"URL":"https:\/\/doi.org\/10.1002\/path.6136","archive":["Portico"],"relation":{},"ISSN":["0022-3417","1096-9896"],"issn-type":[{"value":"0022-3417","type":"print"},{"value":"1096-9896","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,22]]},"assertion":[{"value":"2023-01-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-05-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-06-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}