CLINICAL-FEATURES AND MOLECULAR ANALYSIS OF A FAMILY WITH MULTIPLE COLON TUMORS AND REDUCED PLASMINOGEN-ACTIVATOR ACTIVITY

A family is reported in which a pair of brothers has developed recurre nt venous thromboses, which have been shown in one brother (the proban d) to result from a reduced level of tissue plasminogen activator (t-P A) activity. Both brothers have also developed multiple synchronous an d metachronous colorectal adenomas. Other pedigree members have develo ped colon cancers, but not multiple colonic rumours. We have shown tha t HNPCC and FAP/AAPC are unlikely causes of the family's phenotypes. P revious studies have found low levels of t-PA in sporadic colon tumour s. In this family, mutations in the t-PA gene, at a linked locus, or a t a locus controlling t-PA activity/release may modify the colon tumou r phenotype to cause multiple lesions.