{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:20:17Z","timestamp":1784557217332,"version":"3.55.0"},"reference-count":0,"publisher":"Bioscientifica","content-domain":{"domain":["erc.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:p>Children diagnosed with adrenocortical tumors (pACT) have variable outcomes and, to date, the disease lacks robust prognostic biomarkers. The prognostic potential of tumor methylation has been demonstrated in several cancers. We aimed to evaluate the pACT methylation profile and its association with disease presentation and survival. In this cross-sectional study, we accessed the DNA methylation (MethylationEPIC Array, Illumina) of 57 primary pACT from Southeastern Brazil and the respective patients\u2019 clinicopathological features. We also applied our analysis in an independent 48 pACT methylation data-set. Unsupervised learning whole-methylome analysis showed two groups with distinct methylation signatures: pACT-1 and pACT-2. Compared to pACT-2, pACT-1 tumors were enriched for higher methylation in CpG islands, mainly in gene promoter regions. The top-most hypermethylated gene in these samples was shown to be under-expressed. Patients in the pACT-1 group were older at diagnosis and were more likely to have carcinomas, non-localized\/advanced and recurrent\/metastatic disease. Univariate and bivariate regressions showed that pACT-1 methylation signature confers superior hazard-ratio of disease progression and death than known prognostic features. The methylation groups had similar frequencies of germline mutations in the TP53 gene, including the regionally frequent p.R337H. Our analysis replication validated our findings and reproduced those recently described in pACT. Conclusions: We demonstrated the existence of different tumor methylation signatures associated with pACT presentation and clinical evolution, even in the context of germline TP53 mutations. Our data support tumor methylation profiling as a robust and independent prognostic biomarker for pACT and suggest a list of candidate genes for further validation.<\/jats:p>","DOI":"10.1530\/erc-22-0145","type":"journal-article","created":{"date-parts":[[2022,8,30]],"date-time":"2022-08-30T11:53:39Z","timestamp":1661860419000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-8","source":"Crossref","is-referenced-by-count":4,"title":["DNA methylation is a comprehensive marker for pediatric adrenocortical tumors"],"prefix":"10.1530","author":[{"given":"Ana Carolina","family":"Bueno","sequence":"first","affiliation":[{"name":"A Bueno, Pediatrics, Universidade de Sao Paulo Faculdade de Medicina de Ribeirao Preto, Ribeirao Preto, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui M. P.","family":"da Silva","sequence":"additional","affiliation":[{"name":"R da Silva, Internal Medicine Ribeirao Preto Medical School, Universidade de Sao Paulo Faculdade de Medicina de Ribeirao Preto, Ribeirao Preto, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00f4nica F.","family":"Stecchini","sequence":"additional","affiliation":[{"name":"M Stecchini, Pediatrics, Universidade de Sao Paulo Faculdade de Medicina de Ribeirao Preto, Ribeirao Preto, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junier","family":"Marrero-Guti\u00e9rrez","sequence":"additional","affiliation":[{"name":"J Marrero-Guti\u00e9rrez, Pediatrics, Universidade de Sao Paulo Faculdade de Medicina de Ribeirao Preto, Ribeirao Preto, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danillo C.","family":"de Almeida e Silva","sequence":"additional","affiliation":[{"name":"D de Almeida e Silva, Internal Medicine, Universidade de Sao Paulo Faculdade de Medicina de Ribeirao Preto, Ribeirao Preto, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Izilda","family":"Cardinalli","sequence":"additional","affiliation":[{"name":"I Cardinalli, Oncology, Boldrini Children's Center, Campinas, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos Alberto","family":"Scrideli","sequence":"additional","affiliation":[{"name":"C Scrideli, Pediatrics , Universidade de Sao Paulo Faculdade de Medicina de Ribeirao Preto, Ribeirao Preto, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thais","family":"Junqueira","sequence":"additional","affiliation":[{"name":"T Junqueira, Oncology, Boldrini Children's Center, Campinas, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos A. F.","family":"Molina","sequence":"additional","affiliation":[{"name":"C Molina, Surgery and Anatomy , Universidade de Sao Paulo Faculdade de Medicina de Ribeirao Preto, Ribeirao Preto, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando Silva","family":"Ramalho","sequence":"additional","affiliation":[{"name":"F Ramalho, Pathology, Universidade de Sao Paulo Faculdade de Medicina de Ribeirao Preto, Ribeirao Preto, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvio","family":"Tucci Junior","sequence":"additional","affiliation":[{"name":"S Tucci Junior, Surgery and Anatomy, Universidade de Sao Paulo Faculdade de Medicina de Ribeirao Preto, Ribeirao Preto, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernanda Borchers","family":"Coeli-Lacchini","sequence":"additional","affiliation":[{"name":"F Coeli-Lacchini, Internal Medicine, Universidade de Sao Paulo Faculdade de Medicina de Ribeirao Preto, Ribeirao Preto, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayrton Custodio","family":"Moreira","sequence":"additional","affiliation":[{"name":"A Moreira, Internal Medicine, Universidade de Sao Paulo Faculdade de Medicina de Ribeirao Preto, Ribeirao Preto, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leandra N Z","family":"Ramalho","sequence":"additional","affiliation":[{"name":"L Ramalho, Pathology, Universidade de Sao Paulo Faculdade de Medicina de Ribeirao Preto, Ribeirao Preto, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Brandalise","sequence":"additional","affiliation":[{"name":"S Brandalise, Oncology, Boldrini Children's Center, Campinas, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Andres","family":"Yunes","sequence":"additional","affiliation":[{"name":"J Yunes, Oncology, Boldrini Children's Center, Campinas, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret","family":"De Castro","sequence":"additional","affiliation":[{"name":"M De Castro, Internal Medicine, Universidade de Sao Paulo Faculdade de Medicina de Ribeirao Preto, Ribeirao Preto, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo Zorzetto Nicoliello","family":"V\u00eancio","sequence":"additional","affiliation":[{"name":"R V\u00eancio, Computation and Mathematics, University of Sao Paulo Faculty of Philosophy Sciences and Letters of Ribeirao Preto, Ribeirao Preto, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonir R R","family":"Antonini","sequence":"additional","affiliation":[{"name":"S Antonini, Pediatrics, Universidade de Sao Paulo Faculdade de Medicina de Ribeirao Preto, Ribeirao Preto, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","container-title":["Endocrine-Related Cancer"],"original-title":[],"link":[{"URL":"https:\/\/erc.bioscientifica.com\/view\/journals\/erc\/aop\/erc-22-0145\/erc-22-0145.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/erc.bioscientifica.com\/downloadpdf\/journals\/erc\/aop\/erc-22-0145\/erc-22-0145.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/erc.bioscientifica.com\/downloadpdf\/journals\/erc\/aop\/erc-22-0145\/erc-22-0145.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:56:18Z","timestamp":1784555778000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.bioscientifica.com\/erc\/article\/29\/11\/599-613\/25618"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1530\/erc-22-0145","relation":{},"ISSN":["1351-0088","1479-6821"],"issn-type":[{"value":"1351-0088","type":"print"},{"value":"1479-6821","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8]]}}}