Prostate cancer aggressiveness locus on chromosome 7q32-q33 identified by linkage and allelic imbalance studies.
The biologic aggressiveness of prostate tumors is an important indicator of prognosis. Chromosome 7q32-q33 was recently reported to show linkage to more aggressive prostate cancer, based on Gleason score, in a large sibling pair study. We report confirmation and narrowing of the linked region using finer-scale genotyping. We also report a high frequency of allelic imbalance (AI) defined within this locus in a series of 48 primary prostate tumors from men unselected for family history or disease status. The highest frequency of AI was observed with adjacent markers D7S2531 (52%) and D7S1804 (36%). These two markers delineated a common region of AI, with 24 tumors exhibiting interstitial AI involving one or both markers. The 1.1-Mb candidate region contains relatively few transcripts. Additionally, we observed positive associations between interstitial AI at D7S1804 and early age at diagnosis (P=.03) as well as a high combined Gleason score and tumor stage (P=.06). Interstitial AI at D7S2531 was associated with a positive family history of prostate cancer (P=.05). These data imply that we have localized a prostate cancer tumor aggressiveness loci to chromosome 7q32-q33 that is involved in familial and nonfamilial forms of prostate cancer.
Department of Cancer Biology, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Phillippa J
PJ
Neville
David V
DV
Conti
Pamela L
PL
Paris
Howard
H
Levin
William J
WJ
Catalona
Brian K
BK
Suarez
John S
JS
Witte
Graham
G
Casey
D000368:Aged; D022981:Allelic Imbalance / Q000235:genetics*; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D008040:Genetic Linkage / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009367:Neoplasm Staging; D011471:Prostatic Neoplasms / Q000235:genetics*; D021101:Radiation Hybrid Mapping
D004273:DNA, Neoplasm