ArticleMolecular medicine (Cambridge, Mass.)2026
Prevalence of heterozygous and homozygous 9p21 deletions in human cancer: a tissue microarray study on 4,999 tumors from 125 different tumor types.
Article in Molecular medicine (Cambridge, Mass.), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundHomozygous 9p21 deletions are the major cause for MTAP deficiency, making cancer cells more vulnerable towards drugs targeting various pathways. This study aimed to assess the prevalence of heterozygous and homozygous 9p21 deletions in cancer.
methodsA tissue microarray containing 7,172 samples from 125 different tumor entities was analyzed by fluorescence in situ hybridization. This method allows the detection of deletions within single tumor cells, while admixted non-neoplastic cells are omitted. Consecutive sections were immunostained for MTAP and p16 (CDKN2A).
resultsAmong 4,999 evaluable tumors, 10.7% had heterozygous and 7.4% homozygous deletions, which occurred in different tumor categories. Homozygous deletions were most frequent in mesothelioma (up to 47.8%), pancreatic ductal adenocarcinoma (44.7%), and urothelial carcinoma (up to 36.4%) while heterozygous deletions predominated in squamous cell carcinoma (up to 34.3%), leiomyosarcoma (31.4%), and esophageal adenocarcinoma (30.8%). The proportion of homozygous 9p21 deletions was high in mesothelioma (up to 91.6%), urothelial carcinoma (up to 80.0%), and pancreatic ductal adenocarcinoma (76.4%), intermediate in squamous cell carcinomas of different organs (12.5-50.0%) and pulmonary adenocarcinoma (46.3%), and low in endometrioid (9.1%) and high-grade serous (4.0%) ovarian carcinoma. MTAP and p16 immunostaining was absent in homozygous 9p21 deletions, while heterozygously deleted cancers showed markedly decreased MTAP immunostaining (p < 0.0001), with unchanged p16 staining.
conclusionsThese data provide a comprehensive overview on the prevalence on homozygous and heterozygous 9p21 deletions in cancer and demonstrate that different cancer types markedly differ in their ratio of homozygous/heterozygous 9p21 deletions. The strong concordance between homozygous 9p21 deletions and absent MTAP immunostaining highlights the effectiveness of immunohistochemistry in detecting MTAP deficiency.
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