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Use of Magnetic Resonance Imaging and Biopsy Data to Guide Sampling Procedures for Prostate Cancer Biobanking
Published on: October 10, 2019
Bone biopsy protocol for advanced prostate cancer in the era of precision medicine
Verena Sailer1,2, Marc H Schiffman3, Myriam Kossai1,2
1Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York.
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/μL and 16.2 ng/μL, 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.
Insights
Obtaining prostate cancer bone biopsies for genomic studies is challenging but feasible. This protocol yields high-quality DNA and RNA for sequencing, identifying actionable targets and resistance mechanisms in advanced prostate cancer.
Area of Science:
- Oncology
- Genomics
- Surgical Pathology
Background:
- Metastatic biopsies are crucial for advanced prostate cancer to identify targets and resistance mechanisms.
- Sclerotic bone metastases present significant challenges for tissue acquisition.
- Adequate tissue is essential for both clinical diagnosis and genomic studies.
Purpose of the Study:
- To establish and evaluate a protocol for image-guided bone biopsies in prostate cancer patients.
- To assess the feasibility of obtaining high-quality DNA and RNA from bone metastases for next-generation sequencing.
- To identify actionable genomic alterations and resistance mechanisms in advanced prostate cancer.
Main Methods:
- Prospective enrollment of prostate cancer patients with bone metastases (February 2013-March 2017).
- Image-guided bone biopsy collection with fresh processing for diagnosis and freezing for sequencing.
- Whole-exome sequencing (WES) and RNA sequencing performed on extracted DNA and RNA.
Main Results:
- 70 bone biopsies from 64 patients were performed, with 85.7% diagnostic success for prostate cancer.
- Successful WES achieved in 81.7% and RNA sequencing in 33.3% of diagnostic cases.
- Median DNA and RNA yields were sufficient for molecular analysis; recurrent gene alterations were identified.
Conclusions:
- The developed prostate cancer bone biopsy protocol provides a valuable source of high-quality nucleic acids.
- This method enables tumor sequencing to detect actionable alterations and resistance mechanisms.
- The protocol supports personalized treatment strategies for patients with bone metastases.
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