title: Prostate cancer aggressiveness locus on chromosome segment 19q12-q13.1 identified by linkage and allelic imbalance studies.
abstract: Whole-genome scan studies recently identified a locus on chromosome segments 19q12-q13.11 linked to prostate tumor aggressiveness by use of the Gleason score as a quantitative trait. We have now completed finer-scale linkage mapping across this region that confirmed and narrowed the candidate region to 2 cM, with a peak between markers D19S875 and D19S433. We also performed allelic imbalance (AI) studies across this region in primary prostate tumors from 52 patients unselected for family history or disease status. A high level of AI was observed, with the highest rates at markers D19S875 (56%) and D19S433 (60%). Furthermore, these two markers defined a smallest common region of AI of 0.8 Mb, with 15 (29%) prostate tumors displaying interstitial AI involving one or both markers. In addition, we noted a positive association between AI at marker D19S875 and extension of tumor beyond the margin (P = 0.02) as well as a higher Gleason score (P = 0.06). These data provide strong evidence that we have mapped a prostate tumor aggressiveness locus to chromosome segments 19q12-q13.11 that may play a role in both familial and non-familial forms of prostate cancer.
authors.affiliation: Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
authors.forename: Phillippa J
authors.initials: PJ
authors.lastname: Neville
authors.forename: David V
authors.initials: DV
authors.lastname: Conti
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Krumroy
authors.forename: William J
authors.initials: WJ
authors.lastname: Catalona
authors.forename: Brian K
authors.initials: BK
authors.lastname: Suarez
authors.forename: John S
authors.initials: JS
authors.lastname: Witte
authors.forename: Graham
authors.initials: G
authors.lastname: Casey
mesh_terms: D000368:Aged; D022981:Allelic Imbalance / Q000235:genetics*; D002874:Chromosome Mapping / Q000379:methods; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics*; D008040:Genetic Linkage / Q000235:genetics*; D005819:Genetic Markers / Q000235:genetics*; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D016612:Paraffin Embedding; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery
chemical_list: D005819:Genetic Markers