Identification of candidate tumour suppressor gene loci for Hodgkin and Reed-Sternberg cells by characterisation of homozygous deletions in classical Hodgkin lymphoma cell lines.
Several 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.
Giefing
Maciej
M
Institute of Human Genetics, University Hospital Schleswig-Holstein, Campus Kiel, Christian-Albrechts-University Kiel, 24105 Kiel, Germany. giefingm@man.poznan.pl
Arnemann
Joachim
J
Martin-Subero
Jose Ignacio
JI
Nieländer
Inga
I
Bug
Stefanie
S
Hartmann
Sylvia
S
Arnold
Norbert
N
Tiacci
Enrico
E
Frank
Matthias
M
Hansmann
Martin-Leo
ML
Küppers
Ralf
R
Siebert
Reiner
R
D017209:Apoptosis / Q000235:genetics; D016923:Cell Death / Q000235:genetics; D055028:Comparative Genomic Hybridization / Q000379:methods; D017353:Gene Deletion; D015870:Gene Expression; D020869:Gene Expression Profiling / Q000379:methods; D016147:Genes, Tumor Suppressor; D006689:Hodgkin Disease / Q000235:genetics* / Q000473:pathology; D006720:Homozygote; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D016133:Polymerase Chain Reaction / Q000379:methods; D016539:Reed-Sternberg Cells / Q000473:pathology*; D014407:Tumor Cells, Cultured