Genetic Variants Detected Using Cell-Free DNA from Blood and Tumor Samples in Patients with Inflammatory Breast Cancer
We studied genomic alterations in 19 inflammatory breast cancer (IBC) patients with advanced disease using samples of tissue and paired blood serum or plasma (cell-free DNA, cfDNA) by targeted next generation sequencing (NGS). At diagnosis, the disease was triple negative (TN) in eleven patients (57...
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MDPI AG
2020-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/4/1290 |
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| author | Jennifer S. Winn Zachary Hasse Michael Slifker Jianming Pei Sebastian M. Arisi-Fernandez Jacqueline N. Talarchek Elias Obeid Donald A. Baldwin Yulan Gong Eric Ross Massimo Cristofanilli R. Katherine Alpaugh Sandra V. Fernandez |
| author_facet | Jennifer S. Winn Zachary Hasse Michael Slifker Jianming Pei Sebastian M. Arisi-Fernandez Jacqueline N. Talarchek Elias Obeid Donald A. Baldwin Yulan Gong Eric Ross Massimo Cristofanilli R. Katherine Alpaugh Sandra V. Fernandez |
| author_sort | Jennifer S. Winn |
| collection | DOAJ |
| description | We studied genomic alterations in 19 inflammatory breast cancer (IBC) patients with advanced disease using samples of tissue and paired blood serum or plasma (cell-free DNA, cfDNA) by targeted next generation sequencing (NGS). At diagnosis, the disease was triple negative (TN) in eleven patients (57.8%), ER+ Her2- IBC in six patients (31.6%), ER+ Her2+ IBC in one patient (5.3%), and ER- Her2+ IBC in one other patient (5.3%). Pathogenic or likely pathogenic variants were frequently detected in <i>TP53</i> (47.3%), <i>PMS2</i> (26.3%), <i>MRE11</i> (26.3%), <i>RB1</i> (10.5%), <i>BRCA1</i> (10.5%), <i>PTEN</i> (10.5%) and <i>AR</i> (10.5%); other affected genes included <i>PMS1</i>, <i>KMT2C</i>, <i>BRCA2</i>, <i>PALB2</i>, <i>MUTYH</i>, <i>MEN1</i>, <i>MSH2</i>, <i>CHEK2</i>, <i>NCOR1</i>, <i>PIK3CA</i>, <i>ESR1</i> and <i>MAP2K4.</i> In 15 of the 19 patients in which tissue and paired blood were collected at the same time point, 80% of the variants detected in tissue were also detected in the paired cfDNA. Higher concordance between tissue and cfDNA was found for variants with higher allele fraction in tissue (AF<sub>tissue</sub> ≥ 5%). Furthermore, 86% of the variants detected in cfDNA were also detected in paired tissue. Our study suggests that the genetic profile measured in blood cfDNA is complementary to that of tumor tissue in IBC patients. |
| first_indexed | 2024-04-13T05:51:45Z |
| format | Article |
| id | doaj.art-e0a9b470167444e48089901b7401efe4 |
| institution | Directory Open Access Journal |
| issn | 1422-0067 |
| language | English |
| last_indexed | 2024-04-13T05:51:45Z |
| publishDate | 2020-02-01 |
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| spelling | doaj.art-e0a9b470167444e48089901b7401efe42022-12-22T02:59:45ZengMDPI AGInternational Journal of Molecular Sciences1422-00672020-02-01214129010.3390/ijms21041290ijms21041290Genetic Variants Detected Using Cell-Free DNA from Blood and Tumor Samples in Patients with Inflammatory Breast CancerJennifer S. Winn0Zachary Hasse1Michael Slifker2Jianming Pei3Sebastian M. Arisi-Fernandez4Jacqueline N. Talarchek5Elias Obeid6Donald A. Baldwin7Yulan Gong8Eric Ross9Massimo Cristofanilli10R. Katherine Alpaugh11Sandra V. Fernandez12Fox Chase Cancer Center, Philadelphia, PA 19111, USAFox Chase Cancer Center, Philadelphia, PA 19111, USAFox Chase Cancer Center, Philadelphia, PA 