Two independent epigenetic biomarkers predict survival in neuroblastoma

Clinical Epigenetics
Yania YañezVictoria Castel

Abstract

Neuroblastoma (NB) is the most common extracranial pediatric solid tumor with a highly variable clinical course, ranging from spontaneous regression to life-threatening disease. Survival rates for high-risk NB patients remain disappointingly low despite multimodal treatment. Thus, there is an urgent clinical need for additional biomarkers to improve risk stratification, treatment management, and survival rates in children with aggressive NB. Using gene promoter methylation analysis in 48 neuroblastoma tumors with microarray technology, we found a strong association between survival and gene promoter hypermethylation (P = 0.036). Hypermethylation of 70 genes significantly differentiated high-risk survivor patients from those who died during follow-up time. Sixteen genes with relevant roles in cancer biology were further validated in an additional cohort of 83 neuroblastoma tumors by bisulfite pyrosequencing. High promoter methylation rates of these genes were found in patients with metastatic tumors (either stage metastatic (M) or metastatic special (MS)), 18 months or older at first diagnosis, MYCN amplification, relapsed, and dead. Notably, the degree of methylation of retinoblastoma 1 (RB1) and teratocarcinoma-derived growth ...Continue Reading

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Citations

Nov 26, 2015·Pediatric Blood & Cancer·Julie H HarreldMary E Hoehn
Feb 2, 2017·Journal of Cellular Physiology·Sharareh GholaminAmir Avan
Nov 28, 2018·Current Opinion in Pediatrics·Suzanne MacFarland, Rochelle Bagatell
Aug 2, 2019·Pediatric Blood & Cancer·Jaques Van HeerdenMariana Kruger
May 20, 2015·Asian Pacific Journal of Cancer Prevention : APJCP·Meng XuHuan-Zhi Zhang
Nov 28, 2018·Pediatric Blood & Cancer·Daniel A MorgensternMeredith S Irwin

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Methods Mentioned

BETA
methylation profiling
PCR
Assay

Software Mentioned

R
BeadStudio
INRG
minAS
ENQUA
PyroMark Assay Design
R2
package glmnet

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