Bladder tumour-derived somatic TSC1 missense mutations cause loss of function via distinct mechanisms.

ABSTRACT: More than 50% of transitional cell carcinomas of the bladder show loss of heterozygosity of a region spanning the TSC1 locus at 9q34 and mutations of TSC1 have been identified in 14.5% of tumours. These comprise nonsense mutations, splicing mutations, small deletions and missense mutations. Missense mutations are only rarely found in the germline in TSC disease. Therefore, we have examined six somatic missense mutations found in bladder cancer to determine whether these result in loss of function. We describe loss of function via distinct mechanisms. Five mutations caused mutually exclusive defects at mRNA and protein levels. Of these, two mutations caused pre-mRNA splicing errors that were predicted to result in premature protein truncation and three resulted in markedly reduced stability

SUBMITTER: Pymar LS 

PROVIDER: S-EPMC2427143 | biostudies-literature | 2008 Jul

REPOSITORIES: biostudies-literature