Novel amplicons in pediatric medulloblastoma identified by high-resolution genomic analysis: Genetic aberrations in medulloblastoma
(English)Manuscript (preprint) (Other academic)
Medulloblastoma (MB) is an aggressive and invasive embryonal CNS tumor that mainly affects children. Despite treatment, ~30% of the patients die within 2 years from diagnosis. MB patients are currently categorized into high- or standard-risk based on the clinical criteria, with high-risk group including patients <3 years, with incomplete tumor resection or with concomitant metastatic disease at presentation. However, these clinical parameters do not always predict patient outcome and additional biomarkers are desirable. In this study we have profiled a series of 25 MB samples with a high-resolution 32K BAC-array covering 99% of the current assembly of the human genome for the identification of genetic copy number alterations. The most frequent observed alteration was the combination of 17p loss and 17q gain, indicative of an isochromosome 17q, which was identified in 40% of the patients. This aberration was detected in both high- and standard-risk groups and was not associated with worse outcome. We also defined minimal overlapping regions of aberrations, including 16 regions of gains and 18 regions of loss in different chromosomes. Noteworthy, are a few very narrow amplified loci identified on autosomes 1, 3 and 8, aberrations that were verified with an alternative platform (Illumina 610Q chips). Several genes as CYR61, LMO4, EOMES, and MLH1 encompassed within these loci were also found to present with transcript up-regulation. These genes represent novel candidate genes most probably involved in MB development.
Research subject Medical Genetics
IdentifiersURN: urn:nbn:se:uu:diva-121954OAI: oai:DiVA.org:uu-121954DiVA: diva2:306950