In several ocular and nonocular cancer types, including familial and sporadic retinoblastoma, osteosarcoma, small cell lung cancer (SCLC), breast cancer, prostate cancer, and others, frequent loss or inactivation of the retinoblastoma tumor suppressor gene (Rb7) on chromosome 13q14.2 is associated with turnorigenesis 11-1 01. This does not appear to be so in the case of colorectal cancer. Colorectal carcinomas show infrequent (0-1 1 %) allelic loss at various restriction fragment length polymorphism (RFLP) loci on chromosome 13 (Table l), including those within the Rb I gene [ 1 1,121; moreover, cytogenetic studies show nonrandom gains of chromosome 13, including trisomy and tetrasomy, in approximately 50% of such tumors [ 13,141. Paralleling these karyological findings, we have shown twofold to threefold increases in allele copy number at the Rb 7 locus in over 40% of colorectal carcinomas (Table 1) [11,15]. This finding of increased Rbl allele copy number was recently confirmed by Meling et al. [I 2 1 (Table I), who observed it for one Rb 7 allele in 30% of tumors from 156 informative individuals. Even more recently, Lothe et al.
[16] studied two RFLP loci within the Rb7 gene plus five flanking loci in 32 colorectal carcinomas and found not only increases in allelic copy number at these loci in 1 1 tumors (32%) but also increases in copy number within the Rb7 gene in three of these 1 1 tumors without seeing corresponding changes in the flanking loci. This may indicate that gain of particular chromosome 13 sequences, including the 17/11 locus, is involved in colorectal tumorigenesis.
OVEREXPRESSION OF Rb7 MESSAGE IN COLORECTAL CARCINOMAS
Because of the evidence for increases in Rb 1 copy number in colorectal carcinomas, we and others analyzed the expression and gross structure of the Rb 7 gene. To date, no gross genetic structural alterations have been observed in these tumors by Southern blot analysis; moreover, we demonstrated that 38 primary colorectal cancers and four colorectal carcinoma cell lines had Rb 1 normal-sized transcripts (4.7 kb) [15].