title: Study of chromosome 9q gain, Notch pathway regulators and Tenascin-C in ependymomas.
abstract: Ependymomas are relatively uncommon tumours of the central nervous system which arise from the ependymal lining of the ventricles and spinal canal. The molecular changes leading to ependymal oncogenesis are not completely understood. We examined chromosome 9q33-34 locus for gain, potential oncogenes at this locus (Notch-1 and Tenascin-C) and Notch pathway target genes (Hes-1, Hey-2 & C-myc) in ependymomas by fluorescent in situ hybridization (FISH) and immunohistochemistry (IHC), respectively, to assess if they have any correlation with clinical characteristics. We analyzed 50 cases of ependymomas by FISH for 9q gain and by IHC for Notch-1 and its target gene proteins (Hes-1, Hey-2 and C-myc) expression. We also performed IHC for Tenascin-C to rule out any correlation with aggressiveness/grade of tumour. FISH study revealed significant chromosome 9q gain in ependymomas of adult onset (age > 18 years) and spinal cord origin. Notch-1 showed significantly more frequent immunohistochemical expression in supratentorial and anaplastic ependymomas. Tenascin-C (TN-C) expression was significant in intracranial, childhood (age ≤ 18 years) and anaplastic ependymomas. Of the three Notch pathway target gene proteins (Hes-1, Hey-2 and C-myc), Hes-1 and C-myc expression showed significant correlation with anaplastic and adult onset ependymomas, respectively. Genetic alterations are independent prognostic markers in ependymomas. A clinicopathological correlation with various molecular signatures may be helpful in the development of new therapeutic targets.
authors.affiliation: Department of Pathology, All India Institute of Medical Sciences, New Delhi, 110029, India.
authors.forename: Rakesh Kumar
authors.initials: RK
authors.lastname: Gupta
authors.forename: Mehar C
authors.initials: MC
authors.lastname: Sharma
authors.forename: Vaishali
authors.initials: V
authors.lastname: Suri
authors.forename: Aanchal
authors.initials: A
authors.lastname: Kakkar
authors.forename: Manmohan
authors.initials: M
authors.lastname: Singh
authors.forename: Chitra
authors.initials: C
authors.lastname: Sarkar
mesh_terms: D000293:Adolescent; D000328:Adult; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002899:Chromosomes, Human, Pair 9; D004806:Ependymoma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007223:Infant; D008875:Middle Aged; D051881:Receptor, Notch1 / Q000235:genetics*; D019063:Tenascin / Q000235:genetics*; D055815:Young Adult
chemical_list: C497761:NOTCH1 protein, human; D051881:Receptor, Notch1; D019063:Tenascin