4q loss is potentially an important genetic event in MM tumorigenesis: identification of a tumor suppressor gene regulated by promoter methylation at 4q13.3, platelet factor 4
| Autor: | Jian Hou, J. C. W. Chan, Wai Shan Wong, Suk Hang Cheng, Kin-Mang Lau, Margaret H.L. Ng, Hua Jiang, Raymond W. Chu, Natalie P. H. Chan, Ho Keung Ng, Kwok Wai Lo, Angela B.Y. Hui, Herman S.Y. Liu |
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| Rok vydání: | 2006 |
| Předmět: |
Male
Transcription Genetic Tumor suppressor gene Immunology In situ hybridization Biology Platelet Factor 4 medicine.disease_cause Biochemistry Cell Line Tumor medicine Humans RNA Messenger Promoter Regions Genetic Alleles In Situ Hybridization Aged Aged 80 and over Regulation of gene expression Chromosomes Human Pair 13 medicine.diagnostic_test Tumor Suppressor Proteins Cell Biology Hematology DNA Methylation Middle Aged medicine.disease Molecular biology Gene Expression Regulation Neoplastic Cell Transformation Neoplastic DNA methylation Disease Progression Cancer research Female Chromosomes Human Pair 4 Multiple Myeloma Carcinogenesis Gene Deletion Monoclonal gammopathy of undetermined significance Comparative genomic hybridization Fluorescence in situ hybridization |
| Zdroj: | Blood. 109:2089-2099 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood-2006-04-018770 |
| Popis: | In this study, we have elucidated the chromosomal imbalances in the multistep pathogenesis and delineated several critical tumor suppressor gene (TSG) loci in multiple myeloma (MM). By using comparative genomic hybridization, allelotyping, and multicolor interphase fluorescence in situ hybridization, 5 MM cell lines and bone marrow CD138+ plasma cells from 88 Chinese patients with monoclonal gammopathy of undetermined significance (MGUS) and early and advanced stages of MM were investigated. In all MGUS and MM samples, chromosome copy number abnormalities were detected. A higher number of chromosomal imbalances and specific genetic alterations are involved in MGUS to MM transition (−6q, +3p, and +1p) and MM progression (+2p and +9q). In addition to −13q, we first found high frequencies (42% to 46%) of −4q involving high percentages (70% to 74%) of clonal plasma cells in both MGUS and MM, suggesting that inactivation of TSG in this region is also a potentially critical genetic event in MM tumorigenesis. By high-resolution allelotyping, we defined a common deletion region on 4q13.3 and found that a candidate TSG, platelet factor 4, was frequently silenced by promoter hypermethylation in MM (15 of 28) and MM cell lines (5 of 5). These data have opened up a new approach in the molecular targeting therapy and provide novel insights into MM tumorigenesis. |
| Databáze: | OpenAIRE |
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