Source:http://linkedlifedata.com/resource/pubmed/id/19531770
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
8
|
| pubmed:dateCreated |
2009-7-30
|
| pubmed:abstractText |
Multiple myeloma (MM) is characterized by a wide spectrum of genetic changes. Global hypomethylation of repetitive genomic sequences such as long interspersed nuclear element 1 (LINE-1), Alu and satellite alpha (SAT-alpha) sequences has been associated with chromosomal instability in cancer. Methylation status of repetitive elements in MM has never been investigated. In the present study, we used a quantitative bisulfite-polymerase chain reaction pyrosequencing method to evaluate the methylation patterns of LINE-1, Alu and SAT-alpha in 23 human myeloma cell lines (HMCLs) and purified bone marrow plasma cells from 53 newly diagnosed MM patients representative of different molecular subtypes, 7 plasma cell leukemias (PCLs) and 11 healthy controls. MMs showed a decrease of Alu [median: 21.1 %5-methylated cytosine (%5mC)], LINE-1 (70.0%5mC) and SAT-alpha (77.9%5mC) methylation levels compared with controls (25.2, 79.5and 89.5%5mC, respectively). Methylation levels were lower in PCLs and HMCLs compared with MMs (16.7 and 14.8%5mC for Alu, 45.5 and 42.4%5mC for LINE-1 and 33.3 and 43.3%5mC for SAT-alpha, respectively). Notably, LINE-1 and SAT-alpha methylation was significantly lower in the non-hyperdiploid versus hyperdiploid MMs (P = 0.01 and 0.02, respectively), whereas Alu and SAT-alpha methylation was significantly lower in MMs with t(4;14) (P = 0.02 and 0.004, respectively). Finally, we correlated methylation patterns with DNA methyltransferases (DNMTs) messenger RNA levels showing in particular a progressive and significant increase of DNMT1 expression from controls to MMs, PCLs and HMCLs (P < 0.001). Our results indicate that global hypomethylation of repetitive elements is significantly associated with tumor progression in MM and may contribute toward a more extensive stratification of the disease.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Aug
|
| pubmed:issn |
1460-2180
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| pubmed:author |
pubmed-author:BaccarelliAndreaA,
pubmed-author:BertazziPier AlbertoPA,
pubmed-author:BollatiValentinaV,
pubmed-author:DeliliersGiorgio LambertenghiGL,
pubmed-author:FabrisSoniaS,
pubmed-author:MoscaLauraL,
pubmed-author:MottaValeriaV,
pubmed-author:NeriAntoninoA,
pubmed-author:PegoraroValeriaV,
pubmed-author:RonchettiDomenicaD
|
| pubmed:issnType |
Electronic
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| pubmed:volume |
30
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
1330-5
|
| pubmed:meshHeading |
pubmed-meshheading:19531770-Adult,
pubmed-meshheading:19531770-Aged,
pubmed-meshheading:19531770-Aged, 80 and over,
pubmed-meshheading:19531770-Alu Elements,
pubmed-meshheading:19531770-Chromosome Aberrations,
pubmed-meshheading:19531770-CpG Islands,
pubmed-meshheading:19531770-DNA, Neoplasm,
pubmed-meshheading:19531770-DNA, Satellite,
pubmed-meshheading:19531770-DNA (Cytosine-5-)-Methyltransferase,
pubmed-meshheading:19531770-DNA Methylation,
pubmed-meshheading:19531770-Female,
pubmed-meshheading:19531770-Humans,
pubmed-meshheading:19531770-Leukemia, Plasma Cell,
pubmed-meshheading:19531770-Long Interspersed Nucleotide Elements,
pubmed-meshheading:19531770-Male,
pubmed-meshheading:19531770-Middle Aged,
pubmed-meshheading:19531770-Multiple Myeloma,
pubmed-meshheading:19531770-Repetitive Sequences, Nucleic Acid,
pubmed-meshheading:19531770-Tumor Cells, Cultured
|
| pubmed:year |
2009
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| pubmed:articleTitle |
Differential repetitive DNA methylation in multiple myeloma molecular subgroups.
|
| pubmed:affiliation |
Center of Molecular and Genetic Epidemiology, EPOCA, Epidemiology Research Center, Università degli Studi di Milano and Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, 20122 Milan, Italy.
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|