Distinct genomic alterations in prostate cancers in Chinese and Western populations suggest alternative pathways of prostate carcinogenesis.
Prostate cancer is significantly more common in Western men than in Asian men, but the basis for this difference remains unknown. Because genomic studies of Asian prostate cancer are very limited, we used a genome-wide approach to reveal the genomic alterations in Chinese prostate cancers. We found a significant reduction in the frequency of certain somatic genomic changes that are commonly found in Western prostate cancers, including the 21q22.2-22.3 deletion, which involves the TMPRSS2:ERG fusion gene, and 10q deletion, which causes PTEN inactivation. Array results were confirmed by PCR-based molecular copy-number counting in selected samples. The different frequencies of these genomic changes were further evaluated by fluorescent in situ hybridization and immunohistochemistry analyses of tissue microarray samples. These alterations might be key genetic changes underlying the regional/ethnic difference in clinical incidence and might be induced by specific environmental and/or genetic risk factors that Western men are exposed to. Our findings suggest that tumors arise in Western and Chinese populations by alternative pathogenetic mechanisms.
Molecular Oncology & Imaging Centre, Medical Oncology Centre, Institute of Cancer, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
Xueying
X
Mao
Yongwei
Y
Yu
Lara K
LK
Boyd
Guoping
G
Ren
Dongmei
D
Lin
Tracy
T
Chaplin
Sakunthala C
SC
Kudahetti
Elzbieta
E
Stankiewicz
Liyan
L
Xue
Luis
L
Beltran
Manu
M
Gupta
R Tim D
RT
Oliver
Nick R
NR
Lemoine
Daniel M
DM
Berney
Bryan D
BD
Young
Yong-Jie
YJ
Lu
D044466:Asian People / Q000235:genetics*; D002681:China; D015321:Gene Rearrangement; D015894:Genome, Human; D006801:Humans; D008297:Male; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D051059:PTEN Phosphohydrolase / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000208:ethnology* / Q000235:genetics* / Q000473:pathology; D015534:Trans-Activators / Q000235:genetics; D000071230:Transcriptional Regulator ERG; D006113:United Kingdom; D044465:White People / Q000235:genetics*
C072312:ERG protein, human; D015514:Oncogene Proteins, Fusion; C515553:TMPRSS2-ERG fusion protein, human; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human