Loss of heterozygosity and microsatellite instability on chromosome arm 10q in neuroblastoma.
Tumor suppressor genes can be inactivated by various mechanisms, including promoter hypermethylation and loss of heterozygosity. We screened the 10q locus for loss of heterozygosity and the promoter methylation status of PTEN, MGMT, MXI1, and FGFR2 in neuroblastic tumors and neuroblastoma cell lines. Expression of these genes in cell lines was analyzed with reverse transcriptase-polymerase chain reaction. Loss of heterozygosity at 10q was detected in 18% of tumors and microsatellite instability in 14%. Promoter hypermethylation of MGMT appeared in 8% of tumors and 25% of cell lines. Correlation between methylation status and lack of expression was evident for PTEN, FGFR2, and MXI1 and was less clear for MGMT. No associations between these alterations and MYCN amplification, 1p deletion, or aggressive tumor histology could be demonstrated, singly or in combination. These data suggest that 10q alterations might be implicated in the development of a small number of neuroblastomas.
Lázcoz
Paula
P
Department of Health Sciences, Public University of Navarra, 31006 Pamplona, Spain.
Muñoz
Jorge
J
Nistal
Manuel
M
Pestaña
Angel
A
Encío
Ignacio J
IJ
Castresana
Javier S
JS
D045744:Cell Line, Tumor; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D019175:DNA Methylation; D015254:DNA Modification Methylases; D045643:DNA Repair Enzymes; D005819:Genetic Markers; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics*; D053842:Microsatellite Instability; D009447:Neuroblastoma / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025803:Tumor Suppressor Protein p14ARF / Q000235:genetics; D025521:Tumor Suppressor Proteins
D005819:Genetic Markers; D025803:Tumor Suppressor Protein p14ARF; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes