Rapid Next-Generation Sequencing Method for Prediction of Prostate Cancer Risks

摘要

Prostate cancer is the most commonly diagnosed male cancer and the second leading cause of cancer deaths among men in the United States, with approximately 220,000 new diagnoses and approximately 27,000 deaths each year. Men with clinical low-risk disease can receive active surveillance to safely preserve quality of life, provided that the risk of an undetected aggressive cancer can be managed. Thus, prediction of a tumor's metastatic potential, ideally using only a biopsy sample, is critical to choosing appropriate treatment. We previously proposed and verified a metastasis potential score (MPS) based on regions prone to copy number alterations in metastatic prostate cancer; MPS is highly predictive of metastatic potential in primary tumors. We developed a novel, targeted postligation amplification sequencing approach, which we call the next-generation copy number alteration assay, to efficiently interrogate 902 genomic sites that belong to 194 genomic regions used in the MPS calculation. The assay is designed to work with the latest generation of sequencing platforms to produce estimates of copy number alteration events. The assay's technical reproducibility, robustness to low starting genomic material, and accuracy have been verified. The assay performed very well on cell lines, a cohort of prostate cancer surgical research samples, and matched punched biopsy samples, making it a significant step toward incorporating sequencing techniques for prostate cancer evaluation.