title: Mutation spectrum of RB1 gene in unilateral retinoblastoma cases from Tunisia and correlations with clinical features.
abstract: Retinoblastoma, an embryonic neoplasm of retinal origin, is the most common primary intraocular malignancy in children. Somatic inactivation of both alleles of the RB1 tumor suppressor gene in a retinal progenitor cell through diverse mechanisms including genetic and epigenetic modifications, is the crucial event in initiation of tumorigenesis in most cases of isolated unilateral retinoblastoma. We analyzed DNA from tumor tissue and from peripheral blood to determine the RB1 mutation status and seek correlations with clinical features of 37 unrelated cases of Tunisian origin with sporadic retinoblastoma. All cases were unilateral except one who presented with bilateral disease, in whom no germline coding sequence alteration was identified. A multi-step mutation scanning protocol identified bi-allelic inactivation of RB1 gene in 30 (81%) of the samples tested. A total of 7 novel mutations were identified. There were three tumors without any detectable mutation while a subset contained multiple mutations in RB1 gene. The latter group included tumors collected after treatment with chemotherapy. There were seven individuals with germline mutations and all presented with advanced stage of tumor. There was no difference in age of onset of RB based on the germline mutation status. Thus 20% of the individuals with sporadic unilateral RB in this series carried germline mutations and indicate the importance of genetic testing all children with sporadic retinoblastoma. These findings help to characterize the spectrum of mutations present in the Tunisian population and can improve genetic diagnosis of retinoblastoma.
authors.affiliation: Laboratoire de Génétique, Immunologie et Pathologies Humaines, Faculté des Sciences de Tunis, Université de Tunis EL MANAR, Campus universitaire, Tunis, 2092, Tunisia.
authors.forename: Hajer
authors.initials: H
authors.lastname: Ayari-Jeridi
authors.affiliation: Genetic Diagnostic Laboratory, Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Moran
authors.affiliation: Institut Hédi Rais d'Ophtalmologie de Tunis, Tunis, Tunisia.
authors.forename: Amel
authors.initials: A
authors.lastname: Chebbi
authors.affiliation: Institut Hédi Rais d'Ophtalmologie de Tunis, Tunis, Tunisia.
authors.forename: Hédi
authors.initials: H
authors.lastname: Bouguila
authors.affiliation: Laboratoire d'Anatomie Pathologique, Institut Salah Azaiez de Cancérologie, Tunis, Tunisia.
authors.forename: Imen
authors.initials: I
authors.lastname: Abbes
authors.affiliation: Laboratoire de Génétique, Immunologie et Pathologies Humaines, Faculté des Sciences de Tunis, Université de Tunis EL MANAR, Campus universitaire, Tunis, 2092, Tunisia.
authors.forename: Khaoula
authors.initials: K
authors.lastname: Charradi
authors.affiliation: Laboratoire de Génétique, Immunologie et Pathologies Humaines, Faculté des Sciences de Tunis, Université de Tunis EL MANAR, Campus universitaire, Tunis, 2092, Tunisia.
authors.forename: Amel
authors.initials: A
authors.lastname: Benammar-Elgaaïed
authors.affiliation: Genetic Diagnostic Laboratory, Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Arupa
authors.initials: A
authors.lastname: Ganguly
mesh_terms: D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation / Q000235:genetics; D012175:Retinoblastoma / Q000175:diagnosis* / Q000235:genetics*; D016160:Retinoblastoma Protein / Q000235:genetics*; D014416:Tunisia
chemical_list: D016160:Retinoblastoma Protein