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.
