Integrated genomic analyses identify ARID1A and ARID1B alterations in the childhood cancer neuroblastoma
Victor Velculescu, Michael Hogarty and colleagues report whole-genome and exome sequences of neuroblastoma, the most common solid tumor in children. They identify recurrent somatic mutations in the chromatin-remodeling genes ARID1A and ARID1B . Neuroblastomas are tumors of peripheral sympathetic neu...
Saved in:
Published in | Nature genetics Vol. 45; no. 1; pp. 12 - 17 |
---|---|
Main Authors | , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
New York
Nature Publishing Group US
01.01.2013
Nature Publishing Group |
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | Victor Velculescu, Michael Hogarty and colleagues report whole-genome and exome sequences of neuroblastoma, the most common solid tumor in children. They identify recurrent somatic mutations in the chromatin-remodeling genes
ARID1A
and
ARID1B
.
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. |
---|---|
Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Current Address: State Key Laboratory of Cancer Biology, Cell Engineering Research Center, The Fourth Military Medical University, Xi’an, P. R. China. These authors contributed equally to this work. Current Address: Personal Genome Diagnostics, Inc., Science and Technology Park at Johns Hopkins, Baltimore, MD 21205, USA. |
ISSN: | 1061-4036 1546-1718 |
DOI: | 10.1038/ng.2493 |