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Report on meeting on molecular studies of inherited cancer syndromes

As part of their regular programme of meetings the UK Cancer Families Study Group held a two day meeting on molecular aspects of familial cancer in the Paterson Laboratories, Christie Hospital, Manchester on 10 and 11 February 1986. The opening consideration of the occurrence of cancer in families emphasised the critical importance of accurate diagnosis and complete ascertainment as a basis for molecular studies. In particular, mildly affected subjects must be recognised and included in the affected group. The need for sub-classification was also stressed since, in some instances at least, strong familial association involved a specific type of pathology or a specific clinical presentation. Dr Ray Cartwright (Leeds) pointed out the need to consider genetic environmental interactions, since it appeared that a susceptible genotype might lead to the occurrence of the disease in only a minority of cases. The following section dealt with the methodologies. Dr Julia Bodmer (London) outlined classical linkage studies using the multiple alleles at the HLA loci. She also pointed out the power of sib pair analysis in such systems. Professor Bob Williamson (London) gave an optimistic forecast of the coverage of the human genome using restriction fragment length polymorphisms, though problems may arise from the fact that there may be only two alleles in many instances. Dr Steve Harris (Leicester) described the application of the minisatellite probes in general and in particular to some families with neurofibromatosis. In effect this was equivalent to scoring 25 to 35 loci in a single experiment. Sir Walter Bodmer (London) suggested, in discussion, that the same effect might be achieved by simply mixing known probes. Several speakers who have been using such technologies to investigate genetically determined disease not associated with cancer then outlined their experience. It became clear that while enormous advances had been made in locating known genes or DNA probes close to the locus of interest, there still remained formidable problems in actually isolating the gene in question. Dr Susan Kenwrick (Oxford) presented elegant work on Duchenne muscular dystrophy, but even here with an X linked gene and many closely linked probes, the results are still puzzling and could suggest rearrangements near the DMD locus at least in some cases. The introduction of new techniques, such as pulsed field electrophoresis and new multiple point methods of analysis, are, however, holding out hope for rapid progress. On the second day, discussion moved on to specific chromosome regions or specific loci associated with cancer. Dr Nick Hastie (Edinburgh) described recent progress on the analysis of the region near lipl3 which is associated with the Wilms'-aniridiagenitourinary syndrome and other childhood cancers such as rhabdomyosarcoma. In particular, chromosome mediated gene transfer is proving to be a powerful technique for the analysis of chromosome regions rather than specific loci. Dr Peter Little (London), again focusing on chromosome 11, gave a lucid and detailed account of the possibilities of molecular analyses of such regions of interest. He emphasised that while much of the technology is already available it will certainly take some time and a bit of luck to come up with meaningful answers. Techniques such as the overlapping cosmid technique for'walking' are, however, adding to the power of these methodologies. Similar problems face those attempting to analyse the retinoblastoma region at chromosome 13ql4. Dr John Cowell (London) outlined progress in this field and mentioned one instance of the kind of luck that is required for quick progress, namely a translocation t(1;13) which may have its breakpoint in the retinoblastoma locus. Malcolm Taylor (Birmingham) outlined some exciting new results which place the breakpoints for the specific rearrangements seen in ataxia telangiectasia lymphocytes outside, and proximal to, the immunoglobulin heavy chain locus (and therefore different from the 14q32 breakpoint in Burkitt's lymphoma) and close to the a chain locus of the T cell receptor at 14q11. Consideration of other diseases where attempts at genetic analysis are being made emphasised the need for close liason between clinicans, cell biologists, and molecular geneticists. The chromosomal locations of neurofibromatosis, polyposis coli, and MEN 2 are still not clear. Dr Bruce Ponder (London) pointed out