19111, USAFox Chase Cancer Center, Philadelphia, PA 19111, USAFox Chase Cancer Center, Philadelphia, PA 19111, USAFox Chase Cancer Center, Philadelphia, PA 19111, USAFox Chase Cancer Center, Philadelphia, PA 19111, USAFox Chase Cancer Center, Philadelphia, PA 19111, USAFox Chase Cancer Center, Philadelphia, PA 19111, USAFox Chase Cancer Center, Philadelphia, PA 19111, USAFox Chase Cancer Center, Philadelphia, PA 19111, USAFox Chase Cancer Center, Philadelphia, PA 19111, USAFox Chase Cancer Center, Philadelphia, PA 19111, USAWe studied genomic alterations in 19 inflammatory breast cancer (IBC) patients with advanced disease using samples of tissue and paired blood serum or plasma (cell-free DNA, cfDNA) by targeted next generation sequencing (NGS). At diagnosis, the disease was triple negative (TN) in eleven patients (57.8%), ER+ Her2- IBC in six patients (31.6%), ER+ Her2+ IBC in one patient (5.3%), and ER- Her2+ IBC in one other patient (5.3%). Pathogenic or likely pathogenic variants were frequently detected in <i>TP53</i> (47.3%), <i>PMS2</i> (26.3%), <i>MRE11</i> (26.3%), <i>RB1</i> (10.5%), <i>BRCA1</i> (10.5%), <i>PTEN</i> (10.5%) and <i>AR</i> (10.5%); other affected genes included <i>PMS1</i>, <i>KMT2C</i>, <i>BRCA2</i>, <i>PALB2</i>, <i>MUTYH</i>, <i>MEN1</i>, <i>MSH2</i>, <i>CHEK2</i>, <i>NCOR1</i>, <i>PIK3CA</i>, <i>ESR1</i> and <i>MAP2K4.</i> In 15 of the 19 patients in which tissue and paired blood were collected at the same time point, 80% of the variants detected in tissue were also detected in the paired cfDNA. Higher concordance between tissue and cfDNA was found for variants with higher allele fraction in tissue (AF<sub>tissue</sub> ≥ 5%). Furthermore, 86% of the variants detected in cfDNA were also detected in paired tissue. Our study suggests that the genetic profile measured in blood cfDNA is complementary to that of tumor tissue in IBC patients.https://www.mdpi.com/1422-0067/21/4/1290inflammatory breast cancer (ibc)cell-free dna (cfdna)next generation sequencing (ngs) |
| spellingShingle | Jennifer S. Winn Zachary Hasse Michael Slifker Jianming Pei Sebastian M. Arisi-Fernandez Jacqueline N. Talarchek Elias Obeid Donald A. Baldwin Yulan Gong Eric Ross Massimo Cristofanilli R. Katherine Alpaugh Sandra V. Fernandez Genetic Variants Detected Using Cell-Free DNA from Blood and Tumor Samples in Patients with Inflammatory Breast Cancer International Journal of Molecular Sciences inflammatory breast cancer (ibc) cell-free dna (cfdna) next generation sequencing (ngs) |
| title | Genetic Variants Detected Using Cell-Free DNA from Blood and Tumor Samples in Patients with Inflammatory Breast Cancer |
| title_full | Genetic Variants Detected Using Cell-Free DNA from Blood and Tumor Samples in Patients with Inflammatory Breast Cancer |
| title_fullStr | Genetic Variants Detected Using Cell-Free DNA from Blood and Tumor Samples in Patients with Inflammatory Breast Cancer |
| title_full_unstemmed | Genetic Variants Detected Using Cell-Free DNA from Blood and Tumor Samples in Patients with Inflammatory Breast Cancer |
| title_short | Genetic Variants Detected Using Cell-Free DNA from Blood and Tumor Samples in Patients with Inflammatory Breast Cancer |
| title_sort | genetic variants detected using cell free dna from blood and tumor samples in patients with inflammatory breast cancer |
| topic | inflammatory breast cancer (ibc) cell-free dna (cfdna) next generation sequencing (ngs) |
| url | https://www.mdpi.com/1422-0067/21/4/1290 |
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