Comprehensive resequence analysis of a 97 kb region of chromosome 10q11.2 containing the MSMB gene associated with prostate cancer.
Genome-wide association studies of prostate cancer have identified single nucleotide polymorphism (SNP) markers in a region of chromosome 10q11.2, harboring the microseminoprotein-β (MSMB) gene. Both the gene product of MSMB, the prostate secretory protein 94 (PSP94) and its binding protein (PSPBP), have been previously investigated as serum biomarkers for prostate cancer progression. Recent functional work has shown that different alleles of the significantly associated SNP in the promoter of MSMB found to be associated with prostate cancer risk, rs10993994, can influence its expression in tumors and in vitro studies. Since it is plausible that additional variants in this region contribute to the risk of prostate cancer, we have used next-generation sequencing technology to resequence a ~97-kb region that includes the area surrounding MSMB (chr10: 51,168,025-51,265,101) in 36 prostate cancer cases, 26 controls of European origin, and 8 unrelated CEPH individuals in order to identify additional variants to investigate in functional studies. We identified 241 novel polymorphisms within this region, including 142 in the 51-kb block of linkage disequilibrium (LD) that contains rs10993994 and the proximal promoter of MSMB. No sites were observed to be polymorphic within the exons of MSMB.
Yeager
Meredith
M
Core Genotyping Facility, SAIC-Frederick, Inc., NCI-Frederick, Frederick, MD 21702, USA. yeagerm@mail.nih.gov
Deng
Zuoming
Z
Boland
Joseph
J
Matthews
Casey
C
Bacior
Jennifer
J
Lonsberry
Victor
V
Hutchinson
Amy
A
Burdett
Laura A
LA
Qi
Liqun
L
Jacobs
Kevin B
KB
Gonzalez-Bosquet
Jesus
J
Berndt
Sonja I
SI
Hayes
Richard B
RB
Hoover
Robert N
RN
Thomas
Gilles
G
Hunter
David J
DJ
Dean
Michael
M
Chanock
Stephen J
SJ
D002879:Chromosomes, Human, Pair 10; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D011110:Polymorphism, Genetic; D011471:Prostatic Neoplasms / Q000235:genetics*; D029584:Prostatic Secretory Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA / Q000379:methods*
D029584:Prostatic Secretory Proteins; C043076:beta-microseminoprotein