{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:08:03Z","timestamp":1791288483656,"version":"4.3.0"},"reference-count":41,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: The complete loss of S-methyl-5\u2032-thioadenosine phosphorylase (MTAP) expression, often due to homozygous 9p21 deletion, creates a druggable vulnerability in cancer cells. Methods: A total of 769 primary pancreatic ductal adenocarcinomas were analyzed on tissue microarrays with MTAP immunohistochemistry (IHC) and 9p21 fluorescence in situ hybridization (FISH). Intratumoral heterogeneity was assessed on a \u201cheterogeneity\u201d TMA containing up to nine samples from different areas of 236 primary tumor and nodal metastases, and whole sections of all tumor blocks from 19 cancers. Results: MTAP expression loss was found in 181 (37.9%) of 478 interpretable primary tumors and was unrelated to pT, pN, grade, and tumor size. MTAP expression loss was homogenous in 37.6% and heterogeneous in 1.1% of the 181 tumors, with at least three evaluable samples on the heterogeneity TMA. On whole sections, 1 of 19 tumors showed heterogeneous MTAP loss. The correlation between IHC and FISH was nearly perfect, with 98.8% of MTAP-deficient samples showing a 9p21 deletion. Conclusions: MTAP expression loss is frequent, caused by homozygous deletion, and mostly homogeneous in pancreatic ductal adenocarcinomas. Considering also their aggressive clinical behavior, pancreatic adenocarcinomas may represent an ideal cancer type for studying new drugs targeting MTAP-deficient cancer cells in clinical trials.<\/jats:p>","DOI":"10.3390\/cancers17071205","type":"journal-article","created":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T04:06:05Z","timestamp":1743566765000},"page":"1205","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Deficiency of MTAP Is Frequent and Mostly Homogeneous in Pancreatic Ductal Adenocarcinomas"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-6680-8788","authenticated-orcid":false,"given":"Natalia","family":"Gorbokon","sequence":"first","affiliation":[{"name":"Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Teljuk","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktor","family":"Reiswich","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1572-8200","authenticated-orcid":false,"given":"Maximilian","family":"Lennartz","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Minner","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0158-4258","authenticated-orcid":false,"given":"Ronald","family":"Simon","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9024-4978","authenticated-orcid":false,"given":"Guido","family":"Sauter","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waldemar","family":"Wilczak","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4257-856X","authenticated-orcid":false,"given":"Till Sebastian","family":"Clauditz","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3056-2974","authenticated-orcid":false,"given":"Nina","family":"Schraps","sequence":"additional","affiliation":[{"name":"General, Visceral and Thoracic Surgery Department and Clinic, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thilo","family":"Hackert","sequence":"additional","affiliation":[{"name":"General, Visceral and Thoracic Surgery Department and Clinic, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6890-4829","authenticated-orcid":false,"given":"Faik G.","family":"Uzunoglu","sequence":"additional","affiliation":[{"name":"General, Visceral and Thoracic Surgery Department and Clinic, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Kluth","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5970-1803","authenticated-orcid":false,"given":"Lukas","family":"Bubendorf","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University Hospital Basel, 4031 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Matter","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University Hospital Basel, 4031 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Viehweger","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3841-444X","authenticated-orcid":false,"given":"Morton","family":"Freytag","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Jacobsen","sequence":"additional","affiliation":[{"name":"Pathologie-Hamburg, Labor Lademannbogen MVZ GmbH, 22419 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"M\u00f6ller","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Steurer","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"12324","DOI":"10.1016\/S0021-9258(18)67242-4","article-title":"Purification and characterization of 5\u2032-deoxy-5\u2032-methylthioadenosine phosphorylase from human placenta","volume":"261","author":"Gragnaniello","year":"1986","journal-title":"J. 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