Infrequent genomic rearrangement and normal expression of the putative RB1 gene in retinoblastoma tumors.

Retinoblastoma (RB) tumors develop when both alleles of a gene (RB1) are mutated and unable to function normally. Recently, Friend et al. [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. To extend the characterization of this gene, we used 4.7R probes to search for genomic rearrangements of DNA and to study the expression of the 4.7R gene in RB tumors, osteosarcoma (OS) tumors arising in RB patients, and other normal and malignant tissues. In 34 previously unreported RB and OS tumors arising in RB patients, we observed only four (12%) with genomic abnormalities. Transcripts of 4.7R were present in 12 of 17 RB tumors, 2 of 2 OS tumors, and all non-RB tumors and normal tissues tested. We were unable to confirm the high frequency of truncated messages of 4.7R in RB tumors reported by Lee et al. (W. H. Lee, R. Bookstein, F. Hong, L. J. Young, J. Y. Shaw, and E. Y. Lee, Science 235:1394-1399, 1987) and Fung et al. (Y. K. Fung, A. L. Murphree, A. Tang, J. Qian, S. H. Hinrichs, and W. F. Benedict, Science 236:1657-1661, 1987) but did confirm the presence of a truncated transcript in the RB cell line Y79. Of the RB and RB-related OS tumors which appeared normal on Southern blots, 2 of 26 or 12% had abnormal transcripts, giving a combined frequency of 22% abnormalities in the 4.7R gene detectable by Southern and Northern (RNA) blot analyses.