Chromosomal and microRNA expression patterns reveal biologically distinct subgroups of 11q- neuroblastoma.

Abstract

PURPOSE:

The purpose of this study was to further define the biology of the 11q- neuroblastoma tumor subgroup by the integration of array-based comparative genomic hybridization with microRNA (miRNA) expression profiling data to determine if improved patient stratification is possible.

EXPERIMENTAL DESIGN:

A set of primary neuroblastoma (n = 160), which was broadly representative of all genetic subtypes, was analyzed by array-based comparative genomic hybridization and for the expression of 430 miRNAs. A 15-miRNA expression signature previously shown to be predictive of clinical outcome was used to analyze an independent cohort of 11q- tumors (n = 37).

RESULTS:

Loss of 4p and gain of 7q occurred at a significantly higher frequency in the 11q- tumors, further defining the genetic characteristics of this subtype. The 11q- tumors could be split into two subgroups using a miRNA expression survival signature that differed significantly in clinical outcome and the overall frequency of large-scale genomic imbalances, with the poor survival subgroup having significantly more imbalances. miRNAs from the expression signature, which were upregulated in unfavorable tumors, were predicted to target downregulated genes from a published mRNA expression classifier of clinical outcome at a higher-than-expected frequency, indicating the miRNAs might contribute to the regulation of genes within the signature.

CONCLUSION:

We show that two distinct biological subtypes of neuroblastoma with loss of 11q occur, which differ in their miRNA expression profiles, frequency of segmental imbalances, and clinical outcome. A miRNA expression signature, combined with an analysis of segmental imbalances, provides greater prediction of event-free survival and overall survival outcomes than 11q status by itself, improving patient stratification.

• Authors: Patrick G Buckley, Leah Alcock, Kenneth Bryan, Isabella Bray, Johannes H Schulte, Alexander Schramm, Angelika Eggert, Pieter Mestdagh, Katleen De Preter, Jo Vandesompele, Frank Speleman, Raymond L Stallings
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 16 Issue 11 Pg. 2971-8 (Jun 01 2010) ISSN: 1557-3265 [Electronic] United States
• PMID: 20406844 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2010 AACR.

Chemical References

• MicroRNAs

Topics

• Chromosome Deletion
• Chromosomes, Human, Pair 11
• Disease-Free Survival
• Gene Dosage
• Gene Expression Profiling
• Humans
• MicroRNAs (metabolism)
• Neuroblastoma (classification, genetics)