One hit, two hits, three hits, more? Genomic changes in the development of retinoblastoma
Article first published online: 16 APR 2007
Copyright © 2007 Wiley-Liss, Inc.
Genes, Chromosomes and Cancer
Volume 46, Issue 7, pages 617–634, July 2007
How to Cite
Corson, T. W. and Gallie, B. L. (2007), One hit, two hits, three hits, more? Genomic changes in the development of retinoblastoma. Genes Chromosom. Cancer, 46: 617–634. doi: 10.1002/gcc.20457
- Issue published online: 25 APR 2007
- Article first published online: 16 APR 2007
- Manuscript Accepted: 21 MAR 2007
- Manuscript Received: 16 JAN 2007
- National Cancer Institute of Canada
- Canadian Retinoblastoma Society
- Blind Ball
The childhood eye cancer retinoblastoma is initiated by the loss of both alleles of the prototypic tumor suppressor gene, RB1. However, a large number of cytogenetic and comparative genomic hybridization (CGH) studies have shown that these M1 and M2 mutational events—although necessary for initiation—are not the only genomic changes in retinoblastoma. Some of these subsequent changes, which we have termed M3 to Mn, are likely crucial for tumor progression not only in retinoblastoma but also in other cancers. Moreover, genes showing genomic change in cancer are more stable markers and, therefore, possible therapeutic targets than genes simply differentially expressed. In this review, we provide the first comprehensive summary of the genomic evidence implicating gain of 1q, 2p, 6p, and 13q, and loss of 16q in retinoblastoma oncogenesis, including karyotype, CGH, and microarray CGH data. We discuss the search for candidate oncogenes and tumor suppressor genes within these regions, including the candidates (KIF14, MDM4, MYCN, E2F3, DEK, CDH11, and others), plus associations between genomic changes and clinical parameters. We also review studies of other regions of the retinoblastoma genome, the epigenetic changes of aberrant methylation of MGMT, RASSF1A, CASP8, and MLH1, and the roles microRNAs might play in this cancer. Although many candidate genes have yet to be functionally validated in retinoblastoma, work in this field lays out a molecular cytogenetic pathway of retinoblastoma development. Candidate cancer genes carry diagnostic, prognostic, and therapeutic implications beyond retinoblastoma. © 2007 Wiley-Liss, Inc.