Detection of <i>BRCA1</i>, and <i>BRCA2</i> Alterations in Matched Tumor Tissue and Circulating Cell-Free DNA in Patients with Prostate Cancer in a Real-World Setting
Background: Poly (ADP-ribose) polymerase (PARP) inhibitors are approved for patients with metastatic castration-resistant prostate cancer harboring deleterious or suspected deleterious <i>BRCA1</i> and/or <i>2</i> mutations. Identifying patients with prostate cancer harboring...
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MDPI AG
2022-12-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/10/12/3170 |
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| author | Taylor Ryan McFarland Vinay Mathew Thomas Roberto Nussenzveig Georges Gebrael Nicolas Sayegh Nishita Tripathi Kamal Kant Sahu Divyam Goel Benjamin L. Maughan Deepika Sirohi Neeraj Agarwal Umang Swami |
| author_facet | Taylor Ryan McFarland Vinay Mathew Thomas Roberto Nussenzveig Georges Gebrael Nicolas Sayegh Nishita Tripathi Kamal Kant Sahu Divyam Goel Benjamin L. Maughan Deepika Sirohi Neeraj Agarwal Umang Swami |
| author_sort | Taylor Ryan McFarland |
| collection | DOAJ |
| description | Background: Poly (ADP-ribose) polymerase (PARP) inhibitors are approved for patients with metastatic castration-resistant prostate cancer harboring deleterious or suspected deleterious <i>BRCA1</i> and/or <i>2</i> mutations. Identifying patients with prostate cancer harboring these mutations may be challenging. Circulating cell-free DNA (cfDNA) provides an avenue for an easier detection of these mutations. Herein, we aimed to evaluate the concordance of <i>BRCA</i> mutations in the tumor tissue and cfDNA in patients with metastatic prostate cancer in the real-world setting. Methods: Somatic genomic profiling results were obtained from a clinical cohort of patients at our institution who had at least two samples tested. One of the samples needed to be from either primary or metastatic tissue. Concordance was adjusted to not include mutation types that the cfDNA platforms were not designed to detect. Results: The presence or absence of mutations in the <i>BRCA</i> gene was assessed in a total of 589 samples, including 327 cfDNA samples, from 260 patients with metastatic prostate cancer. The median time between the first test and any subsequent test was 22.8 (0.0–232) months. <i>BRCA</i> mutation was present in the patient’s original prostate tissue in 23 samples (3.9%) of patients. The adjusted concordance between prostate tumor tissue and cfDNA was 97.9% [95% CI, 95.3–99.1%]. The adjusted concordance between metastatic samples and cfDNA was 93.5% [95% CI, 86.4–97.3%]. Of the patients who had a <i>BRCA</i> mutation detected in their prostate tissue, there was a 70% probability of detecting a <i>BRCA</i> mutation in the patient’s cfDNA as well. For patients who did not have a detectable <i>BRCA</i> mutation in their primary prostate tissue, the probability of detecting a subsequent one later in the disease course was less than 0.9%. Conclusion: There is a high level of concordance between tissue and blood for <i>BRCA</i> mutations. Testing cfDNA can provide reliable information on <i>BRCA</i> mutational status and is a viable alternative to solid tissue sequencing when unavailable. The development of a new <i>BRCA</i> mutation later in the disease course is a rare event. |
| first_indexed | 2024-03-09T17:18:04Z |
| format | Article |
| id | doaj.art-41ebdd18609e4ee39eb8a08fe9e5851e |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-09T17:18:04Z |
| publishDate | 2022-12-01 |
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| series | Biomedicines |
| spelling | doaj.art-41ebdd18609e4ee39eb8a08fe9e5851e2023-11-24T13:28:02ZengMDPI AGBiomedicines2227-90592022-12-011012317010.3390/biomedicines10123170Detection of <i>BRCA1</i>, and <i>BRCA2</i> Alterations in Matched Tumor Tissue and Circulating Cell-Free DNA in Patients with Prostate Cancer in a Real-World SettingTaylor Ryan McFarland0Vinay Mathew Thomas1Roberto Nussenzveig2Georges Gebrael3Nicolas Sayegh4Nishita Tripathi5Kamal Kant Sahu6Divyam Goel7Benjamin L. Maughan8Deepika Sirohi9Neeraj Agarwal10Umang Swami11Division of Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USADivision of Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USADigital Diagnostic Foundation, Cedar City, UT 84720, USADivision of Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USADivision of Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USADivision of Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USADivision of Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USADivision of Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USADivision of Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USADivision of Pathology, University of Utah, Salt Lake City, UT 84112, USADivision of Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USADivision of Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USABackground: Poly (ADP-ribose) polymerase (PARP) inhibitors are approved for patients with metastatic castration-resistant prostate cancer harboring deleterious or suspected deleterious <i>BRCA1</i> and/or <i>2</i> mutations. Identifying patients with prostate cancer harboring these mutations may be challenging. Circulating cell-free DNA (cfDNA) provides an avenue for an easier detection of these mutations. Herein, we aimed to evaluate the concordance of <i>BRCA</i> mutations in the tumor tissue and cfDNA in patients with metastatic prostate cancer in the real-world setting. Methods: Somatic genomic profiling results were obtained from a clinical cohort of patients at our institution who had at least two samples tested. One of the samples needed to be from either primary or metastatic tissue. Concordance was adjusted to not include mutation types that the cfDNA platforms were not designed to detect. Results: The presence or absence of mutations in the <i>BRCA</i> gene was assessed in a total of 589 samples, including 327 cfDNA samples, from 260 patients with metastatic prostate cancer. The median time between the first test and any subsequent test was 22.8 (0.0–232) months. <i>BRCA</i> mutation was present in the patient’s original prostate tissue in 23 samples (3.9%) of patients. The adjusted concordance between prostate tumor tissue and cfDNA was 97.9% [95% CI, 95.3–99.1%]. The adjusted concordance between metastatic samples and cfDNA was 93.5% [95% CI, 86.4–97.3%]. Of the patients who had a <i>BRCA</i> mutation detected in their prostate tissue, there was a 70% probability of detecting a <i>BRCA</i> mutation in the patient’s cfDNA as well. For patients who did not have a detectable <i>BRCA</i> mutation in their primary prostate tissue, the probability of detecting a subsequent one later in the disease course was less than 0.9%. Conclusion: There is a high level of concordance between tissue and blood for <i>BRCA</i> mutations. Testing cfDNA can provide reliable information on <i>BRCA</i> mutational status and is a viable alternative to solid tissue sequencing when unavailable. The development of a new <i>BRCA</i> mutation later in the disease course is a rare event.https://www.mdpi.com/2227-9059/10/12/3170metastatic prostate cancerBRCAPARP inhibitorcancer evolutioncfDNAnext-generation sequencing |
| spellingShingle | Taylor Ryan McFarland Vinay Mathew Thomas Roberto Nussenzveig Georges Gebrael Nicolas Sayegh Nishita Tripathi Kamal Kant Sahu Divyam Goel Benjamin L. Maughan Deepika Sirohi Neeraj Agarwal Umang Swami Detection of <i>BRCA1</i>, and <i>BRCA2</i> Alterations in Matched Tumor Tissue and Circulating Cell-Free DNA in Patients with Prostate Cancer in a Real-World Setting Biomedicines metastatic prostate cancer BRCA PARP inhibitor cancer evolution cfDNA next-generation sequencing |
| title | Detection of <i>BRCA1</i>, and <i>BRCA2</i> Alterations in Matched Tumor Tissue and Circulating Cell-Free DNA in Patients with Prostate Cancer in a Real-World Setting |
| title_full | Detection of <i>BRCA1</i>, and <i>BRCA2</i> Alterations in Matched Tumor Tissue and Circulating Cell-Free DNA in Patients with Prostate Cancer in a Real-World Setting |
| title_fullStr | Detection of <i>BRCA1</i>, and <i>BRCA2</i> Alterations in Matched Tumor Tissue and Circulating Cell-Free DNA in Patients with Prostate Cancer in a Real-World Setting |
| title_full_unstemmed | Detection of <i>BRCA1</i>, and <i>BRCA2</i> Alterations in Matched Tumor Tissue and Circulating Cell-Free DNA in Patients with Prostate Cancer in a Real-World Setting |
| title_short | Detection of <i>BRCA1</i>, and <i>BRCA2</i> Alterations in Matched Tumor Tissue and Circulating Cell-Free DNA in Patients with Prostate Cancer in a Real-World Setting |
| title_sort | detection of i brca1 i and i brca2 i alterations in matched tumor tissue and circulating cell free dna in patients with prostate cancer in a real world setting |
| topic | metastatic prostate cancer BRCA PARP inhibitor cancer evolution cfDNA next-generation sequencing |
| url | https://www.mdpi.com/2227-9059/10/12/3170 |
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