title: Constitutional and somatic RB1 mutation spectrum in nonfamilial unilateral and bilateral retinoblastoma in India.
abstract: An epidemiologic survey has indicated a comparatively high prevalence of retinoblastoma (Rb) in Asian countries. Recently, the development of preventive strategies in nonfamilial Rb has become a major goal. The present studies were designed for identification and characterization of constitutional and somatic RB1 gene mutations by conventional cytogenetics, fluorescent in situ hybridization (FISH) and polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP)-DNA sequencing. Of 34 patients 32 were nonfamilial and 2 were familial Rb. Maternal inheritance of del (13q14) was common. FISH was sensitive in detecting monoallelic RB1 deletion/deletion mosaicism as a first genetic hit in 20% of cases. Somatic and germline RB1 point mutations affected exons 3, 17, 20, and 21 and these were identified as novel mutations. Involvement of exon 20 as a predisposing mutation in sporadic unilateral retinoblastoma (URB) probably suggests the susceptibility of exon 20 to unknown etiologic factors in our population. A de novo RB1 deletion along with transmitted RB1 point mutation from an asymptomatic parent was identified as a unique predisposing RB1 mutation chimerism in a URB case that later evolved to bilateral retinoblastoma (BRB). The predisposing mutations such as del (13q), RB1 mono-allelic deletion and RB1 point mutation in sporadic Rb were de novo as well as transmitted mutations from asymptomatic/symptomatic parents. The RB1 mutation incidence was comparatively higher (25%) in nonfamilial Rb with emphasis on high prevalence in sporadic URB (18% versus 0%-9% in the literature series). The present studies demonstrated the efficacy of a multitechnique approach to detect various types of constitutional RB1 mutations such as RB1 deletion, deletion mosaicism, point mutation, mutation chimerism in patients of symptomatic/asymptomatic parents.
authors.affiliation: Cancer Cytogenetics Laboratory, Tata Memorial Hospital, Parel, Mumbai, India.
authors.forename: M N
authors.initials: MN
authors.lastname: Bamne
authors.forename: P N
authors.initials: PN
authors.lastname: Ghule
authors.forename: J
authors.initials: J
authors.lastname: Jose
authors.forename: S D
authors.initials: SD
authors.lastname: Banavali
authors.forename: P A
authors.initials: PA
authors.lastname: Kurkure
authors.forename: P S
authors.initials: PS
authors.lastname: Amare Kadam
mesh_terms: D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D017931:DNA Primers; D005260:Female; D017353:Gene Deletion; D016161:Genes, Retinoblastoma; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007194:India; D007223:Infant; D008297:Male; D009154:Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D012175:Retinoblastoma / Q000235:genetics*
chemical_list: D017931:DNA Primers