{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T06:38:55Z","timestamp":1792219135151,"version":"4.4.0"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2024,2,8]],"date-time":"2024-02-08T00:00:00Z","timestamp":1707350400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,6,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>One of the most common sporadic homozygous deletions in cancers is 9p21 loss, which includes the genes methylthioadenosine phosphorylase (MTAP), CDKN2A, and CDKN2B, and has been correlated with worsened outcomes and immunotherapy resistance. MTAP-loss is a developing drug target through synthetic lethality with MAT2A and PMRT5 inhibitors. The purpose of this study is to investigate the prevalence and genomic landscape of MTAP-loss in advanced gastrointestinal (GI) tumors and investigate its role as a prognostic biomarker.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>We performed next-generation sequencing and comparative genomic and clinical analysis on an extensive cohort of 64 860 tumors comprising 5 GI cancers. We compared the clinical outcomes of patients with GI cancer harboring MTAP-loss and MTAP-intact tumors in a retrospective study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The prevalence of MTAP-loss in GI cancers is 8.30%. MTAP-loss was most prevalent in pancreatic ductal adenocarcinoma (PDAC) at 21.7% and least in colorectal carcinoma (CRC) at 1.1%. MTAP-loss tumors were more prevalent in East Asian patients with PDAC (4.4% vs 3.2%, P\u2005=\u2005.005) or intrahepatic cholangiocarcinoma (IHCC; 6.4% vs 4.3%, P\u2005=\u2005.036). Significant differences in the prevalence of potentially targetable genomic alterations (ATM, BRAF, BRCA2, ERBB2, IDH1, PIK3CA, and PTEN) were observed in MTAP-loss tumors and varied according to tumor type. MTAP-loss PDAC, IHCC, and CRC had a lower prevalence of microsatellite instability or elevated tumor mutational burden. Positive PD-L1 tumor cell expression was less frequent among MTAP-loss versus MTAP-intact IHCC tumors (23.2% vs 31.2%, P\u2005=\u2005.017).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In GI cancers, MTAP-loss occurs as part of 9p21 loss and has an overall prevalence of 8%. MTAP-loss occurs in 22% of PDAC, 15% of IHCC, 8.7% of gastroesophageal adenocarcinoma, 2.4% of hepatocellular carcinoma, and 1.1% of CRC and is not mutually exclusive with other targetable mutations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/oncolo\/oyae011","type":"journal-article","created":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T00:11:31Z","timestamp":1706746291000},"page":"493-503","source":"Crossref","is-referenced-by-count":42,"title":["Methylthioadenosine Phosphorylase Genomic Loss in Advanced Gastrointestinal Cancers"],"prefix":"10.1093","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2071-0715","authenticated-orcid":false,"given":"Natalie Y L","family":"Ngoi","sequence":"first","affiliation":[{"name":"Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center , Houston, TX , USA"},{"name":"Department of Haematology-Oncology, National University Cancer Institute , Singapore , Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2030-9518","authenticated-orcid":false,"given":"Tin-Yun","family":"Tang","sequence":"additional","affiliation":[{"name":"Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center , Houston, TX , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catia F","family":"Gaspar","sequence":"additional","affiliation":[{"name":"Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center , Houston, TX , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6075-6246","authenticated-orcid":false,"given":"Dean C","family":"Pavlick","sequence":"additional","affiliation":[{"name":"Foundation Medicine Inc. , Cambridge, MA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory M","family":"Buchold","sequence":"additional","affiliation":[{"name":"Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center , Houston, TX , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma L","family":"Scholefield","sequence":"additional","affiliation":[{"name":"Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde Glasgow , Glasgow , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vamsi","family":"Parimi","sequence":"additional","affiliation":[{"name":"Foundation Medicine Inc. , Cambridge, MA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard S P","family":"Huang","sequence":"additional","affiliation":[{"name":"Foundation Medicine Inc. , Cambridge, MA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyler","family":"Janovitz","sequence":"additional","affiliation":[{"name":"Foundation Medicine Inc. , Cambridge, MA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Danziger","sequence":"additional","affiliation":[{"name":"Foundation Medicine Inc. , Cambridge, MA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mia A","family":"Levy","sequence":"additional","affiliation":[{"name":"Foundation Medicine Inc. , Cambridge, MA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shubham","family":"Pant","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center , Houston, TX , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9614-8867","authenticated-orcid":false,"given":"Anaemy Danner","family":"De Armas","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center , Houston, TX , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Kumpula","sequence":"additional","affiliation":[{"name":"Departments of Pathology, Urology and Medicine (Oncology), Upstate Medical University , Syracuse, NY , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8494-2596","authenticated-orcid":false,"given":"Jeffrey S","family":"Ross","sequence":"additional","affiliation":[{"name":"Foundation Medicine Inc. , Cambridge, MA , USA"},{"name":"Departments of Pathology, Urology and Medicine (Oncology), Upstate Medical University , Syracuse, NY , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9158-0941","authenticated-orcid":false,"given":"Milind","family":"Javle","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center , Houston, TX , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6467-3632","authenticated-orcid":false,"given":"Jordi","family":"Rodon Ahnert","sequence":"additional","affiliation":[{"name":"Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center , Houston, TX , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,2,8]]},"reference":[{"key":"2024060305573468800_CIT0001","first-page":"1221","article-title":"Pan-cancer analysis of homozygous deletions in primary tumours uncovers rare tumour suppressors","volume-title":"Nat Commun.","author":"Cheng","year":"2017"},{"key":"2024060305573468800_CIT0002","first-page":"4542","article-title":"A survey of homozygous deletions in human cancer genomes","volume-title":"Proc Natl Acad Sci 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