Cancer Cell 2017 09;32(3):273-275
Pediatric Oncology Branch, National Cancer Institute, Center for Cancer Research, 9000 Rockville Pike, Bethesda, MD 20892, USA. Electronic address:
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Cancer Cell 2017 09 31;32(3):310-323.e5. Epub 2017 Aug 31.
Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA. Electronic address:
A genome-wide association study identified LMO1, which encodes an LIM-domain-only transcriptional cofactor, as a neuroblastoma susceptibility gene that functions as an oncogene in high-risk neuroblastoma. Here we show that dβh promoter-mediated expression of LMO1 in zebrafish synergizes with MYCN to increase the proliferation of hyperplastic sympathoadrenal precursor cells, leading to a reduced latency and increased penetrance of neuroblastomagenesis. The transgenic expression of LMO1 also promoted hematogenous dissemination and distant metastasis, which was linked to neuroblastoma cell invasion and migration, and elevated expression levels of genes affecting tumor cell-extracellular matrix interaction, including loxl3, itga2b, itga3, and itga5. Read More
Mol Carcinog 2011 Jun 28;50(6):403-11. Epub 2010 Dec 28.
Departments of Cancer Genetics, Royal College of Surgeons in Ireland, York House, Dublin, Ireland.
Amplification of the oncogenic transcription factor MYCN plays a major role in the pathogenesis of several pediatric cancers, including neuroblastoma, medulloblastoma, and rhabodomyosarcoma. For neuroblastoma, MYCN amplification is the most powerful genetic predictor of poor patient survival, yet the mechanism by which MYCN drives tumorigenesis is only partially understood. To gain an insight into the distribution of MYCN binding and to identify clinically relevant MYCN target genes, we performed an integrated analysis of MYCN ChIP-chip and mRNA expression using the MYCN repressible SHEP-21N neuroblastoma cell line. Read More
Neoplasia 2009 Aug;11(8):753-62
Texas Children's Cancer Center and Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX 77030, USA.
Neuroblastoma is derived from neural crest precursor components of the peripheral sympathetic nervous system and accounts for more than 15% of all pediatric cancer deaths. A clearer understanding of the molecular basis of neuroblastoma is required for novel therapeutic approaches to improve morbidity and mortality. Neuroblastoma is uniformly p53 wild type at diagnosis and must overcome p53-mediated tumor suppression during pathogenesis. Read More
Cancer Lett 2016 Feb 10;371(2):214-24. Epub 2015 Dec 10.
Oncogenomics Section, Genetics Branch, National Cancer Institute, National Institute of Health, Bethesda, MD 20892, USA. Electronic address:
The molecular mechanisms underlying the aggressive behavior of MYCN driven neuroblastoma (NBL) is under intense investigation; however, little is known about the impact of this family of transcription factors on the splicing program. Here we used high-throughput RNA sequencing to systematically study the expression of RNA isoforms in stage 4 MYCN-amplified NBL, an aggressive subtype of metastatic NBL. We show that MYCN-amplified NBL tumors display a distinct gene splicing pattern affecting multiple cancer hallmark functions. Read More