We present an extended family with LiFraumeni syndrome characterised by gastric and breast carcinoma, glioma, sarcoma, and leukaemia. This family showed strong evidence of linkage to TP53, and three of four tumours analysed showed loss of the wild type allele. A codon 175 missense mutation was identified in exon S in all available affected subjects. Counselling, screening, and issues surrounding presymptomatic testing are discussed. (J Med Genet 1995;32:942-945)
At present, there is conflicting evidence whether microsatellite instability (MSI) plays a role in the pathogenesis of breast cancer. Here we describe for the first time an MSI(+) phenotype in two breast cancer cell lines, CAL51 and MT-3, resembling that observed in colorectal cancers. These cell lines are characterized by near-diploid and hyperdiploid karyotypes, respectively. We detected MSI in these cell lines within two non-coding (BAT-25 and BAT-26) and within coding repeat sequences of genes known to be mutated in MSI(+) cancer (TGFBR2, IGF2R, BAX). We provide evidence that the inactivation of MMR genes is responsible for MSI in these cell lines.
O 6 -alkylguanine-DNA alkyltransferase (MGMT) repairs DNA adducts that result from alkylation at the O 6 position of guanine. These lesions are mutagenic and toxic and can be produced by a variety of agents ranging from carcinogens present in cigarette smoke to drugs used in cancer chemotherapy. There is a considerable amount of interindividual variation of MGMT activity and recent work has uncovered a series of polymorphisms that affect protein activity or are associated with differences in expression levels. On the other hand, current evidence for an association with cancer risk is tenuous: while some studies find such associations, others fail to support them. However, all published studies are based on small sample numbers. Not yet addressed are issues such as the relationship between sequence variation and the extent of the side effects of chemotherapy involving O 6 -alkylating agents. This review summarises the current state of knowledge in these areas.
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