Clinical features and molecular analysis of a family with multiple colon tumours and reduced plasminogen activator activity.
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.
Tomlinson
I P
IP
Cancer Genetics Laboratory, Imperial Cancer Research Fund, London, UK.
Beck
N E
NE
Williamson
J
J
Harocopos
C J
CJ
Mitchell
V E
VE
Hodgson
S V
SV
Bodmer
W F
WF
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*
D010959:Tissue Plasminogen Activator