Abstract
The main guidelines and recommendations for the implementation of the BRCA1/2 somatic test do not focus on the clinical application of predictive testing on bone metastases, a frequent condition in metastatic prostate cancer, by analyzing the critical issues encountered by laboratory practice. Our goal is to produce a document (protocol) deriving from a multidisciplinary team approach to obtain high quality nucleic acids from biopsy of bone metastases. This document aims to compose an operational check-list of three phases: the pre-analytical phase concerns tumor cellularity, tissue processing, sample preservation (blood/FFPE), fixation and staining, but above all the decalcification process, the most critical phase because of its key role in allowing the extraction of somatic DNA with a good yield and high quality. The analytical phase involves the preparation of the libraries that can be analyzed in various NGS genetic sequencing platforms and with various bioinformatics software for the interpretation of sequence variants. Finally, the post-analytical phase that allows to report the variants of the BRCA1/2 genes in a clear and usable way to the clinician who will use these data to manage cancer therapy with PARP Inhibitors.
Similar content being viewed by others
References
Giunta EF, Annaratone L, Bollito E et al (2021) Molecular Characterization of Prostate Cancers in the Precision Medicine Era. Cancers 13(19):4771. https://doi.org/10.3390/cancers13194771
Halabi S, Kelly WK, Ma H et al (2016) Meta-analysis evaluating the impact of site of metastasis on overall survival in men with castration-resistant prostate cancer. J Clin Oncol 34:1652–1659
Bubendorf L, Schopfer A, Wagner U et al (2000) Metastatic patterns of prostate cancer: an autopsy study of 1,589 patients. Hum Pathol 31:578–583
Conteduca V, Mosca A, Brighi N, de Giorgi U, Rescigno P (2021) New Prognostic Biomarkers in Metastatic Castration-Resistant Prostate Cancer. Cells 10(1):193. https://doi.org/10.3390/cells10010193
Mateo J, Carreira S, Sandhu S et al (2015) DNA-repair defects and olaparib in metastatic prostate cancer. N Engl J Med 373:1697–1708
Robinson D, Van Allen EM, Wu YM et al (2015) Integrative clinical genomics of advanced prostate cancer. Cell 161:1215–1228
Van Allen EM, Foye A, Wagle N et al (2014) Successful whole-exome sequencing from a prostate cancer bone metastasis biopsy. Prostate Cancer Prostatic Dis 17:23–27
Zheng G, Lin MT, Lokhandwala PM et al (2016) Clinical mutational profiling of bone metastases of lung and colon carcinoma and malignant melanoma using next-generation sequencing. Cancer 124:744–753
Spritzer CE, Afonso PD, Vinson EN et al (2013) Bone marrow biopsy: RNA isolation with expression profiling in men with metastatic castration-resistant prostate cancer–factors affecting diagnostic success. Radiology 269:816–823
Ross RW, Halabi S, Ou SS et al Cancer and Leukemia Group B(2005) Predictors of prostate cancer tissue acquisition by an undirected core bone marrow biopsy in metastatic castration-resistant prostate cancer-a Cancer and Leukemia Group B study. Clin Cancer Res 11:8109–8113
FDA (2020) LYNPARZA (olaparib) prescribing information. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/208558s014lbl.pdf
EMA (2020) LYNPARZA (olaparib) summary of product characteristics. Available from: https://www.ema.europa.eu/en/documents/product-information/lynparzaepar-product-information_en.pdf
de Bono J, Mateo J, Fizazi K et al (2020) Olaparib for metastatic castration-resistant prostate cancer. N Engl J Med 382:2091–2102
Hussain M, Mateo J, Fizazi K et al (2020) Survival with olaparib in metastatic castration-resistant prostate cancer. N Engl J Med 383:2345–2357
Hussain M, Corcoran C, Sibilla C et al (2022) Tumor Genomic Testing for >4,000 Men with Metastatic Castration-resistant Prostate Cancer in the Phase III Trial PROfound (Olaparib). Clin Cancer Res 28(8):1518–1530. https://doi.org/10.1158/1078-0432.CCR-21-3940
