SummarySeveral tumour suppressor genes (TSG) have been identified as a result of mapping homozygous deletions in cancer cells. To identify putative TSG involved in the pathogenesis of classical Hodgkin lymphoma (cHL), we investigated four cHL cell lines (L428, HDLM2, KMH2, L1236) using four different array-Comparative Genomic Hybridisation (array-CGH) platforms and focused on high resolution identification of homozygous deletions. Out of 79 candidate regions of bi-allelic loss identified by array-CGH, besides previously described regions, 28 novel regions of homozygous deletions could be verified by polymerase chain reaction. These regions ranged from 13 kb to 619 kb in size. Eleven of the 28 novel bi-allelic losses were putative copy number polymorphisms. This left 17 regions that might harbour novel tumour suppressors involved in Hodgkin lymphoma. Expression profiling with two different platforms confirmed lack of expression of the majority of the genes located in the homozygous deletions. Furthermore, analysis of ontology annotations of genes located in the homozygously deleted regions indicated an enrichment of genes involved in apoptosis and cell death. In summary, through the mapping of homozygous deletions in cell lines this study identified a series of genes, such as SEPT9, GNG7 and CYBB, which might encode candidate tumour suppressors involved in the pathogenesis of cHL.

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Nieländer I, Bug S, Richter J, Giefing M, Martín-Subero JI, Siebert R. Combining array-based approaches for the identification of candidate tumor suppressor loci in mature lymphoid neoplasms. APMIS 2007;115:1107-1134.Tumor suppressor gene (TSG) inactivation by chromosomal deletions and/or mutations is a wellcharacterized genetic alteration in lymphomas. Array-based technologies have greatly increased the detection and characterization of chromosomal imbalances and regions with loss of heterozygosity (LOH), leading to the identification of a number of novel candidate TSG loci. In addition, microarray platforms for studying DNA methylation and histone modifications enable identifying epigenetic changes affecting gene expression of TSG. Combining these microarray technologies with gene expression profiling is a promising strategy to discover novel TSG in regions targeted by genetic or epigenetic alterations. In this review we present an outline of methodological aspects of the various microarray technologies, and discuss their potentials and restrictions. Furthermore, we survey research findings derived from these high-throughput techniques, which are allowing a deeper insight into the mechanisms of lymphomagenesis.