Loss of 5hmC identifies a new type of aberrant DNA hypermethylation in glioma
Por:
Fernandez, AF, Bayon, GF, Sierra, MI, Urdinguio, RG, Torano, E, Garcia, MG, Carella, A, Lopez, V, Santamarina, P, Perez, RF, Belmonte, T, Tejedor, JR, Cobo, I, Menendez, P, Mangas, C, Ferrero, C, Rodrigo, L, Astudillo, A, Ortea, I, Diaz, SC, Rodriguez-Gonzalez, P, Alonso, JIG, Mollejo, M, Melendez, B, Dominguez, G, Bonilla, F and Fraga, MF
Publicada:
1 sep 2018
Resumen:
Aberrant DNA hypermethylation is a hallmark of cancer although the underlying molecular mechanisms are still poorly understood. To study the possible role of 5-hydroxymethylcytosine (5hmC) in this process we analyzed the global and locus-specific genome-wide levels of 5hmC and 5-methylcytosine (5mC) in human primary samples from 12 non-tumoral brains and 53 gliomas. We found that the levels of 5hmC identified in non-tumoral samples were significantly reduced in gliomas. Strikingly, hypo-hydroxymethylation at 4627 (9.3%) CpG sites was associated with aberrant DNA hypermethylation and was strongly enriched in CpG island shores. The DNA regions containing these CpG sites were enriched in H3K4me2 and presented a different genuine chromatin signature to that characteristic of the genes classically aberrantly hypermethylated in cancer. As this 5mC gain is inversely correlated with loss of 5hmC and has not been identified with classical sodium bisulfite-based technologies, we conclude that our data identifies a novel 5hmC-dependent type of aberrant DNA hypermethylation in glioma.
Filiaciones:
Fernandez, AF:
Univ Oviedo, Inst Oncol Asturias IUOPA, ISPA HUCA, Principado Asturias, Oviedo, Spain
Bayon, GF:
Univ Oviedo, Inst Oncol Asturias IUOPA, ISPA HUCA, Principado Asturias, Oviedo, Spain
Sierra, MI:
Univ Oviedo, Inst Oncol Asturias IUOPA, ISPA HUCA, Principado Asturias, Oviedo, Spain
Urdinguio, RG:
Univ Oviedo, Nanomat & Nanotechnol Res Ctr CINN CSIC, Principado Asturias, Oviedo, Spain
Torano, E:
Univ Oviedo, Inst Oncol Asturias IUOPA, ISPA HUCA, Principado Asturias, Oviedo, Spain
Univ Oviedo, Nanomat & Nanotechnol Res Ctr CINN CSIC, Principado Asturias, Oviedo, Spain
Garcia, MG:
Univ Oviedo, Inst Oncol Asturias IUOPA, ISPA HUCA, Principado Asturias, Oviedo, Spain
Univ Oviedo, Nanomat & Nanotechnol Res Ctr CINN CSIC, Principado Asturias, Oviedo, Spain
Carella, A:
Univ Oviedo, Inst Oncol Asturias IUOPA, ISPA HUCA, Principado Asturias, Oviedo, Spain
Univ Oviedo, Nanomat & Nanotechnol Res Ctr CINN CSIC, Principado Asturias, Oviedo, Spain
Lopez, V:
Univ Oviedo, Nanomat & Nanotechnol Res Ctr CINN CSIC, Principado Asturias, Oviedo, Spain
Santamarina, P:
Univ Oviedo, Inst Oncol Asturias IUOPA, ISPA HUCA, Principado Asturias, Oviedo, Spain
Univ Oviedo, Nanomat & Nanotechnol Res Ctr CINN CSIC, Principado Asturias, Oviedo, Spain
Perez, RF:
Univ Oviedo, Inst Oncol Asturias IUOPA, ISPA HUCA, Principado Asturias, Oviedo, Spain
Univ Oviedo, Nanomat & Nanotechnol Res Ctr CINN CSIC, Principado Asturias, Oviedo, Spain
Belmonte, T:
Univ Oviedo, Inst Oncol Asturias IUOPA, ISPA HUCA, Principado Asturias, Oviedo, Spain
Univ Oviedo, Nanomat & Nanotechnol Res Ctr CINN CSIC, Principado Asturias, Oviedo, Spain
Tejedor, JR:
Univ Oviedo, Inst Oncol Asturias IUOPA, ISPA HUCA, Principado Asturias, Oviedo, Spain
Cobo, I:
Univ Oviedo, Inst Oncol Asturias IUOPA, ISPA HUCA, Principado Asturias, Oviedo, Spain
Univ Barcelona, Josep Carreras Leukemia Res Inst, Sch Med, Dept Biomed, Barcelona, Spain
:
Univ Barcelona, Josep Carreras Leukemia Res Inst, Sch Med, Dept Biomed, Barcelona, Spain
ISCIII, Inst Catalana Recerca & Estudis Avancats ICREA, Ctr Invest Biomed Red Canc CIBER ONC, Barcelona, Spain
Mangas, C:
Univ Oviedo, Inst Oncol Asturias IUOPA, ISPA HUCA, Principado Asturias, Oviedo, Spain
Ferrero, C:
Univ Oviedo, Inst Oncol Asturias IUOPA, ISPA HUCA, Principado Asturias, Oviedo, Spain
Rodrigo, L:
Hosp Univ Cent Asturias, Inst Univ Oncol Principado Asturias, Dept Gastroenterol, Oviedo, Spain
Astudillo, A:
Hosp Univ Cent Asturias, Inst Univ Oncol Principado Asturias, Dept Pathol, Oviedo, Spain
Ortea, I:
Maimonides Inst Biomed Res, Prote Unit, IMIBIC, Cordoba, Spain
Diaz, SC:
Univ Oviedo, Mass Spectrometry Unit, Oviedo, Spain
Rodriguez-Gonzalez, P:
Univ Oviedo, Dept Phys & Analyt Chem, Oviedo, Spain
Alonso, JIG:
Univ Oviedo, Dept Phys & Analyt Chem, Oviedo, Spain
Mollejo, M:
Hosp Virgen de la Salud, Dept Pathol, Avd Barber 30, Toledo 45005, Spain
Melendez, B:
Hosp Virgen de la Salud, Dept Pathol, Avd Barber 30, Toledo 45005, Spain
Dominguez, G:
Univ Autonoma Barcelona, Med Oncol Serv, Fac Med, Hosp Univ Puerta de Hierro Majadahonda, Madrid, Spain
Bonilla, F:
Univ Autonoma Barcelona, Med Oncol Serv, Fac Med, Hosp Univ Puerta de Hierro Majadahonda, Madrid, Spain
Fraga, MF:
Univ Oviedo, Nanomat & Nanotechnol Res Ctr CINN CSIC, Principado Asturias, Oviedo, Spain
Bronze, Green Submitted
|