Al-Kateb H, Nguyen TT, Steger-May K, Pfeifer JD (2015) Identification of major factors associated with failed clinical molecular oncology testing performed by next generation sequencing (NGS). Mol Oncol 9:1737–1743
Saad F, Armstrong AJ, Thiery-Vuilleminet A et al (2022) Biomarker analysis and updated results from the Phase III PROpel trial of abiraterone (abi) and olaparib (ola) vs abi and placebo (pbo) as first-line (1L) therapy for patients (pts) with metastatic castration-resistant prostate cancer (mCRPC). Ann Oncol 33(suppl_7):S616–S652. https://doi.org/10.1016/annonc/annonc1070
Mateo J, Porta N, Bianchini D et al (2020) Olaparib in patients with metastatic castration-resistant prostate cancer with DNA repair gene aberrations (TOPARP-B): a multicentre, open-label, randomised, phase 2 trial. Lancet Oncol 21(1):162–174
Abida W, Patnaik A, Campbell D et al (2020) Rucaparib in Men With Metastatic Castration-Resistant Prostate Cancer Harboring a BRCA1 or BRCA2 Gene Alteration. J Clin Oncol 38(32):3763–3772
Smith MR, Scher HI, Sandhu S et al (2022) Niraparib in patients with metastatic castration-resistant prostate cancer and DNA repair gene defects (GALAHAD): a multicentre, open-label, phase 2 trial. Lancet Oncol 23:362–373
de Bono JS, Mehra N, Scagliotti GV et al (2022) Talazoparib monotherapy in metastatic castration-resistant prostate cancer with DNA repair alterations (TALAPRO-1): an open-label, phase 2 trial. Lancet Oncol 22(9):1250–1264. https://doi.org/10.1016/S1470-2045(21)00376-4 Erratum in: Lancet Oncol. 23(5):e207. Erratum in: Lancet Oncol. 2022;23(6):e249
Fizazi K, Piulats JM, Reaume MN et al (2023) Rucaparib or Physician's Choice in Metastatic Prostate Cancer. N Engl J Med. https://doi.org/10.1056/NEJMoa2214676
Clarke NW, Armstrong AJ, Thiery-Vuillemin A et al (2022) Abiraterone and olaparib for metastatic castration-resistant prostate cancer. NEJM Evid 1
Chi KN, Rathkopf DE, Smith MR et al (2022) Phase 3 MAGNITUDE study: First results of niraparib (NIRA) with abiraterone acetate and prednisone (AAP) as first-line therapy in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) with and without homologous recombination repair (HRR) gene alterations. J Clin Oncol 40:12
Schweizer MT, Sivakumar S, Tukachinsky H et al (2021) Concordance of DNA Repair Gene Mutations in Paired Primary Prostate Cancer Samples and Metastatic Tissue or Cell-Free DNA. JAMA Oncol 7(9):1–5. https://doi.org/10.1001/jamaoncol.2021.2350
Gandaglia G, Abdollah F, Schiffmann J et al (2014) Distribution of metastatic sites in patients with prostate cancer: A population based analysis. Prostate 74:210–216
Hau A, Kim I, Kattapuram S et al (2002) Accuracy of CT-guided biopsies in 359 patients with musculoskeletal lesions. Skelet Radiol 31:349–353
Shaikh H, Thawani J, Pukenas B (2014) Needle-in-needle technique for percutaneous retrieval of a fractured biopsy needle during CT-guided biopsy of the thoracic spine. Interv Neuroradiol 20:646–649
Luining WI, Meijer D, Dahele MR, Vis AN, Oprea-Lager DE (2021) Nuclear Imaging for Bone Metastases in Prostate Cancer: The Emergence of Modern Techniques Using Novel Radiotracers. Diagnostics (Basel) 11(1):117. https://doi.org/10.3390/diagnostics11010117
Zacho HD, Ravn S, Afshar-Oromieh A et al (2020) Added value of 68Ga-PSMA PET/CT for the detection of bone metastases in patients with newly diagnosed prostate cancer and a previous 99mTc bone scintigraphy. EJNMMI Res 10(1):31. https://doi.org/10.1186/s13550-020-00618-0
Tomasian A, Hillen TJ, Jennings JW (2020) Bone Biopsies: What Radiologists Need to Know. AJR Am J Roentgenol 215(3):523–533
Sailer V, Schiffman MH, Kossai M et al (2018) Bone biopsy protocol for advanced prostate cancer in the era of precision medicine. Cancer 124(5):1008–1015
