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Bone biopsy protocol for advanced prostate cancer in the era of precision medicine.

ABSTRACT: BACKGROUND:Metastatic biopsies are increasingly being performed in patients with advanced prostate cancer to search for actionable targets and/or to identify emerging resistance mechanisms. Due to a predominance of bone metastases and their sclerotic nature, obtaining sufficient tissue for clinical and genomic studies is challenging. METHODS:Patients with prostate cancer bone metastases were enrolled between February 2013 and March 2017 on an institutional review board-approved protocol for prospective image-guided bone biopsy. Bone biopsies and blood clots were collected fresh. Compact bone was subjected to formalin with a decalcifying agent for diagnosis; bone marrow and blood clots were frozen in optimum cutting temperature formulation for next-generation sequencing. Frozen slides were cut from optimum cutting temperature cryomolds and evaluated for tumor histology and purity. Tissue was macrodissected for DNA and RNA extraction, and whole-exome sequencing and RNA sequencing were performed. RESULTS:Seventy bone biopsies from 64 patients were performed. Diagnostic material confirming prostate cancer was successful in 60 of 70 cases (85.7%). The median DNA/RNA yield was 25.5?ng/?L and 16.2?ng/?L, respectively. Whole-exome sequencing was performed successfully in 49 of 60 cases (81.7%), with additional RNA sequencing performed in 20 of 60 cases (33.3%). Recurrent alterations were as expected, including those involving the AR, PTEN, TP53, BRCA2, and SPOP genes. CONCLUSIONS:This prostate cancer bone biopsy protocol ensures a valuable source for high-quality DNA and RNA for tumor sequencing and may be used to detect actionable alterations and resistance mechanisms in patients with bone metastases. Cancer 2018;124:1008-15. © 2017 American Cancer Society.

SUBMITTER: Sailer V

PROVIDER: S-EPMC5821525 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Bone biopsy protocol for advanced prostate cancer in the era of precision medicine.

Sailer Verena V Schiffman Marc H MH Kossai Myriam M Cyrta Joanna J Beg Shaham S Sullivan Brian B Pua Bradley B BB Lee Kyungmouk Steve KS Talenfeld Adam D AD Nanus David M DM Tagawa Scott T ST Robinson Brian D BD Rao Rema A RA Pauli Chantal C Bareja Rohan R Beltran Luis S LS Sigaras Alexandros A Eng Kenneth Wa KW Elemento Olivier O Sboner Andrea A Rubin Mark A MA Beltran Himisha H Mosquera Juan Miguel JM

Cancer 20171219 5

<h4>Background</h4>Metastatic biopsies are increasingly being performed in patients with advanced prostate cancer to search for actionable targets and/or to identify emerging resistance mechanisms. Due to a predominance of bone metastases and their sclerotic nature, obtaining sufficient tissue for clinical and genomic studies is challenging.<h4>Methods</h4>Patients with prostate cancer bone metastases were enrolled between February 2013 and March 2017 on an institutional review board-approved pr ...[more]

PMID: 29266381

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Project description:Prostate cancer is the most common malignancy in men in the United States. While androgen deprivation therapy results in tumor responses initially, there is relapse and progression to metastatic castration-resistant prostate cancer. Currently, all prostate cancer patients receive essentially the same treatment, and there is a need for clinically applicable technologies to provide predictive biomarkers toward personalized therapies. Genomic analyses of tumors are used for clinical applications, but with a paucity of obvious driver mutations in metastatic castration-resistant prostate cancer, other applications, such as phosphoproteomics, may complement this approach. Immunohistochemistry and reverse phase protein arrays are limited by the availability of reliable antibodies and evaluates a preselected number of targets. Mass spectrometry-based phosphoproteomics has been used to profile tumors consisting of thousands of phosphopeptides from individual patients after surgical resection or at autopsy. However, this approach is time consuming, and while a large number of candidate phosphopeptides are obtained for evaluation, limitations are reduced reproducibility, sensitivity, and precision. Targeted mass spectrometry can help eliminate these limitations and is more cost effective and less time consuming making it a practical platform for future clinical testing. In this review, we discuss the use of phosphoproteomics in prostate cancer and other clinical cancer tissues for target identification, hypothesis testing, and possible patient stratification. We highlight the majority of studies that have used phosphoproteomics in prostate cancer tissues and cell lines and propose ways forward to apply this approach in basic and clinical research. Overall, the implementation of phosphoproteomics via targeted mass spectrometry has tremendous potential to aid in the development of more rational, personalized therapies that will result in increased survival and quality of life enhancement in patients suffering from metastatic castration-resistant prostate cancer.

Dataset Information

Bone biopsy protocol for advanced prostate cancer in the era of precision medicine.

Publications

Bone biopsy protocol for advanced prostate cancer in the era of precision medicine.

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