Genetic alterations on chromosome 19, 20, 21, 22, and X detected by loss of heterozygosity analysis in retinoblastoma.
OBJECTIVE
To explore the presence of common genetic alterations in retinoblastoma and to localize the altered genomic regions.


METHODS
Genetic analysis included determinations of the loss of heterozygosity (LOH) and microsatellite instability (MSI) on chromosomes 19, 20, 21, 22, and X. Investigations were carried out among 15 microdissected retinoblastoma tumors and corresponding genomic DNA specimens.


RESULTS
Among the 15 retinoblastoma cases, 73% (11/15) showed genome instability (LOH and/or MSI) at one or more loci on the 5 chromosomes, although loci with recurrent LOH was infrequent. The loss of a single allele was more frequent in chromosomes 19 (33%) and 20 (27%) than the other 3 chromosomes. Five loci with recurrent allelic loss were identified, among them the most frequent allelic losses were between D19S902 and D19S571 on 19q13 and were identified in 3 out of the 15 tumor specimens. The results suggested that gene loci in the 19q13 region may be associated with tumor development in retina. In addition, 3 specimens showed moderate frequency of LOH and/or MSI in more than 6 microsatellite markers, indicating genomic instability to occur at least in a subset of retinoblastoma.


CONCLUSIONS
Our results provide the first evidence of LOH in chromosomes 19 and 20 in retinoblastoma. They also support the proposition that presence of genome instability in retinoblastoma may play a role in the tumorigenesis or progression of retinoblastoma.
Huang
Qing
Q
Department of Ophthalmology Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China.
Choy
Kwong Wai
KW
Cheung
Kin Fai
KF
Lam
D S C
DS
Fu
Wei Ling
WL
Pang
Chi Pui
CP
D002675:Child, Preschool; D002877:Chromosomes, Human / Q000235:genetics*; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D041321:Chromosomes, Human, X / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D007223:Infant; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D019572:Retinal Neoplasms / Q000235:genetics*; D012175:Retinoblastoma / Q000235:genetics*
D004273:DNA, Neoplasm