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Cloning of breakpoints in and downstream the IGF2 gene that are associated with overexpression of IGF2 transcripts in colorectal tumours

Oncogene volume 18, pages 4710–4717 (1999)Cite this article

Abstract

The human IGF2 gene belongs to a group of imprinted genes clustered on the short arm of chromosome 11, band p15.5. It contains 9 exons and spans over 30 kb. IGF2 mRNA overexpression has been reported in human tumours and in some inherited growth disorders. It was recently demonstrated that IGF2 mRNA overexpression contributes to tumour progression and that loss of parental imprinting as well as altered transcription factors are contributing to this overexpression. We have reported structural alterations in the 3′ region of the IGF2 gene in two colorectal tumours that overexpressed the IGF2 transcript by 200- and 800-fold. We cloned by the vectorette-PCR strategy, genomic DNA fragments containing the breakpoints from these tumours. The sequencing of these fragments positioned the breakpoint 2 kb downstream the IGF2 gene in one tumour, and in exon 9 in the second. Both breakpoints occurred in regions containing repetitive elements: a TGGA repeat we have identified downstream the gene, and the (CA)n repetition in exon 9. We hypothesize that a negative regulatory element, located downstream the IGF2 gene, has been deleted following these structural alterations and leads to IGF2 gene overexpression.

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Acknowledgements

This work was supported by a grant form the Belgian ‘Fonds National pour la Recherche Scientifique (FNRS.)’, ‘Association sportive contre le cancer’, ‘Association contre le Cancer’, ‘Centre Anticancéreux près l'Université de Liège’ and ‘Fondation Léon Fredericq’. R Winkler is ‘Chercheur Qualifié’ of the FNRS. D Hodzic and M Grooteclaes are recipients of ‘Télévie’ grants from the FNRS.

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  1. Didier Hodzic

    Present address: Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7170, North Carolina, USA

Authors and Affiliations

  1. Department of Pathology, Laboratory of Molecular Oncology, University of Liège, Tour de Pathologie B23, Sart Tilman, Liège, B-4000, Belgium

    Didier Hodzic, Madeleine Grooteclaes & Rosita Winkler

  2. Roche Molecular Biochemicals, Munchen, Germany

    Bruno Frey

  3. Eurogentec, Parc Scientifique du Sart Tilman, Seraing, 4102, Belgium

    Daniel Marechal & Thierry Scarcez

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  1. Didier Hodzic
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  5. Madeleine Grooteclaes
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Hodzic, D., Frey, B., Marechal, D. et al. Cloning of breakpoints in and downstream the IGF2 gene that are associated with overexpression of IGF2 transcripts in colorectal tumours. Oncogene 18, 4710–4717 (1999). https://doi.org/10.1038/sj.onc.1202877

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