Conference on health consequences of environmental controls: impact of mobile emissions controls. The public interest: overview.

In 231 colorectal carcinomas, allele variation at four restriction fragments length polymorphisms (RFLP) loci on chromosome 17 have been studied by Southern analysis. Heterozygous loss of the TP53 gene was found in 68% (129/189) of the carcinomas informative on both chromosome arms. In 41% (77/189) of the carcinomas the loss was found only on 17p. Two probes were used to detect alterations on 17p, pBHP53 and pYNZ22. When loss was demonstrated with pYNZ22, pBHP53 also always showed loss (n = 45), whereas when loss was demonstrated with pBHP53, only 45 of 54 (83%) showed loss with pYNZ22. Loss on 17q was found in 34% (64/189) of the carcinomas, and 6% (12/189) had loss on this chromosome arm, only. Loss on 17q was significantly associated with loss on 17p (P <0.01). These data confirm that the TP53 gene is the target of loss on chromosome arm 17p in colorectal carcinomas, and demonstrate that loss of the TP53 gene is most frequently part of limited, subchromosomal loss. Furthermore, the results do not suggest any additional tumour suppressor gene(s) on chromosome 17 involved in colorectal carcinogenesis. The role of loss of DNA sequences in carcinogenesis is a matter of considerable interest, especially since such allele loss may indicate the presence of a target suppressor gene within the lost region (Knudson, 1985). A high frequency of loss on chromosome arm 17p has been reported in colorectal carcinomas (Fearon et al. and one target of this loss has been shown to be the TP53 gene (for review, Levine et al., 1991). Furthermore, most of the colorectal carcinomas with loss of one TP53 gene allele have revealed TP53 point mutations on the remaining allele, resulting in a functionally inactive TP53 gene. However, the chromosomal extent of the loss comprising the TP53 gene locus, and thereby the relevance of loss detected on chromosome arm 17p as a reflection of changes of the TP53 gene, is not similarly well characterised. Allele amplification in colorectal carcinomas has so far not been extensively studied by Southern analysis. The reason might be that this genetic alteration is less frequently observed than loss of heterozygosity, and because the concept of tumour suppressor genes implies loss rather than gain of DNA sequences. We have recently demonstrated allele amplification within the Rb gene in 30% of colorectal car-cinomas (Meling et al., 1991), suggesting a role also for amplified genes in carcinogenesis in the colorectum. …