1 . 2 . Three - hit hypothesis in astrocytoma Parvin Mehdipour

Astrocytoma as a primary tumour is the core item in this section in which, by considering a pedigree-based research approach, the involvement of Ataxia-Telangiectasia (AT) gene is investigated. The two-hit -hypothesis of Knudson’s model is given to clarify the process of tumourigenesis in retinoblastoma. Lack of any available data for any hit hypothesis in brain tumours was the reason why the three-hit hypothesis in astrocytoma was formulated and included in this section. ATM alterations were reported in medulloblastomas, gliomas, but not in astrocytoma. The polymorphism D1853N was only reported in healthy individuals and medulloblastomas. This polymorphism was detected in a 28 year-old femaleproband affected with astrocytoma. As the triangle initiator of the three-hit hypothesis, D1853N is the first germ line hit, IVS 3863T→A is the second hit, and IVS3830 A→G is the third hit. In addition, the D1853N polymorphism was on a different allele than from IVS 3863T→A and IVS 3830 A→G. However, these three triggers could be considered as triangle initiators for the course of evolution in astrocytoma. However, the present data could highlight the crucial role of specific intronic region of the ATM gene involved in cancer and also the importance of pedigree analysis. This polymorphism might be useful as a marker in astrocytoma. Correspondence/Reprint request: Professor Dr. Parvin Mehdipour, Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, P.O.Box 14155-6447, Zip code 14176-13151, Tehran Iran. E-mail: [email protected]