School of Informatics, Computing and Cyber Systems, Northern Arizona State University, Flagstaff, Arizona.
Department of Pathology, Albert Einstein College of Medicine, Bronx, New York.
J Mol Diagn. 2019 Jan;21(1):49-57. doi: 10.1016/j.jmoldx.2018.07.007. Epub 2018 Dec 12.
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.
前列腺癌是美国男性最常见的癌症，也是男性癌症死亡的第二大主要原因，每年约有 22 万新病例和约 2.7 万人死亡。患有临床低危疾病的男性可以通过主动监测安全地维持生活质量，前提是可以控制未检测到的侵袭性癌症的风险。因此，预测肿瘤的转移潜力，理想情况下仅使用活检样本，对于选择适当的治疗方法至关重要。我们之前提出并验证了一种基于转移性前列腺癌中易发生拷贝数改变的区域的转移潜力评分（MPS）；MPS 高度预测原发性肿瘤的转移潜力。我们开发了一种新的靶向连接后扩增测序方法，我们称之为下一代拷贝数改变检测，以有效地检测属于 MPS 计算中使用的 194 个基因组区域的 902 个基因组位点。该检测旨在与最新一代测序平台配合使用，以生成拷贝数改变事件的估计值。该检测的技术重复性、对低起始基因组材料的稳健性和准确性已得到验证。该检测在细胞系、前列腺癌手术研究样本队列和匹配的活检样本中表现非常出色，这是将测序技术纳入前列腺癌评估的重要一步。
