Allelic imbalance at 13q14.2 approximately q14.3 in localized prostate cancer is associated with early biochemical relapse.
Allelic imbalance (AI), particularly at chromosomes 8p, 10q, and 13q, is the most frequently observed genetic change in sporadic prostate cancer. AI at these sites may inactivate tumor suppressor genes that regulate normal cell growth. To establish the relationship between AI and progression, we analyzed loci on 8p, 10q, and 13q14 in archival prostate tumors matched for Gleason grade, pre-operative prostate-specific antigen levels, and pathologic stage, and they were paired on the basis of relapse status after 3 years. AI was identified in 66% of patients without relapse and in 73% with relapse. There was no statistically significant difference for AI at 8p21.3 and 10q23.2 between the two groups of patients, but significant differences between relapsers and nonrelapsers in the frequency of AI at D13S165 at 13q14.2 (P=0.006) and D13S273 at 13q14.3 (P=0.03). There was also a significantly higher incidence of AI at both loci in the relapsers compared to the nonrelapsers (P=0.03). In three relapsers, AI occurred at all three loci between 13q14.2 and 13q14.3, with no nonrelapsers demonstrating AI at all three loci. These findings show that AI at 13q14.2 approximately q14.3 is an important event in the progression of localized prostate cancer, and suggest a possible role for microRNAs.
Prostate Cancer Research Centre, Institute of Urology, University College London, 67 Riding House Street, London W1W 7EJ, United Kingdom.
Nicola
N
Brookman-Amissah
Joseph
J
Nariculam
Alex
A
Freeman
Magali
M
Willamson
Roger S
RS
Kirby
John R
JR
Masters
Mark R
MR
Feneley
D000368:Aged; D022981:Allelic Imbalance; D002879:Chromosomes, Human, Pair 10; D002882:Chromosomes, Human, Pair 13; D002898:Chromosomes, Human, Pair 8; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics*