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A mechanistic classification of clinical phenotypes in neuroblastoma

ABSTRACT: Clinical courses of the pediatric tumor neuroblastoma range from fatal progression to spontaneous regression. To gain insights into the pathogenesis of these divergent subtypes, we performed massively parallel sequencing of 416 pretreatment neuroblastomas and assessed telomere maintenance mechanisms in 208/416 cases. We observed that telomere maintenance and mutations in RAS or p53 pathway genes strongly affected disease courses. Fatal outcome occurred only in the presence of telomere maintenance, whereas patients whose tumors lacked such mechanisms had excellent outcome. In patients with telomere maintenance-positive tumors, survival was dramatically inferior when additional RAS/p53 pathway mutations were present. By contrast, spontaneous regression occurred both in the presence and absence of RAS/p53 pathway mutations in patients with telomere maintenance-negative tumors. Together, our data provide a precise mechanistic classification of clinical neuroblastoma phenotypes based on telomere maintenance mechanisms and genetic alterations of the tumor.

PROVIDER: EGAS00001003244 | EGA |

REPOSITORIES: EGA

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A mechanistic classification of clinical phenotypes in neuroblastoma (TERT expression threshold cohort)

Project description:Our study proposes a precise mechanistic classification of clinical neuroblastoma phenotypes that is based on telomere maintenance mechanisms and RAS or p53 pathway mutations. A crucial factor in telomere maintenance is overexpression of TERT. We therefore determined a TERT expression threshold to identify MYCNWT TERTWT tumors whose TERT mRNA levels are comparable to those of tumors bearing MYCN or TERT alterations.

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A mechanistic classification of clinical phenotypes in neuroblastoma (telomere maintenance cohort)

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2015-04-20 | E-GEOD-56892 | biostudies-arrayexpress

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2007-11-13 | GSE9567 | GEO

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