Homozygosity of Chromosome 13 in Retinoblastoma

Abstract

We studied the frequency of chromosome 13 homozygosity in tumor tissue obtained directly from eyes harboring retinoblastomas. The data indicate that approximately half of all retinoblastomas are homozygous for large portions of 13q, that the homozygosity occurs in vivo and not as an event secondary to culture of the tumor cells, that chromosome 13 homozygosity is not correlated with the degree of histopathologic differentiation of the tumor, and that the homozygosity occurs in both sporadic and hereditary retinoblastomas. The development of chromosome 13 homozygosity may represent a fundamental event in the oncogenesis of a considerable number of retinoblastomas. This finding may have implications for the genetic counseling of patients with hereditary retinoblastoma. It may also be important in understanding the mechanism of oncogenesis of other tumors, especially hereditary tumors.

Structural alterations of the RB1 gene in human soft tissue tumours

“…The nature of the deletions which give rise to these abnormal band patterns is illustrated in Figure 2, (Enzinger & Weiss, 1988). The prevalence of individual histological types in our series of 69 primary tumours (Table I) is similar to that reported in the general population (Enzinger & Weiss, 1988) (Cavenee et al, 1983;Dryja et al, 1984;Hansen et al, 1985;Benedict et al, 1987;Toguchida et al, 1988 (Friend et al, 1987) three soft tissue tumours with homozygous RB1 deletions were found. One of these was also in a leiomyosarcoma, one in an MFH and the last case was unclassified.…”

Definition of the minimal simian virus 40 large T antigen- and adenovirus E1A-binding domain in the retinoblastoma gene product.

“…Previous studies indicated that the risk of developing retinoblastoma was linked to abnormalities, including deletions, of the long arm of chromosome 13 (2,7,16,48). Further studies suggested that inactivation of both alleles of a sequence mapping to chromosome 13q14 was a necessary event in the pathogenesis of this tumor, consistent with the notion that this region harbored a tumor suppressor gene (4,40).…”

The ecology of brain tumors: lessons learned from neurofibromatosis-1

“…For example, in familial retinoblastoma (RB), patients are heterozygous for an inactivating mutation in the retinoblastoma tumor suppressor gene. RB tumors develop following bi-allelic inactivation of the RB gene (Cavenee et al, 1983;Dryja et al, 1984). As children born with a germline RB mutation require only one additional genetic alteration, the loss of the one remaining functional allele, the incidence of RB tumor formation is much higher and occurs at an earlier age than observed in the general population, where both RB alleles must be inactivated in the same cell for tumors to develop (Knudson, 1971).…”