C79
Mutation analysis of the MSMB gene and its upstream region in familial prostate cancer
Zsofia Kote-Jarai1, Daniel Leongamornlert1, Malgorzata Tymrakiewicz1, Helen Field2, Michelle Guy1, Lynne O'Brien1, Rosemary Wilkinson1, Amanda Hall1, Kenneth Muir3, Aritaya Lophatananon3, Freddy Hamdy4, Jenny Donovan5, David Neal2, Douglas Easton2, Rosalind Eeles1
1The Institute of Cancer Research, Sutton, UK, 2University of Cambridge, UK, 3University of Nottingham, UK, 4University of Oxford, UK, 5University of Bristol, UK
Background
We recently identified MSMB, a gene coding for -microseminoprotein, as
a candidate susceptibility gene for prostate cancer. The protein product,
PSP94, has previously reported to have a reduced expression in prostate cancer
and has been suggested as an independent marker for recurrence of prostate
cancer after radical prostatectomy.
Method and Results
We have sequenced the whole gene transcript including ~1,500 bps upstream of the 5 UTR of MSMB in 192 prostate cancer cases with a strong family history. No deleterious mutation was identified, however 11 new sequence variants (SNPs) were found. In addition previously characterised SNPs were also evaluated in this familial DNA set. Four of the novel rare variants are in the 5 UTR region, in addition to 6 previously known SNPs. This region is the proximal promoter region for MSMB and various regulatory sequence elements have been found here. In silico analysis has shown that two of the SNPs here have an effect on transcription factor binding sites, one of which includes androgen, progesterone and aldosterone receptor binding sites.
Conclusion
Our results suggest that sequence variants identified in the promoter region
might modify gene expression by altering TF binding sites and this may be the
mechanism which is increasing prostate cancer risk.
