Monoclonal origin of multifocal cancer and the step-wise genetic events of prostate carcinogenesis


Session type:

Xueying Mao1, Lara Boyd1, Liyan Xue1, Dongmei Lin1, Tracy Chaplin1, Lius Beltran2, Greg Shaw1, John Hines2, Tim Oliver1, Daniel Berney1, Bryan Young1, Yong-Jie Lu1
1Queen Mary University of London, London, UK, 2Whipps Cross Hospital, London, UK


Prostate cancer is commonly detected as multiple foci in a single prostate gland and it is of etiological and clinical importance to identify the origin of these multifocal cancer lesions. Due to the limited number of markers analysed, previous studies to address this issue are inconclusive.


We used a high-resolution, genome-wide, SNP array to analyse genomic alterations in 43 cancer and high-grade prostatic intraepithelial neoplasia (HGPIN) foci from 16 prostate cancer cases to determine the genomic similarities/differences of these foci within the same prostate gland.


Identical copy number gains and losses shared by all cancer foci were detected in 11/11 informative case-matched multifocal tumour cases, suggesting that multiple cancer foci arise from a common prostate cancer precursor clone. A higher degree of similarity was also observed between HGPIN and adjacent cancer foci. Identical genomic copy-number changes were detected in all foci of HGPINs in two cases where more than one HGPIN foci were available, indicating at least in certain cases, a malignant precursor can cause separate PIN foci. Microarray data were confirmed by fluorescence in situ hybridisation in selected foci. Based on the monoclonal model, we determined the step-wise accumulation of genomic changes. Loss of 10q23.2-10q23.31 and 16q were commonly shared in same-case tumour foci and, in many cases, also matched PIN foci, suggesting that they may be early events in prostate carcinogenesis. Other common genomic changes, such as loss of 6q, 8p and 21q22.2-21q22.3, were found less frequently in all same-case foci and in PIN lesions, suggesting these genetic events may occur at a relatively later stage.


In conclusion, we revealed a monoclonal origin for the majority of multiple foci prostate cancer samples analysed. We have also begun to elucidate the step-wise genetic events in prostate carcinogenesis, including loss of 10q23.2-10q23.31 as an cancer initiation event.