Garnon J, Koch G, Tsoumakidou G et al (2017) Ultrasound-Guided Biopsies of Bone Lesions Without Cortical Disruption Using Fusion Imaging and Needle Tracking: Proof of Concept. Cardiovasc Intervent Radiol 40(8):1267–1273
Tselikas L, Joskin J, Roquet F et al (2015) Percutaneous bone biopsies: comparison between flat-panel cone-beam CT and CT-scan guidance. Cardiovasc Intervent Radiol 38(1):167–176
Lorente D, Omlin A, Zafeiriou Z et al (2016) Castration-Resistant Prostate Cancer Tissue Acquisition From Bone Metastases for Molecular Analyses. Clin Genitourin Cancer 14(6):485–493. https://doi.org/10.1016/j.clgc.2016.04.016
Suh CH, Yun SJ (2019) Diagnostic Outcome of Image-Guided Percutaneous Core Needle Biopsy of Sclerotic Bone Lesions: A Meta-Analysis. AJR Am J Roentgenol 212(3):625–631
Yang SY, Oh E, Kwon JW, Kim HS (2018) Percutaneous Image-Guided Spinal Lesion Biopsies: Factors Affecting Higher Diagnostic Yield. AJR Am J Roentgenol 211(5):1068–1074
Craig JC, Freeman M, Walton S et al (2022) A Quality Analysis of Bony Specimens for Optimal Ethylenediaminetetraacetic Acid (EDTA) Decalcification. Int J Surg Pathol 30(8):853–860. https://doi.org/10.1177/10668969221088877
Singh VM, Salunga RC, Huang VJ et al (2013) Analysis of the effect of various decalcification agents on the quantity and quality of nucleic acid (DNA and RNA) recovered from bone biopsies. Ann Diagn Pathol 17(4):322–326. https://doi.org/10.1016/j.anndiagpath.2013.02.001
Chen H, Luthra R, Goswami RS et al (2015) Analysis of Pre-Analytic Factors Affecting the Success of Clinical Next-Generation Sequencing of Solid Organ Malignancies. Cancers (Basel) 7(3):1699–1715. https://doi.org/10.3390/cancers7030859
Torlakovic EE, Brynes RK, Hyjek E et al International Council for Standardization in Haematology(2015) ICSH guidelines for the standardization of bone marrow immunohistochemistry. Int J Lab Hematol 37(4):431–449. https://doi.org/10.1111/ijlh.12365
Goswami RS, Luthra R, Singh RR et al (2016) Identification of Factors Affecting the Success of Next-Generation Sequencing Testing in Solid Tumors. Am J Clin Pathol 145:222–237
Saraji A, Offermann A, Stegmann-Frehse J et al (2021) Cracking it - successful mRNA extraction for digital gene expression analysis from decalcified, formalin-fixed and paraffin-embedded bone tissue. PLoS One 16(9):e0257416. https://doi.org/10.1371/journal.pone.0257416
Confavreux CB, Girard N, Pialat JB et al (2014) Mutational profiling of bone metastases from lung adenocarcinoma: results of a prospective study (POUMOS-TEC). Bonekey Rep 3:580. https://doi.org/10.1038/bonekey.2014.75
Tukachinsky H, Madison RW, Chung JH et al (2021) Genomic Analysis of Circulating Tumor DNA in 3,334 Patients with Advanced Prostate Cancer Identifies Targetable BRCA Alterations and AR Resistance Mechanisms. Clin Cancer Res 27(11):3094–3105. https://doi.org/10.1158/1078-0432.CCR-20-4805
Cimadamore A, Cheng L, Massari F et al (2021) Circulating Tumor DNA Testing for Homology Recombination Repair Genes in Prostate Cancer: From the Lab to the Clinic. Int J Mol Sci 22(11):5522. https://doi.org/10.3390/ijms22115522
Chi KN, Barnicle A, Sibilla C et al (2023) Detection of BRCA1, BRCA2, and ATM Alterations in Matched Tumor Tissue and Circulating Tumor DNA in Patients with Prostate Cancer Screened in PROfound. Clin Cancer Res 29(1):81–91. https://doi.org/10.1158/1078-0432.CCR-22-0931
Carreira S, Porta N, Arce-Gallego S et al (2021) Biomarkers Associating with PARP Inhibitor Benefit in Prostate Cancer in the TOPARP-B Trial. Cancer Discov 11(11):2812–2827. https://doi.org/10.1158/2159-8290.CD-21-0007
Jensen K, Konnick EQ, Schweizer MT et al (2021) Association of Clonal Hematopoiesis in DNA Repair Genes With Prostate Cancer Plasma Cell-free DNA Testing Interference. JAMA Oncol 7:107–110. https://doi.org/10.1001/jamaoncol.2020.5161
Forbes C, Fayter D, de Kock S, Quek RG (2019) A systematic review of international guidelines and recommendations for the genetic screening, diagnosis, genetic counseling, and treatment of BRCAmutated breast cancer. Cancer Manag Res 11:2321–2337
