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, RARbeta, 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. (c) 2007 Wiley-Liss, Inc.
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, RARbeta, 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. (c) 2007 Wiley-Liss, Inc.
Authors: Gemma Mayol; José I Martín-Subero; José Ríos; Ana Queiros; Marta Kulis; Mariona Suñol; Manel Esteller; Soledad Gómez; Idoia Garcia; Carmen de Torres; Eva Rodríguez; Patricia Galván; Jaume Mora; Cinzia Lavarino Journal: PLoS One Date: 2012-11-07 Impact factor: 3.240
Authors: Anneleen Decock; Maté Ongenaert; Jasmien Hoebeeck; Katleen De Preter; Gert Van Peer; Wim Van Criekinge; Ruth Ladenstein; Johannes H Schulte; Rosa Noguera; Raymond L Stallings; An Van Damme; Geneviève Laureys; Joëlle Vermeulen; Tom Van Maerken; Frank Speleman; Jo Vandesompele Journal: Genome Biol Date: 2012-10-03 Impact factor: 13.583
Authors: Jennifer Law; Mohamed Salla; Alaa Zare; Yoke Wong; Le Luong; Natalia Volodko; Orysya Svystun; Kayla Flood; Jonathan Lim; Miranda Sung; Jason R B Dyck; Chong Teik Tan; Yu-Chin Su; Victor C Yu; John Mackey; Shairaz Baksh Journal: J Biol Chem Date: 2015-08-12 Impact factor: 5.157