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Methylation of tumor‐suppressor genes in neuroblastoma: The RASSF1A gene is almost always methylated in primary tumors
Author(s) -
Michalowski Mariana Bohns,
de Fraipont Florence,
Plantaz Dominique,
Michelland Sylvie,
Combaret Valérie,
Favrot MarieChristine
Publication year - 2008
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.21279
Subject(s) - fhit , epigenetics , dna methylation , methylation , medicine , cancer research , neuroblastoma , suppressor , gene , tumor suppressor gene , cancer , disease , oncology , carcinogenesis , biology , gene expression , genetics , cell culture
Background Currently, the best characterized genetic aberration in neuroblastoma (NB) is MYCN amplification, which has been clearly related to prognosis. In the present study, we investigated whether specific epigenetic alterations are associated with stage of disease. Procedure Sixty‐two NBs (45 primary tumors and 17 NBs at relapse) were studied in terms of the methylation status of 19 genes (p15INK4a, p16INK4a, p14ARF, APC, RB1, RASSF1A, BLU, FHIT, RARβ, INI1, TIMP3, NF2, MGMT, DAPK, FLIP, ECAD, CASP8, and the receptors DcR1 and DcR2). Results At diagnosis, we found hypermethylation of RASSF1A in 93% of these tumors, hypermethylation of TIMP3 in 51%, of CASP8 in 38%, of BLU in 34%, of DcR2 in 25%, and of DcR1 in 11%. All 17 tumors tested at relapse showed hypermethylation of RASSF1A (100%), while 10 showed hypermethylation of TIMP3 (59%), six of CASP8 (35%), five of DcR2 (29%), four of BLU (24%), and three of DcR1 (18%). Hypermethylation was related to clinical stage; NBs at stages 1, 2, and 4s were less frequently methylated than stages 3 and 4 disease ( P = 0.002). Conclusion These results from our series indicate that hypermethylation of tumor‐suppressor genes may be important in the development and evolution of NB. These epigenetic alterations could be used as a marker of the disease and genes regulating methylation should be considered as possible therapeutic targets in NB. Pediatr Blood Cancer 2008;50:29–32. © 2007 Wiley‐Liss, Inc.