دورية أكاديمية
DNA methylation is a comprehensive marker for pediatric adrenocortical tumors.
| العنوان: | DNA methylation is a comprehensive marker for pediatric adrenocortical tumors. |
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| المؤلفون: | Bueno AC; Department of Pediatrics Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil., da Silva RMP; Department of Internal Medicine Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil., Stecchini MF; Department of Pediatrics Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil., Marrero-Gutiérrez J; Department of Pediatrics Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil., de Almeida E Silva DC; Department of Internal Medicine Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil.; Department of Computation and Mathematics, Faculty of Philosophy, Sciences and Letters at Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil., Cardinalli I; Boldrini Children's Center, State University of Campinas, Campinas, Sao Paulo, Brazil., Scrideli CA; Department of Pediatrics Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil., Junqueira T; Boldrini Children's Center, State University of Campinas, Campinas, Sao Paulo, Brazil., Molina CAF; Department of Surgery and Anatomy Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil., Ramalho FS; Department of Pathology Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil., Tucci S Jr; Department of Surgery and Anatomy Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil., Coeli-Lacchini FB; Department of Internal Medicine Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil., Moreira AC; Department of Internal Medicine Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil., Ramalho LNZ; Department of Pathology Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil., Brandalise S; Boldrini Children's Center, State University of Campinas, Campinas, Sao Paulo, Brazil., Yunes JA; Boldrini Children's Center, State University of Campinas, Campinas, Sao Paulo, Brazil., de Castro M; Department of Internal Medicine Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil., Vêncio RZN; Department of Computation and Mathematics, Faculty of Philosophy, Sciences and Letters at Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil., Antonini SRR; Department of Pediatrics Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil. |
| المصدر: | Endocrine-related cancer [Endocr Relat Cancer] 2022 Sep 30; Vol. 29 (11), pp. 599-613. Date of Electronic Publication: 2022 Sep 30 (Print Publication: 2022). |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: BioScientifica Country of Publication: England NLM ID: 9436481 Publication Model: Electronic-Print Cited Medium: Internet ISSN: 1479-6821 (Electronic) Linking ISSN: 13510088 NLM ISO Abbreviation: Endocr Relat Cancer Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Jan. 2011- : Bristol, UK : BioScientifica Original Publication: Woodlands, Almondsbury, Bristol, UK : Published for the Society of Endocrinology by the Journal of Endocrinology Ltd., 1994- |
| مواضيع طبية MeSH: | Adrenal Cortex Neoplasms*/genetics , Adrenal Cortex Neoplasms*/pathology , DNA Methylation*, Biomarkers ; Biomarkers, Tumor/genetics ; Child ; CpG Islands ; Cross-Sectional Studies ; Humans ; Prognosis |
| مستخلص: | Children diagnosed with pediatric 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' clinicopathological features. We also applied our analysis in an independent 48 pACT methylation dataset. 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 with higher methylation in CpG islands, mainly in gene promoter regions. The topmost hypermethylated gene in these samples was shown to be underexpressed. Patients in the pACT-1 group were older at diagnosis and were more likely to have carcinomas and nonlocalized/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. 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. |
| فهرسة مساهمة: | Keywords: DNA methylation; pediatric adrenocortical tumor; prognosis; survival |
| المشرفين على المادة: | 0 (Biomarkers) 0 (Biomarkers, Tumor) |
| تواريخ الأحداث: | Date Created: 20220830 Date Completed: 20221004 Latest Revision: 20231105 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1530/ERC-22-0145 |
| PMID: | 36040817 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1479-6821 |
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| DOI: | 10.1530/ERC-22-0145 |