title: Clinical features and molecular analysis of a family with multiple colon tumours and reduced plasminogen activator activity.
abstract: A family is reported in which a pair of brothers has developed recurrent venous thromboses, which have been shown in one brother (the proband) to result from a reduced level of tissue plasminogen activator (t-PA) activity. Both brothers have also developed multiple synchronous and metachronous colorectal adenomas. Other pedigree members have developed colon cancers, but not multiple colonic tumours. We have shown that HNPCC and FAP/AAPC are unlikely causes of the family's phenotypes. Previous studies have found low levels of t-PA in sporadic colon tumours. In this family, mutations in the t-PA gene, at a linked locus, or at a locus controlling t-PA activity/release may modify the colon tumour phenotype to cause multiple lesions.
authors.affiliation: Cancer Genetics Laboratory, Imperial Cancer Research Fund, London, UK.
authors.forename: I P
authors.initials: IP
authors.lastname: Tomlinson
authors.forename: N E
authors.initials: NE
authors.lastname: Beck
authors.forename: J
authors.initials: J
authors.lastname: Williamson
authors.forename: C J
authors.initials: CJ
authors.lastname: Harocopos
authors.forename: V E
authors.initials: VE
authors.lastname: Mitchell
authors.forename: S V
authors.initials: SV
authors.lastname: Hodgson
authors.forename: W F
authors.initials: WF
authors.lastname: Bodmer
mesh_terms: D000236:Adenoma / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D008875:Middle Aged; D009378:Neoplasms, Multiple Primary / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D010375:Pedigree; D013924:Thrombophlebitis / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D010959:Tissue Plasminogen Activator / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics*
chemical_list: D010959:Tissue Plasminogen Activator