Prostate cancer aggressiveness locus on chromosome segment 19q12-q13.1 identified by linkage and allelic imbalance studies.
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.
Neville
Phillippa J
PJ
Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Conti
David V
DV
Krumroy
Lisa M
LM
Catalona
William J
WJ
Suarez
Brian K
BK
Witte
John S
JS
Casey
Graham
G
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
D005819:Genetic Markers