| Texto completo | |
| Autor(es): |
de Sa Pereira, Bruna M.
[1, 2]
;
Montalvao-de-Azevedo, Rafaela
[1, 2]
;
Faria, Paulo Antonio
[3]
;
Silva, Neimar de Paula
[2, 1]
;
Nicolau-Neto, Pedro
[4]
;
Maschietto, Mariana
[5]
;
de Camargo, Beatriz
[1]
;
Soares Lima, Sheila Coelho
[4]
Número total de Autores: 8
|
| Afiliação do(s) autor(es): | [1] Inst Nacl Canc INCA, Pediat Hematol Oncol Res Program, Res Ctr CPQ, Rua Andre Cavalcanti 37, BR-20231050 Rio De Janeiro - Brazil
[2] Inst Nacl Canc INCA, Post Grad Program, Rio De Janeiro - Brazil
[3] Inst Nacl Canc DIPAT INCA, Div Pathol, Rua Cordeiro Graca 156, BR-20220400 Rio De Janeiro - Brazil
[4] Inst Nacl Canc INCA, Mol Carcinogenesis Program, Res Ctr CPQ, Rua Andre Cavalcanti 37, BR-20231050 Rio De Janeiro - Brazil
[5] Brazilian Biosci Natl Lab LNBio, Brazilian Ctr Res Energy & Mat CNPEM, Rua Giuseppe Maximo Scolfaro 10-000, BR-13083970 Sao Paulo - Brazil
Número total de Afiliações: 5
|
| Tipo de documento: | Artigo Científico |
| Fonte: | CLINICAL EPIGENETICS; v. 9, DEC 12 2017. |
| Citações Web of Science: | 3 |
| Resumo | |
Background: Wilms tumor (WT) is a curable pediatric renal malignancy, but there is a need for new molecular biomarkers to improve relapse risk-directed therapy. Somatic alterations occur at relatively low frequencies whereas epigenetic changes at 11p15 are the most common aberration. We analyzed long interspersed element-1 (LINE-1) methylation levels in the blastemal component of WT and normal kidney samples to explore their prognostic significance. Results: WT samples presented a hypomethylated pattern at all five CpG sites compared to matched normal kidney samples; therefore, the averaged methylation levels of the five CpG sites were used for further analyses. WT presented a hypomethylation profile (median 65.0%, 47.4-73.2%) compared to normal kidney samples (median 71.8%, 51.5-77. 5%; p < 0.0001). No significant associations were found between LINE-1 methylation levels and clinical-pathological characteristics. We observed that LINE-1 methylation levels were lower in tumor samples from patients with relapse (median methylation 60.5%) compared to patients without relapse (median methylation 66.5%; p = 0.0005), and a receiving operating characteristic curve analysis was applied to verify the ability of LINE-1 methylation levels to discriminate WT samples from these patients. Using a cut-off value of 62.71% for LINE-1 methylation levels, the area under the curve was 0.808, with a sensitivity of 76.5% and a specificity of 83.3%. Having identified differences in LINE-1 methylation between WT samples from patients with and without relapse in this cohort, we evaluated other prognostic factors using a logistic regression model. This analysis showed that in risk stratification, LINE-1 methylation level was an independent variable for relapse risk: the lower the methylation levels, the higher the risk of relapse. The logistic regression model indicated a relapse risk increase of 30% per decreased unit of methylation (odds ratio 1.30; 95% confidence interval 1.07-1.57). Conclusion: Our results reinforce previous data showing a global hypomethylation profile in WT. LINE-1 methylation levels can be suggested as a marker of relapse after chemotherapy treatment in addition to risk classification, helping to guide new treatment approaches. (AU) | |
| Processo FAPESP: | 15/06281-7 - Investigação da regulação epigenética em tumores sólidos pediátricos |
| Beneficiário: | Mariana Camargo Maschietto |
| Linha de fomento: | Bolsas no Brasil - Apoio a Jovens Pesquisadores |