Chromosome breakage in lymphocytes from members of cancer families showing autosomal dominant inheritance

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Abstract
We have conducted investigations on members of three families with increased predisposition to cancer which appears to be inherited as an autosomal dominant trait. The aim of our studies overall is to provide markers for the mutant genes involved, so that gene carriers may be monitored closely for signs of malignant disease. This paper reports on studies of chromosome breakage in lymphocytes from affected and at-risk family members and control subjects. No increase in spontaneous chromosome breakage was observed in family members compared with controls. An increased sensitivity to chromosome damage induced by the alkylating agent, N-methyl-N1-nitro-N-nitrosoguanidine (MNNG), was observed in three members from two families; one person was affected, the others at risk. These families included cases of osteosarcoma, in addition to various types of cancer of epithelial origin. Two members (one affected, one at-risk) of a third family showed increased sensitivity to the radio-mimetic agent, bleomycin. This family appeared to represent the cancer family syndrome. Whilst not conclusive at present, our results appear to justify investigation of members of cancer families with respect to sensitivity to chromosome breaking agents.