Loading…
Promoter methylation of RASSF1A, RARβ and DAPK predict poor prognosis of patients with malignant mesothelioma
Hypermethylation occurs frequently in neoplastic cells and affects tumorigenesis. Malignant mesothelioma is an aggressive cancer developing in the thoracic cavity and patients have a rather bad prognosis. Our goal was to determine epigenetic alterations of a series of genes and to analyse the potent...
Saved in:
Published in: | Lung cancer (Amsterdam, Netherlands) Netherlands), 2006-10, Vol.54 (1), p.109-116 |
---|---|
Main Authors: | , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
Summary: | Hypermethylation occurs frequently in neoplastic cells and affects tumorigenesis. Malignant mesothelioma is an aggressive cancer developing in the thoracic cavity and patients have a rather bad prognosis. Our goal was to determine epigenetic alterations of a series of genes and to analyse the potential correlation of such changes with overall survival. We have analysed the methylation status of the promoter region of nine genes in serum DNA of mesothelioma patients by a nested methylation-specific PCR. Modest methylation frequencies were detected for
APC1A (14.3%),
RASSF1A (19.5%) and
DAPK (20.0%) while hypermethylation of
E-
cadherin (71.4%) and
FHIT (78.0%) occurred at a high incidence. Intermediate values were seen for
p16
INK4a
(28.2%),
APC1B (32.5%),
p14
ARF
(44.2%) and
RARβ (55.8%). The methylation status of none of the single genes significantly influenced prognosis. In contrast, combining
RARβ with either
DAPK or
RASSF1A showed a significantly shorter overall survival of those patients who had both genes methylated compared to those with only one or no epigenetic alteration (
P
=
0.025 and 0.040, respectively). Similarly, the combination of all three genes revealed a worse prognosis for patients with double or triple methylations compared to the group which had only one or no gene methylated (
P
=
0.028). Our results support the idea that the prognostic value of a combination of epigenetic alterations is superior to the impact of an individual gene alone on overall survival. |
---|---|
ISSN: | 0169-5002 1872-8332 |
DOI: | 10.1016/j.lungcan.2006.06.017 |