Genomic analyses reveal global functional alterations that promote tumor growth and novel tumor suppressor genes in natural killer-cell malignancies
| Autor: | Wing Yan Au, Hesham H. Ali, Norio Shimizu, Liyin Shen, Javeed Iqbal, I. F L Tsui, Wing Lok Lam, Karen Dybkær, Huimin Geng, Wayne Tam, K. Patel, W. C. Chan, Ronald J. deLeeuw, David Klinkebiel, Can Küçük, Gopesh Srivastava, Judith K. Christman, Kajia Cao |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Adult
Cancer Research Tumor suppressor gene Lymphoma Biology Natural killer cell Autophagy-Related Protein 5 Gene expression PRDM1 medicine Tumor Cells Cultured Humans Genes Tumor Suppressor Gene Aged Cell Proliferation Regulation of gene expression Comparative Genomic Hybridization Gene Expression Profiling Membrane Proteins Hematology Middle Aged Crystallins Gene expression profiling Gene Expression Regulation Neoplastic Killer Cells Natural Repressor Proteins medicine.anatomical_structure Oncology Essential gene Cancer research Chromosomes Human Pair 6 Positive Regulatory Domain I-Binding Factor 1 Microtubule-Associated Proteins |
| Zdroj: | Iqbal, J, Kucuk, C, deLeeuw, R J, Srivastava, G, Tam, W, Geng, H, Klinkebiel, D, Christman, J K, Patel, K, Cao, K, Shen, L, Dybkaer, K, Tsui, I F L, Ali, H, Shimizu, N, Au, W Y, Lam, W L & Chan, W C 2009, ' Genomic analyses reveal global functional alterations that promote tumor growth and novel tumor suppressor genes in natural killer-cell malignancies ', Leukemia, vol. 23, no. 6, pp. 1139-51 . https://doi.org/10.1038/leu.2009.3 |
| ISSN: | 1476-5551 |
| Popis: | Natural killer (NK)-cell malignancies are among the most aggressive lymphoid neoplasms with very poor prognosis. We performed array comparative genomic hybridization analysis on a number of NK cell lines and primary tumors to gain better understanding of the pathogenesis and tumor biology of these malignancies. We also obtained transcriptional profiles of genes residing in these regions and compared them with normal and activated NK cells. Only 30-50% of the genes residing in the gained or deleted regions showed corresponding increased or decreased expression. However, many of the upregulated genes in regions of gain are functionally important for the proliferation and growth of the neoplastic population. Genes downregulated in regions of loss included many transcription factors or repressors, tumor suppressors or negative regulators of the cell cycle. The minimal common region of deletion in 6q21 included three known genes (PRDM1, ATG5 and AIM1) showing generally low expression. Mutations resulting in truncated PRDM1 and changes in conserved amino-acid sequences of AIM1 were detected. Highly methylated CpG islands 5' of PRDM1 and AIM1 correlated with low expression of the transcripts. Reversal of methylation by Decitabine induced expression of PRDM1 and cell death. In conclusion, we have shown a general tumor-promoting effect of genetic alterations and have identified PRDM1 as the most likely target gene in del6q21. ATG5, an essential gene for autophagy and AIM1, a gene implicated in melanoma, may also participate in the functional abnormalities. Leukemia (2009) 23, 1139-1151; doi: 10.1038/leu.2009.3; published online 5 February 2009 |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|