Real-time PCR assay based on the differential expression of microRNAs and protein-coding genes for molecular classification of formalin-fixed paraffin embedded medulloblastomas

Medulloblastoma has recently been found to consist of 4 molecularly and clinically distinct subgroups: WNT, Sonce hedgehog (SHH), Group 3, and Group 4. Deregulated microRNA expression is known to contribute to pathogenesis and has been shown to have diagnostic and prognostic potential in the classif...

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Veröffentlicht in:Neuro-oncology (Charlottesville, Va.) Va.), 2013-12, Vol.15 (12), p.1644-1651
Hauptverfasser: Kunder, Ratika, Jalali, Rakesh, Sridhar, Epari, Moiyadi, Aliasgar, Goel, Naina, Goel, Atul, Gupta, Tejpal, Krishnatry, Rahul, Kannan, Sadhana, Kurkure, Purna, Deopujari, Chandrashekhar, Shetty, Prakash, Biyani, Naresh, Korshunov, Andrey, Pfister, Stefan M, Northcott, Paul A, Shirsat, Neelam Vishwanath
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container_issue 12
container_start_page 1644
container_title Neuro-oncology (Charlottesville, Va.)
container_volume 15
creator Kunder, Ratika
Jalali, Rakesh
Sridhar, Epari
Moiyadi, Aliasgar
Goel, Naina
Goel, Atul
Gupta, Tejpal
Krishnatry, Rahul
Kannan, Sadhana
Kurkure, Purna
Deopujari, Chandrashekhar
Shetty, Prakash
Biyani, Naresh
Korshunov, Andrey
Pfister, Stefan M
Northcott, Paul A
Shirsat, Neelam Vishwanath
description Medulloblastoma has recently been found to consist of 4 molecularly and clinically distinct subgroups: WNT, Sonce hedgehog (SHH), Group 3, and Group 4. Deregulated microRNA expression is known to contribute to pathogenesis and has been shown to have diagnostic and prognostic potential in the classification of various cancers. Molecular subgrouping and microRNA expression analysis of 44 frozen and 59 formalin-fixed paraffin embedded medulloblastomas from an Indian cohort were carried out by real-time RT-PCR assay. The differential expression of 9 microRNAs in the 4 molecular subgroups was validated in a set of 101 medulloblastomas. The tumors in the WNT subgroup showed significant (P < .0001) overexpression of miR-193a-3p, miR-224, miR-148a, miR-23b, and miR-365. Reliable classification of medulloblastomas into the 4 molecular subgroups was obtained using a set of 12 protein-coding genes and 9 microRNAs as markers in a real-time RT-PCR assay with an accuracy of 97% as judged by the Prediction Analysis of Microarrays. Age at diagnosis, histology, gender-related incidence, and the relative survival rates of the 4 molecular subgroups in the present Indian cohort were found to be similar to those reported for medulloblastomas from the American and European subcontinent. Non-WNT, non-SHH medulloblastomas underexpressing miR-592 or overexpressing miR-182 were found to have significantly inferior survival rates, indicating utility of these miRNAs as markers for risk stratification. The microRNA based real-time PCR assay is rapid, simple, inexpensive, and useful for molecular classification and risk stratification of medulloblastomas, in particular formalin-fixed paraffin embedded tissues, wherein the expression profile of protein-coding genes is often less reliable due to RNA fragmentation.
doi_str_mv 10.1093/neuonc/not123
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Deregulated microRNA expression is known to contribute to pathogenesis and has been shown to have diagnostic and prognostic potential in the classification of various cancers. Molecular subgrouping and microRNA expression analysis of 44 frozen and 59 formalin-fixed paraffin embedded medulloblastomas from an Indian cohort were carried out by real-time RT-PCR assay. The differential expression of 9 microRNAs in the 4 molecular subgroups was validated in a set of 101 medulloblastomas. The tumors in the WNT subgroup showed significant (P &lt; .0001) overexpression of miR-193a-3p, miR-224, miR-148a, miR-23b, and miR-365. Reliable classification of medulloblastomas into the 4 molecular subgroups was obtained using a set of 12 protein-coding genes and 9 microRNAs as markers in a real-time RT-PCR assay with an accuracy of 97% as judged by the Prediction Analysis of Microarrays. Age at diagnosis, histology, gender-related incidence, and the relative survival rates of the 4 molecular subgroups in the present Indian cohort were found to be similar to those reported for medulloblastomas from the American and European subcontinent. Non-WNT, non-SHH medulloblastomas underexpressing miR-592 or overexpressing miR-182 were found to have significantly inferior survival rates, indicating utility of these miRNAs as markers for risk stratification. 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Age at diagnosis, histology, gender-related incidence, and the relative survival rates of the 4 molecular subgroups in the present Indian cohort were found to be similar to those reported for medulloblastomas from the American and European subcontinent. Non-WNT, non-SHH medulloblastomas underexpressing miR-592 or overexpressing miR-182 were found to have significantly inferior survival rates, indicating utility of these miRNAs as markers for risk stratification. 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ispartof Neuro-oncology (Charlottesville, Va.), 2013-12, Vol.15 (12), p.1644-1651
issn 1522-8517
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source MEDLINE; Oxford University Press Journals All Titles (1996-Current); PubMed Central; EZB Electronic Journals Library
subjects Adolescent
Adult
Basic and Translational Investigations
Case-Control Studies
Cerebellar Neoplasms - classification
Cerebellar Neoplasms - genetics
Cerebellar Neoplasms - mortality
Cerebellar Neoplasms - pathology
Cerebellum - metabolism
Cerebellum - pathology
Child
Child, Preschool
Female
Follow-Up Studies
Gene Expression Profiling
Hedgehog Proteins - genetics
Hedgehog Proteins - metabolism
Humans
Infant
Male
Medulloblastoma - classification
Medulloblastoma - genetics
Medulloblastoma - mortality
Medulloblastoma - pathology
MicroRNAs - genetics
Middle Aged
Neoplasm Staging
Oligonucleotide Array Sequence Analysis
Paraffin Embedding
Prognosis
Real-Time Polymerase Chain Reaction - methods
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - genetics
Survival Rate
Wnt Proteins - genetics
Wnt Proteins - metabolism
Young Adult
title Real-time PCR assay based on the differential expression of microRNAs and protein-coding genes for molecular classification of formalin-fixed paraffin embedded medulloblastomas
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