Linked Life Data

15327516

Source:http://linkedlifedata.com/resource/pubmed/id/15327516

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2004-8-25
pubmed:abstractText
We investigated the prevalence and prognostic role of CpG island methylation of the reduced folate carrier (RFC) gene promoter region in primary central nervous system lymphoma (PCNSL) in immunocompetent patients. Genomic DNA from 40 PCNSL was used for methylation-specific polymerase chain reaction and bisulphite genomic sequencing of the RFC promoter region. Human immunodeficiency virus-negative systemic diffuse large B-cell lymphomas (DLBCL) were used as controls (n = 50). The impact on outcome of RFC promoter methylation was assessed in 37 PCNSL patients treated with high-dose methotrexate (HD-MTX)-based chemotherapy +/- radiotherapy. RFC promoter methylation occurred in 12 of 40 (30%) PCNSL and in four of 50 (8%) DLBCL (P = 0.01). Of 37 PCNSL treated with HD-MTX-based chemotherapy, methylation occurred in nine cases (24%, M-PCNSL), while 28 cases (76%, U-PCNSL) were negative. Three M-PCNSL (33%) and 15 U-PCNSL (54%) achieved complete remission (CR) after primary chemotherapy. Logistic regression confirmed the independent association between CR rate and International Extranodal Lymphoma Study Group score (P = 0.03), RFC promoter methylation (P = 0.07) and use of cytarabine (P = 0.08). The 3-year failure-free survival (FFS) and overall survival for M-PCNSL and U-PCNSL was 0% vs. 31 +/- 9% (P = 0.34) and 0% vs. 31 +/- 9% (P = 0.35) respectively. This is the first study to assess the methylation status of the RFC promoter in human tumour samples. RFC methylation is more common in PCNSL compared with systemic DLBCL, and is associated with a lower CR rate to HD-MTX-based chemotherapy. If confirmed in prospective trials on PCNSL treated with HD-MTX alone, these data may suggest the necessity for alternative strategies in M-PCNSL considering the increased risk of MTX resistance by tumour cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0007-1048
pubmed:author
pubmed:issnType
Print
pubmed:volume
126
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
657-64
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:15327516-Adult, pubmed-meshheading:15327516-Aged, pubmed-meshheading:15327516-Antineoplastic Agents, pubmed-meshheading:15327516-Central Nervous System Neoplasms, pubmed-meshheading:15327516-CpG Islands, pubmed-meshheading:15327516-Drug Resistance, Neoplasm, pubmed-meshheading:15327516-Female, pubmed-meshheading:15327516-Humans, pubmed-meshheading:15327516-Lymphoma, Large B-Cell, Diffuse, pubmed-meshheading:15327516-Male, pubmed-meshheading:15327516-Membrane Transport Proteins, pubmed-meshheading:15327516-Methotrexate, pubmed-meshheading:15327516-Methylation, pubmed-meshheading:15327516-Middle Aged, pubmed-meshheading:15327516-Predictive Value of Tests, pubmed-meshheading:15327516-Prevalence, pubmed-meshheading:15327516-Reduced Folate Carrier Protein, pubmed-meshheading:15327516-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:15327516-Sequence Analysis, DNA
pubmed:year
2004
pubmed:articleTitle
Aberrant methylation in the promoter region of the reduced folate carrier gene is a potential mechanism of resistance to methotrexate in primary central nervous system lymphomas.
pubmed:affiliation
Department of Radiochemotherapy, San Raffaele H Scientific Institute, via Olgettina 60, 20132 Milan, Italy. andres.ferrari@hsr.it
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't