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Loss of heterozygosity (LOH) at adenomatous polyposis coli (APC) and mutated in colon cancer (MCC) genes was investigated in 37 untreated human primary oral squamous cell carcinomas (SCCs) using the polymerase chain reaction. LOH was observed in 14 of 26 (53.8%) heterozygous (informative) patients at APC and 9 of 13 (69.2%) heterozygous patients at MCC> Homozygous deletion of MCC was detected in one patient. Of the 37 patients, 29 were informative at APC or MCC or both; LOH at APC and/or MCC was detected in 68.9% (20/29) of the cases. Ten cases were informative for both genes; LOH at both loci was found in only three of these cases. LOH at the APC and/or MCC was found in both early and advanced stages of oral SCCs. No significant correlation was observed between LOH at the APC and/or MCC locus and the patients' tobacco/betel quid consumption, tumour location, TNM status, or histological differentiation. These results suggest that LOH at the APC and/or MCC may be an early event and may play a role in the pathogenesis of human oral SCCs in Taiwan.

Tumor suppressor genes APC and MCC were identified recently, and their chromosomal location was ascribed to chromosome 5q21. Mutations in the APC gene give rise to familial adenomatous polyposis and occur in many perhaps even the majority, of sporadic colon cancers. Loss of heterozygosity has been described in other human tumors such as lung and esophageal cancers. Here we show loss of heterozygosity (LOH) in 87 patients with breast cancer for the APC and/or MCC loci using a polymerase chain reaction-LOH assay. LOH affected loci in APC exons 11 and 15 in 9 of 35 (25%) and 4 of 34 (11%) heterozygous patients, respectively. LOH at the MCC exon 10 locus occurred in 7 of 40 (17%) informative samples. These data suggest that allelic deletion of APC and/or MCC is probably involved in the pathogenesis and/or progression of a subset of breast cancers.

Very frequent loss of heterozygosity (LOH) on chromosome 3p has been found in human renal cell carcinoma (RCC). In the present study, we examined LOH at the retinoblastoma (RB), mutated in colorectal cancer (MCC) and adenomatous polyposis coli (APC) tumour suppressor genes loci, and mutations of the H-, K-, and N-ras oncogenes. We performed these studies using the polymerase chain reaction (PCR) method followed by restriction fragment length polymorphism (RFLP) and single-strand conformation polymorphism (SSCP) analyses. LOH was detected in 2 of 11 (18.2%), and 2 of 14 (14.3%) informative cases at the MCC and APC loci, respectively, and in none of 15 informative cases at the RB locus in 25 RCCs. LOH at the MCC was accompanied by LOH at the APC locus in two RCCs. No mutation was detected in H-, K-, and N-ras genes in 39 RCCs. Thus, alterations of the known tumour suppressor genes and the ras oncogenes were infrequent events in RCC. The results suggest that the genetic pathway in the genesis of RCC differs considerably from that of other common human carcinomas.