Back to Search
Start Over
Alteration of enhancer of polycomb 1 at 10p11.2 is one of the genetic events leading to development of adult T-cell leukemia/lymphoma.
- Source :
-
Genes, chromosomes & cancer [Genes Chromosomes Cancer] 2009 Sep; Vol. 48 (9), pp. 768-76. - Publication Year :
- 2009
-
Abstract
- Adult T-cell leukemia/lymphoma (ATLL) is a malignant tumor caused by latent human T-lymphotropic virus 1 (HTLV-1) infection. We previously identified a common breakpoint cluster region at 10p11.2 in acute-type ATLL by spectral karyotyping. Single nucleotide polymorphism array comparative genomic hybridization analysis of the breakpoint region in three ATLL-related cell lines and four patient samples revealed that the chromosomal breakpoints are localized within the enhancer of polycomb 1 (EPC1) gene locus in an ATLL-derived cell line (SO4) and in one patient with acute-type ATLL. EPC1 is a human homologue of the E(Pc) enhancer of polycomb gene of Drosophila. Inappropriate expression of the polycomb group gene family has been linked to the loss of normal gene silencing pathways, which can contribute to the loss of cell identity and malignant transformation in many kinds of cancers. In the case of the SO4 cell line, which carried a der(10)t(2;10)(p23;p11.2) translocation, EPC1 was fused with the additional sex combs-like 2 (ASXL2) gene at 2p23.3 (EPC1/ASXL2). In the case with an acute-type ATLL, who carried a der(10)del(10)(p11.2)del(10)(q22q24) translocation, a putative truncated EPC1 gene (EPC1tr) was identified. Overexpression of EPC1/ASXL2 enhanced cell growth in T-leukemia cells, and a GAL4-EPC1/ASXL2 fusion protein showed high transcriptional activity. Although a GAL4-EPC1tr fusion protein did not activate transcription, overexpression of EPC1tr accelerated cell growth in leukemia cells, suggesting that the EPC1 structural abnormalities in the SO4 cell line and in the patient with acute-type ATLL may contribute to leukemogenesis.
- Subjects :
- Adult
CD4-Positive T-Lymphocytes
Cell Line, Tumor
Cell Proliferation
Cells, Cultured
Chromosomal Proteins, Non-Histone metabolism
Chromosome Breakage
Comparative Genomic Hybridization
Gene Expression Regulation, Neoplastic
Humans
Leukemia-Lymphoma, Adult T-Cell metabolism
Mutant Chimeric Proteins genetics
Mutant Chimeric Proteins metabolism
Oligonucleotide Array Sequence Analysis
Repressor Proteins metabolism
Transcription, Genetic
Translocation, Genetic
Chromosomal Proteins, Non-Histone genetics
Chromosomes, Human, Pair 10
Leukemia-Lymphoma, Adult T-Cell genetics
Repressor Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1098-2264
- Volume :
- 48
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Genes, chromosomes & cancer
- Publication Type :
- Academic Journal
- Accession number :
- 19484761
- Full Text :
- https://doi.org/10.1002/gcc.20681