Tumor Biology

, Volume 36, Issue 4, pp 2383–2391 | Cite as

Epigenetic regulation of human hedgehog interacting protein in glioma cell lines and primary tumor samples

  • Mehdi H. Shahi
  • Idoya Zazpe
  • Mohammad Afzal
  • Subrata Sinha
  • Robert B. Rebhun
  • Bárbara Meléndez
  • Juan A. Rey
  • Javier S. Castresana
Research Article


Glioma constitutes one of the most common groups of brain tumors, and its prognosis is influenced by different genetic and epigenetic modulations. In this study, we demonstrated low or no expression of hedgehog interacting protein (HHIP) in most of the cell lines and primary glioma tumor samples. We further proceeded to promoter methylation study of this gene in the same cell lines and primary tumor samples and found 87 % (7/8) HHIP methylation in glioblastoma cell lines and 75 % (33/44) in primary tumor samples. These methylation pattern correlates with low or unexpressed HHIP in both cell lines and primary tumor samples. Our results suggest the possibility of epigenetic regulation of this gene in glioma, similarly to medulloblastoma, gastric, hepatic, and pancreatic cancers. Also, HHIP might be a diagnostic or prognostic marker in glioma and help to the detection of these tumors in early stages of disease.


Human hedgehog interacting protein (HHIP) Glioma Glioblastoma promoter methylation Melting curve analysis-Meth (MCA-Meth) GLI1 



M.H. Shahi was a fellow of AECI (Agencia Española de Cooperación Internacional), Madrid, Spain. This research was supported in part by grants from the Departamento de Salud del Gobierno de Navarra, Caja Navarra (project 13912), Fundación Universitaria de Navarra, Pamplona, and Fondo de Investigación Sanitaria (PI-081849, to JSC and PI13/00055, to JAR), Madrid.


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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Mehdi H. Shahi
    • 1
    • 9
  • Idoya Zazpe
    • 2
  • Mohammad Afzal
    • 3
  • Subrata Sinha
    • 4
  • Robert B. Rebhun
    • 5
  • Bárbara Meléndez
    • 6
  • Juan A. Rey
    • 7
  • Javier S. Castresana
    • 1
    • 8
  1. 1.Brain Tumor Biology UnitUniversity of Navarra School of SciencesPamplonaSpain
  2. 2.Neurosurgery ServiceHospital of NavarraPamplonaSpain
  3. 3.Department of ZoologyAligarh Muslim UniversityAligarhIndia
  4. 4.National Brain Research CentreGurgaonIndia
  5. 5.Department of Surgical and Radiological SciencesUniversity of California Davis School of Veterinary MedicineDavisUSA
  6. 6.Molecular Pathology Research Unit, Department of PathologyVirgen de la Salud HospitalToledoSpain
  7. 7.IdiPaz Research UnitLa Paz University HospitalMadridSpain
  8. 8.Department of Biochemistry and GeneticsUniversity of Navarra School of SciencesPamplonaSpain
  9. 9.Interdisciplinary Brain Research Centre, Faculty of MedicineAligarh Muslim UniversityAligarhIndia

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