We have analyzed the 27 exons and the promoter region of the RB1 gene in familial or sporadic bilateral retinoblastoma by using single-strand conformation polymorphism analysis.
The genetic hallmark of retinoblastoma is mutation or deletion of the RB1 gene, whereas other genetic alterations that are also required are largely unknown.
Sixty-nine primary soft tissue tumours were examined for alterations of the RB1 gene which has previously been implicated in the genesis of retinoblastoma.
[S. H. Friend, R. Bernards, S. Rogelj, R. A. Weinberg, J. M. Rapaport, D. M. Albert, and T. P. Dryja, Nature (London) 32:643-646, 1986] reported the cloning of a gene, 4.7R, with some properties expected for the RB1 gene, namely, a high frequency (30%) of genomic rearrangements in tumors and absence of message in all RB tumors examined.
Examples include the RB1 gene for retinoblastoma; the WT1 gene for Wilms' tumor; germline p53 mutations in families with the Li-Fraumeni syndrome; the NF1 and NF2 genes for neuroblastomatosis, types 1 and 2; the VHL gene for renal cancer and other tumors associated with Von Hippel-Lindau disease; the APC gene for adenomatous polyposis coli; the BRCA1 gene for hereditary breast and ovarian cancer; and the mismatch repair genes for colon and other common cancers.
Mutations of the Rb1 gene are now commonly believed to be the "cause" retinoblastoma, although epidemiological, clinical, and biological evidences argue against it.
Almost all patients with sporadic bilateral and virtually all patients with familial Rb are heterozygous for RB1 gene mutations that cause predisposition to Rb (hereditary Rb).