DNMT1 gene copy number does not influence susceptibility to development of malignant lymphoproliferative disease.
BACKGROUND
For many years, the methylating enzyme DNMT1 has been thought to critically influence neoplastic transformation. To determine if DNMT1 is involved in the early events of malignant transformation of lymphoid cells, we investigated whether allele-specific variation in the gene copy number of DNMT1 influences susceptibility to the development of malignant lymphoproliferative disease (LPD) associated with DNA hypermethylation.


METHODS
DNMT1 gene copy number was assessed by subjecting DNA from DNMT1A/DNMT1B heterozygous patients suffering from benign LPD or malignant LPD featuring Myf-3 hypermethylation to Southern blotting and densitometric analysis.


RESULTS
The distribution of DNMT1B to DNMT1A intensity ratios did not significantly differ between patients suffering from benign and patients suffering from malignant LPD and there was no association between increasing Myf-3 hypermethylation and increased DNMT1 gene copy number.


CONCLUSIONS
In contrast to findings in mice, the results of this study exclude a role for DNMT1 gene copy number in susceptibility to neoplastic transformation in humans.
Franchina
Maria
M
Department of Pathology, University of Western Australia, 35 Stirling Highway, Crawley, WA 6009, Australia.
Kay
Peter H
PH
D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics*; D019175:DNA Methylation; D018628:Gene Dosage; D020022:Genetic Predisposition to Disease; D006801:Humans; D008232:Lymphoproliferative Disorders / Q000201:enzymology / Q000235:genetics*; D017570:MyoD Protein / Q000235:genetics
D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human; C000619381:Dnmt1 protein, mouse