Integrated genomic analyses identify ARID1A and ARID1B alterations in the childhood cancer neuroblastoma View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2013-01

AUTHORS

Mark Sausen, Rebecca J Leary, Siân Jones, Jian Wu, C Patrick Reynolds, Xueyuan Liu, Amanda Blackford, Giovanni Parmigiani, Luis A Diaz, Nickolas Papadopoulos, Bert Vogelstein, Kenneth W Kinzler, Victor E Velculescu, Michael D Hogarty

ABSTRACT

Neuroblastomas are tumors of peripheral sympathetic neurons and are the most common solid tumor in children. To determine the genetic basis for neuroblastoma, we performed whole-genome sequencing (6 cases), exome sequencing (16 cases), genome-wide rearrangement analyses (32 cases) and targeted analyses of specific genomic loci (40 cases) using massively parallel sequencing. On average, each tumor had 19 somatic alterations in coding genes (range of 3-70). Among genes not previously known to be involved in neuroblastoma, chromosomal deletions and sequence alterations of the chromatin-remodeling genes ARID1A and ARID1B were identified in 8 of 71 tumors (11%) and were associated with early treatment failure and decreased survival. Using tumor-specific structural alterations, we developed an approach to identify rearranged DNA fragments in sera, providing personalized biomarkers for minimal residual disease detection and monitoring. These results highlight the dysregulation of chromatin remodeling in pediatric tumorigenesis and provide new approaches for the management of patients with neuroblastoma. More... »

PAGES

12

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    URI

    http://scigraph.springernature.com/pub.10.1038/ng.2493

    DOI

    http://dx.doi.org/10.1038/ng.2493

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1033735592

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/23202128


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