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  • Original Paper
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Loss of methylation at chromosome 11p15.5 is common in human adult tumors

Oncogene volume 21, pages 2564–2572 (2002)Cite this article

Abstract

Chromosome 11p15 deletion is frequent in human tumors, suggesting the presence of at least one tumor suppressor gene within this region. While mutation analyses of local genes revealed only rare mutations, we have previously described a mechanism, gain of imprinting, that leads to loss of expression of genes located on the maternal 11p15 chromosome in human hepatocarcinomas. Loss of expression was often associated with loss of maternal-specific methylation at the KvDMR1 locus. Here, we show that loss of the maternal KvDMR1 methylation is common, ranging from 30 to 50%, to a variety of adult neoplasms, including liver, breast, cervical and gastric carcinomas. We found that other 11p15.5 loci were concomitantly hypomethylated, indicating that loss of KvDMR1 methylation occurred in the context of a common mechanism affecting the methylation of a large 11p15 subchromosomal domain. These epigenetic abnormalities were not detected in any normal somatic tissue. Therefore, it seems possible that, contrary to the repression of promoter activity caused by hypermethylation, loss of gene expression at 11p15.5 may result from the activation, by hypomethylation, of one or more negative regulatory elements.

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Acknowledgements

We thank Augusto Bevilacqua and Pietro Zucchini for the excellent technical assistance. RAM Scelfo is supported by a fellowship from Fondazione Italiana per la Ricerca sul Cancro (FIRC). This work was supported by grants from Associazione Italiana per la Ricerca sul Cancro (AIRC), Milan, Italy and from MURST ex-60%.

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Authors and Affiliations

  1. Dipartimento di Medicina Sperimentale e Diagnostica, Università di Ferrara, Ferrara, Italy

    Rosaria AM Scelfo, Christine Schwienbacher, Patrizia Querzoli, Italo Nenci, Giuseppe Barbanti-Brodano & Massimo Negrini

  2. Centro Interdipartmentale per la Ricerca sul Cancro, Università di Ferrara, Ferrara, Italy

    Patrizia Querzoli & Massimo Negrini

  3. International Cancer Center, Molecular Biology Laboratories, Azienda ULSS 18, Rovigo, Italy

    Angelo Veronese & Massimo Negrini

  4. Dipartimento di Medicina Interna e Gastroenterologia, Università di Bologna, Bologna, Italy

    Laura Gramantieri & Luigi Bolondi

  5. Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania, USA

    George A Calin

  6. Ospedale Pediatrico del Bambino Gesu IRCCS, Servizio Immunotrasfusionale, Roma, Italy

    Adriano Angioni

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  1. Rosaria AM Scelfo
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  2. Christine Schwienbacher
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Correspondence to Massimo Negrini.

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Scelfo, R., Schwienbacher, C., Veronese, A. et al. Loss of methylation at chromosome 11p15.5 is common in human adult tumors. Oncogene 21, 2564–2572 (2002). https://doi.org/10.1038/sj.onc.1205336

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