Epigenetic alterations in disseminated neuroblastoma tumour cells: influence of TMS1 gene hypermethylation in relapse risk in NB patients.
OBJECTIVE
Most neuroblastoma patients over 18 months of age at diagnosis present disseminated disease. The presence of neuroblastoma cells in bone marrow can be used to evaluate the response to treatment. It is possible that alterations in certain tumour cells might confer a selective advantage over tumour dissemination process, and probably be helpful in the clonal selection of tumour-specific cells that could originate metastasis.


METHODS
We performed real-time quantitative PCR to identify the presence of disseminated tumour cells in bone marrow samples, and we used MSP to analyse the methylation profile of 20 genes putatively implied in dissemination.


RESULTS
We described epigenetic alterations in the methylated status of certain genes in disseminated tumour cells from bone marrow. Those cases with high rate of hypermethylation showed an increased probability of relapse during or after treatment. We found significantly poor prognosis in event-free survival in cases with hypermethylation of TMS1, MGMT and RARbeta2 genes.


CONCLUSIONS
We could not confirm the presence of a specific methylation profile in disseminated neuroblastoma tumour cells, but a high accumulation of epigenetic events in those cells is associated with a high risk of relapse, independently of MYCN amplification.
Grau
E
E
Unidad de Genética y Diagnóstico Prenatal, Edificio de Anatomia Patologica, Hospital Universitario La Fe, Av/Campanar N masculine21, 46009, Valencia, Spain. elena_grau@hotmail.com
Martinez
F
F
Orellana
C
C
Canete
A
A
Yañez
Y
Y
Oltra
S
S
Noguera
R
R
Hernandez
M
M
Bermúdez
J D
JD
Castel
V
V
D019046:Bone Marrow Neoplasms / Q000175:diagnosis / Q000235:genetics*; D053468:CARD Signaling Adaptor Proteins; D003598:Cytoskeletal Proteins / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D018572:Disease-Free Survival; D044127:Epigenesis, Genetic / Q000235:genetics*; D020869:Gene Expression Profiling; D006801:Humans; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000175:diagnosis / Q000235:genetics*; D011379:Prognosis; D012008:Recurrence; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors
D053468:CARD Signaling Adaptor Proteins; D003598:Cytoskeletal Proteins; C402202:PYCARD protein, human