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

ABSTRACT: 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.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).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.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.

SUBMITTER: Buckley PG

PROVIDER: S-EPMC2880207 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature

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

Buckley Patrick G PG Alcock Leah L Bryan Kenneth K Bray Isabella I Schulte Johannes H JH Schramm Alexander A Eggert Angelika A Mestdagh Pieter P De Preter Katleen K Vandesompele Jo J Speleman Frank F Stallings Raymond L RL

Clinical cancer research : an official journal of the American Association for Cancer Research 20100420 11

<h4>Purpose</h4>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.<h4>Experimental design</h4>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 expre ...[more]

PMID: 20406844

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Project description:BackgroundCutaneous squamous cell carcinoma (CSCC) is the second most widespread cancer in humans and its incidence is rising. These tumours can evolve as diseases of poor prognosis, and therefore it is important to identify new markers to better predict its clinical evolution.ObjectivesWe aimed to identify the expression pattern of microRNAs (miRNAs or miRs) at different stages of skin cancer progression in a panel of murine skin cancer cell lines. Owing to the increasing importance of miRNAs in the pathogenesis of cancer, we considered the possibility that miRNAs could help to define the prognosis of CSCC and aimed to evaluate the potential use of miR-203 and miR-205 as biomarkers of prognosis in human tumours.MethodsSeventy-nine human primary CSCCs were collected at the University Hospital of Salamanca in Spain. We identified differential miRNA expression patterns at different stages of CSCC progression in a well-established panel of murine skin cancer cell lines, and then selected miR-205 and miR-203 to evaluate their association with the clinical prognosis and evolution of human CSCC.ResultsmiR-205 was expressed in tumours with pathological features recognized as indicators of poor prognosis such as desmoplasia, perineural invasion and infiltrative growth pattern. miR-205 was mainly expressed in undifferentiated areas and in the invasion front, and was associated with both local recurrence and the development of general clinical events of poor evolution. miR-205 expression was an independent variable selected to predict events of poor clinical evolution using the multinomial logistic regression model described in this study. In contrast, miR-203 was mainly expressed in tumours exhibiting the characteristics associated with a good prognosis, was mainly present in well-differentiated zones, and rarely expressed in the invasion front. Therefore, the expression and associations of miR-205 and miR-203 were mostly mutually exclusive. Finally, using a logistic biplot we identified three clusters of patients with differential prognosis based on miR-203 and miR-205 expression, and pathological tumour features.ConclusionsmiR-205 and miR-203 tended to exhibit mutually exclusive expression patterns in human CSCC. This work highlights the utility of miR-205 and miR-203 as prognostic markers in CSCC.

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

Publications

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

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