Ellison G, Huang S, Carr H et al (2015) A reliable method for the detection of BRCA1 and BRCA2 mutations in fixed tumour tissue utilising multiplex PCR-based targeted next generation sequencing. BMC Clin Pathol 15:5. https://doi.org/10.1186/s12907-015-0004-6
Arreaza G, Qiu P, Pang L et al (2016) Pre-Analytical Considerations for Successful Next-Generation Sequencing (NGS): Challenges and Opportunities for Formalin-Fixed and Paraffin-Embedded Tumor Tissue (FFPE) Samples. Int J Mol Sci 17(9):1579. https://doi.org/10.3390/ijms17091579
Gargis AS, Kalman L, Berry MW et al (2012) Assuring the quality of next-generation sequencing in clinical laboratory practice. Nat Biotechnol 30:1033–1036
Enyedi MZ, Jaksa G, Pintér L et al (2016) Simultaneous detection of BRCA mutations and large genomic rearrangements in germline DNA and FFPE tumor samples. Oncotarget 7:61845–61859
Loman NJ, Misra RV, Dallman TJ et al (2012) Performance comparison of benchtop high-throughput sequencing platforms. Nat Biotechnol 30:434–439
Samorodnitsky E, Jewell BM, Hagopian R et al (2015) Evaluation of Hybridization Capture Versus Amplicon-Based Methods for Whole-Exome Sequencing. Hum Mutat 36(9):903–914. https://doi.org/10.1002/humu.22825
Frampton GM, Fichtenholtz A, Otto GA et al (2013) Development and validation of a clinical cancer genomic profiling test based on massively parallel DNA sequencing. Nat Biotechnol 31:1023–1031
Società Italiana di Genetica Umana Italian Society of Human Genetic Linee di indirizzo sull’analisi dei geni BRCA1 e BRCA2 in ambito clinico https://sigu.net › wp-content › uploads › 2021/03
Feng W, Zhao S, Xue D et al (2016) Improving alignment accuracy on homopolymer regions for semiconductor-based sequencing technologies. BMC Genom 17(Suppl 7):521
Jennings LJ, Arcila ME, Corless C et al (2017) Guidelines for Validation of Next-Generation Sequencing-Based Oncology Panels: A Joint Consensus Recommendation of the Association for Molecular Pathology and College of American Pathologists. J Mol Diagn 19:341–365
Tavtigian SV, Greenblatt MS, Goldgar DE, Boffetta P Group IUGVW(2008) Assessing pathogenicity: overview of results from the IARC Unclassified Genetic Variants Working Group. Hum Mutat 29:1261–1264
Matthijs G, Souche E, Alders M et al (2016) EuroGentest, European Society of Human G. Guidelines for diagnostic next-generation sequencing. Eur J Hum Genet 24:2–5
Vos JR, Fakkert IE, de Hullu JA et al (2020) Universal Tumor DNA BRCA1/2 Testing of Ovarian Cancer: Prescreening PARPi Treatment and Genetic Predisposition. J Natl Cancer Inst 112:161–169
Plon SE, Eccles DM, Easton D et al IARC Unclassified Genetic Variants Working Group(2008) Sequence variant classification and reporting: recommendations for improving the interpretation of cancer susceptibility genetic test results. Hum Mutat 29(11):1282–1291. https://doi.org/10.1002/humu.20880
Author information
Authors and Affiliations
Consortia
Contributions
All authors contributed to data collection, drafting, writing, and editing of the manuscript. Alessia Cimadamore and Sergio Bracarda contributed to study conception and design. All authors read and approved the final manuscript.
Corresponding author
Ethics declarations
Ethics approval
The present research work was conducted according to Ethical Standards. The research did not involve human participants and/or animals.
Conflict of interest
The authors declare no competing interests.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Cimadamore, A., Rescigno, P., Conteduca, V. et al. SIUrO best practice recommendations to optimize BRCA 1/2 gene testing from DNA extracted from bone biopsy in mCRPC patients (BRCA Optimal Bone Biopsy Procedure: BOP). Virchows Arch 483, 579–589 (2023). https://doi.org/10.1007/s00428-023-03660-0
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00428-023-03660-0