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Tumor-specific exon 1 mutations could be the ‘hit event’ predisposing Rb2/p130 gene to epigenetic silencing in lung cancer

Oncogene volume 24, pages 5821–5826 (2005)Cite this article

Abstract

Genetic alterations in Rb2/p130 gene have been reported in several tumors, but till now there are insufficient and conflicting data linking the loss of pRb2/p130 expression with the mutational status of this gene in lung cancer. We recently reported that loss or lowering of pRb2/p130 expression is mainly due to aberrant Rb2/p130 promoter methylation, in retinoblastoma tumors, and indicated that epigenetic silencing of Rb2/p130 can impair its function to negatively regulate cell cycle progression as well as apoptotic response. In order to clarify Rb2/p130 gene inactivation in lung cancer, we investigated whether epigenetic events could impair the expression of this gene in NSLC. Here, we show that specific Rb2-exon 1 homozygous mutations, occurring in an Rb2/p130, region, rich in CpG dinucleotides, could be the ‘hit event’ that predispose this gene to epigenetic changes, leading to Rb2/p130 gene silencing in lung cancer. Moreover, these homozygous mutations, found in different tumor histotypes, could represent tumor-specific markers.

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Acknowledgements

We thank Dr D La Sala and Dr A Zamparelli for technical help and Dr C Trimarchi for helpful and constructive comments on the manuscript. This study was supported by NIH-RO1 CA066999-09A2 grant, Sbarro Health Research Organization (WWW.SHRO.ORG) and AIRC grants to AG, and by Murst Lag-CO3, Consiglio Nazionale delle Ricerche (CNR), Ministero della Sanita' grants to CC. Dr Marcella Macaluso is supported by an FIRC (Fondazione Italiana per la Ricerca sul Cancro) fellowship.

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Authors and Affiliations

  1. Institute of Clinical Physiology, CNR, Siena Unity, Italy

    Cinti Caterina

  2. Sbarro Institute for Cancer Research and Molecular Medicine, Center of Biotechnology, College of Science and Technology, Temple University, Philadelphia, 19122, PA, USA

    Cinti Caterina, Macaluso Marcella & Antonio Giordano

  3. Department of Human Pathology and Oncology University of Siena, Siena, Italy

    Macaluso Marcella & Antonio Giordano

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  1. Cinti Caterina
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Correspondence to Antonio Giordano.

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Caterina, C., Marcella, M. & Giordano, A. Tumor-specific exon 1 mutations could be the ‘hit event’ predisposing Rb2/p130 gene to epigenetic silencing in lung cancer. Oncogene 24, 5821–5826 (2005). https://doi.org/10.1038/sj.onc.1208880

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