{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T11:06:51Z","timestamp":1785323211694,"version":"3.55.0"},"reference-count":17,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genes Chromosomes &amp; Cancer"],"published-print":{"date-parts":[[2026,7]]},"abstract":"ABSTRACT<\/jats:title>\n \n The tumor suppressor gene\n TP53<\/jats:italic>\n is a key regulator of genomic stability, frequently altered across human cancers. In hematologic malignancies,\n TP53<\/jats:italic>\n lesions\u2014typically mutations, deletions, and copy\u2010neutral loss of heterozygosity\u2014are associated with complex karyotypes, therapy resistance, and dismal prognosis. Amplifications of\n TP53<\/jats:italic>\n , however, have not been systematically described in this context. We retrospectively analyzed cases submitted to our laboratory (09\/2005\u201310\/2025) by interphase FISH in which we suspected a\n TP53<\/jats:italic>\n amplification. Among these, eight cases exhibited\n TP53<\/jats:italic>\n amplification, all classified as myeloid neoplasms (\n n<\/jats:italic>\n \u2009=\u20096 acute myeloid leukemia, AML;\n n<\/jats:italic>\n \u2009=\u20092 myelodysplastic neoplasms, MDS). Median patient age was 72\u2009years (range 48\u201383). Chromosome banding revealed highly complex karyotypes in all cases (4\u201312 aberrations), including 5q deletions (in 7\/8 patients) and \u22127\/7q\u2212 (4\/8). Targeted sequencing demonstrated concurrent\n TP53<\/jats:italic>\n mutations in all patients (median variant allele frequency 48%, range 18%\u201391%) with few additional co\u2010mutations. CNV (copy number variation) analysis confirmed focal\n TP53<\/jats:italic>\n copy number gains, but whole\u2010transcriptome sequencing showed only modest\n TP53<\/jats:italic>\n expression increases, indicating that amplification did not translate into overexpression. Clinical data available for four AML cases revealed a median overall survival of 1\u2009month. These findings indicate that\n TP53<\/jats:italic>\n amplification, although rare, constitutes a recurrent event in myeloid neoplasms, uniformly accompanied by\n TP53<\/jats:italic>\n mutation and complex cytogenetics. The combination of mutation and amplification likely confers biallelic\n TP53<\/jats:italic>\n inactivation, aligning these cases with multi\u2010hit\n TP53<\/jats:italic>\n AML\/MDS characterized by extreme genomic instability and highly adverse outcomes. Taken together, these data indicate that\n TP53<\/jats:italic>\n copy number assessment may be of potential diagnostic interest, although its role in risk stratification requires further studies.\n <\/jats:p>","DOI":"10.1002\/gcc.70154","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T10:27:53Z","timestamp":1784629673000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["\n TP53<\/i>\n <\/scp>\n Amplification, a Rare but Recurrent Alteration in Myeloid Neoplasms"],"prefix":"10.1002","volume":"65","author":[{"given":"Anna","family":"Stengel","sequence":"first","affiliation":[{"name":"MLL Munich Leukemia Laboratory Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9038-3265","authenticated-orcid":false,"given":"Manja","family":"Meggendorfer","sequence":"additional","affiliation":[{"name":"MLL Munich Leukemia Laboratory Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torsten","family":"Haferlach","sequence":"additional","affiliation":[{"name":"MLL Munich Leukemia Laboratory Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5083-9838","authenticated-orcid":false,"given":"Wencke","family":"Walter","sequence":"additional","affiliation":[{"name":"MLL Munich Leukemia Laboratory Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,21]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12634"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-018-0351-2"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2016.263"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-1008-z"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2022009100"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2021014472"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms221810105"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1080\/10428194.2020.1759051"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2008.173"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-022-01766-z"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2021006239"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-022-01613-1"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2003.08.005"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102004\u201003\u20101036"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2402329"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-02-558833"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375\u2010024\u201002297\u20105"}],"container-title":["Genes, Chromosomes and Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/gcc.70154","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/gcc.70154","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/gcc.70154","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T10:50:49Z","timestamp":1785322249000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/gcc.70154"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7]]},"references-count":17,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1002\/gcc.70154"],"URL":"https:\/\/doi.org\/10.1002\/gcc.70154","archive":["Portico"],"relation":{},"ISSN":["1045-2257","1098-2264"],"issn-type":[{"value":"1045-2257","type":"print"},{"value":"1098-2264","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7]]},"assertion":[{"value":"2026-05-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70154"}}