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:
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Cell Rep 2017 03;18(12):2932-2942
Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Mayo Clinic Cancer Center, Rochester, MN 55902, USA; Department of Molecular Pharmacology and Experimental Therapeutics, Center for Individualized Medicine, Mayo Clinic College of Medicine, Rochester, MN 55902, USA. Electronic address:
Growing evidence suggests a major role for Src-homology-2-domain-containing phosphatase 2 (SHP2/PTPN11) in MYCN-driven high-risk neuroblastoma, although biologic confirmation and a plausible mechanism for this contribution are lacking. Using a zebrafish model of MYCN-overexpressing neuroblastoma, we demonstrate that mutant ptpn11 expression in the adrenal gland analog of MYCN transgenic fish promotes the proliferation of hyperplastic neuroblasts, accelerates neuroblastomagenesis, and increases tumor penetrance. We identify a similar mechanism in tumors with wild-type ptpn11 and dysregulated Gab2, which encodes a Shp2 activator that is overexpressed in human neuroblastomas. Read More
Oncotarget 2016 Aug;7(34):54937-54951
Children's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales, Sydney, Australia.
Amplification of the MYCN oncogene, a member of the MYC family of transcriptional regulators, is one of the most powerful prognostic markers identified for poor outcome in neuroblastoma, the most common extracranial solid cancer in childhood. While MYCN has been established as a key driver of malignancy in neuroblastoma, the underlying molecular mechanisms are poorly understood. Transcription factor activating enhancer binding protein-4 (TFAP4) has been reported to be a direct transcriptional target of MYC. Read More
Nature 2011 Jan 1;469(7329):216-20. Epub 2010 Dec 1.
The Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
Neuroblastoma is a childhood cancer of the sympathetic nervous system that accounts for approximately 10% of all paediatric oncology deaths. To identify genetic risk factors for neuroblastoma, we performed a genome-wide association study (GWAS) on 2,251 patients and 6,097 control subjects of European ancestry from four case series. Here we report a significant association within LIM domain only 1 (LMO1) at 11p15. Read More
Cell Death Dis 2017 Dec 13;8(12):3208. Epub 2017 Dec 13.
Department of Pediatrics, C.S. Mott Children and Women's Hospital, The University of Michigan Medical School, Ann Arbor, MI, USA.
Neuroblastoma is a cancer of neural crest stem cell (NCSC) lineage. Signaling pathways that regulate NCSC differentiation have been implicated in neuroblastoma tumorigenesis. This is exemplified by MYCN oncogene targets that balance proliferation, differentiation, and cell death similarly in normal NCSC and in high-risk neuroblastoma. Read More