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    LMO1 Synergizes with MYCN to Promote Neuroblastoma Initiation and Metastasis.
    Cancer Cell 2017 Sep 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. Our results provide in vivo validation of LMO1 as an important oncogene that promotes neuroblastoma initiation, progression, and widespread metastatic dissemination.

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    Integrative genomics identifies LMO1 as a neuroblastoma oncogene.
    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
    When LMO1 Meets MYCN, Neuroblastoma Is Metastatic.
    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:
    LMO1 is a high-risk neuroblastoma susceptibility gene, but how LMO1 cooperates with MYCN in neuroblastoma tumorigenesis is unclear. In this issue of Cancer Cell, Zhu et al. develop a novel zebrafish model that elucidates a mechanism by which LMO1 and MYCN synergistically initiate neuroblastoma and contribute to metastatic disease progression. Read More
    Glutathione biosynthesis is upregulated at the initiation of MYCN-driven neuroblastoma tumorigenesis.
    Mol Oncol 2016 06 2;10(6):866-78. Epub 2016 Mar 2.
    Children's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales, Randwick 2031, Australia; Kids Cancer Centre, Sydney Children's Hospital, Randwick 2031, Australia. Electronic address:
    The MYCN gene is amplified and overexpressed in a large proportion of high stage neuroblastoma patients and has been identified as a key driver of tumorigenesis. However, the mechanism by which MYCN promotes tumor initiation is poorly understood. Here we conducted metabolic profiling of pre-malignant sympathetic ganglia and tumors derived from the TH-MYCN mouse model of neuroblastoma, compared to non-malignant ganglia from wildtype littermates. Read More
    CTCF cooperates with noncoding RNA MYCNOS to promote neuroblastoma progression through facilitating MYCN expression.
    Oncogene 2016 Jul 9;35(27):3565-76. Epub 2015 Nov 9.
    Department of Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
    Previous studies have indicated the important roles of MYCN in tumorigenesis and progression of neuroblastoma (NB), the most common extracranial solid tumor derived from neural crest in childhood. However, the regulatory mechanisms of MYCN expression in NB still remain largely unknown. In this study, through mining public microarray databases and analyzing the cis-regulatory elements and chromatin immunoprecipitation data sets, we identified CCCTC-binding factor (CTCF) as a crucial transcription factor facilitating the MYCN expression in NB. Read More