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  • Oncogenomics
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NORE1A, a homologue of RASSF1A tumour suppressor gene is inactivated in human cancers

Oncogene volume 22, pages 947–954 (2003)Cite this article

Abstract

We recently demonstrated that RASSF1A, a new tumour-suppressor gene located at 3p21.3 is frequently inactivated by promoter region hypermethylation in a variety of human cancers including lung, breast, kidney and neuroblastoma. We have identified another member of the RASSF1 gene family by in silico sequence analysis using BLAST searches. NORE1 located at 1q32.1 exists in three isoforms (NORE1Aα, NORE1Aβ and NORE1B). Both NORE1A and NORE1B isoforms have separate CpG islands spanning their first exons. NORE1Aα Produces a 418 aa protein containing a Ras-association (RA) domain and a diacylglycerol (DAG) binding domain. NORE1Aβ produces a C-terminal truncation of the RA domain. NORE1B also contains the RA domain but not the DAG domain. NORE1 is the human homologue of the mouse Ras effector Nore1. No inactivating somatic mutations were found in lung tumour lines; however, NORE1A promoter region CpG island was hypermethylated in primary tumours and tumour cell lines. NORE1A promoter was methylated in 10/25 breast, 4/40 SCLC, 3/17 NSCLC, 1/6 colorectal and 3/9 kidney tumour cell lines, while NORE1B promoter was unmethylated in the same tumour cell lines. While 24% (6/25) of primary NSCLC underwent NORE1A methylation, methylation in SCLC was a rare event (0/22); (P=0.0234). NORE1A expression in tumour cell lines was reactivated after treatment with a demethylating agent. There was no correlation between NORE1A and RASSF1A methylation status in NSCLC. Our results demonstrate that NORE1A is inactivated in a subset of human cancers by CpG island promoter hypermethylation, and in lung cancer this hypermethylation may be histological type specific.

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Acknowledgements

This work is supported in part by the Cancer Research UK. JDM supported by SPORE P50CA70907. The colorectal tumour cell lines were provided by Ian P M Tomlinson.

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Authors and Affiliations

  1. Department of Paediatrics and Child Health, Section of Medical and Molecular Genetics, University of Birmingham, The Medical School, Birmingham, B15 2TT, Edgbaston, UK

    Luke Hesson, Ashraf Dallol, Eamonn R Maher & Farida Latif

  2. Hamon Center for Therapeutic Oncology Research, UT Southwestern Medical Center, Dallas, 75390, TX, USA

    John D Minna

  3. Cancer Research UK Renal Molecular Oncology Research Group, University of Birmingham, The Medical School, Birmingham, B15 2TT, UK

    Eamonn R Maher & Farida Latif

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  1. Luke Hesson
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  2. Ashraf Dallol
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Correspondence to Farida Latif.

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Hesson, L., Dallol, A., Minna, J. et al. NORE1A, a homologue of RASSF1A tumour suppressor gene is inactivated in human cancers. Oncogene 22, 947–954 (2003). https://doi.org/10.1038/sj.onc.1206191

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