Genetic and Epigenetic Profile of Retinoblastoma in a Chinese Population: Analysis of 47 Patients.

Abstract

To report genetic findings of retinoblastoma gene RB1 in a Chinese ethnic group with retinoblastoma. A retrospective noncomparative case series. Genomic DNA was extracted from peripheral blood samples, and tumor tissue samples were collected from 47 patients (37 patients with unilateral retinoblastoma). The 27 known RB1 coding exons, splicing boundaries, and promoters were screened for point mutations or small mutations by polymerase chain reaction-single-strand conformation polymorphism-DNA sequencing. Microsatellite analysis was applied to 30 patients with both blood samples and retinoblastoma tumor tissues available to examine loss of heterozygosity according to microsatellite markers within or adjacent to the RB1 locus. Methylation of the RB1 gene was investigated in retinoblastoma tissue samples of 40 patients by methylation-specific polymerase chain reaction. Mutations in the RB1 gene were identified in 10 patients (21%). A loss of heterozygosity was detected at locus D13S153 in 14 of 26 patients, at locus D13S262 in 13 of 28 patients, and at locus D13S284 in 8 of 27 patients. Altogether, loss of heterozygosity was detected in 18 (60%) of 30 patients. Loss of heterozygosity at the RB1 locus was associated with a loss of pRb expression (P = 0.01). Hypermethylation in the promoter CpG island in the RB1 gene was found in 4 (10%) of 40 examined patients. The localization and type of mutations identified in Chinese patients with retinoblastoma fit well into the pattern observed in previous studies on other ethnic groups. No new mutations were found. Future studies may examine whether these results are helpful for genetic counseling of Chinese patients.