Identification of Genetic Alterations by Circulating Tumor DNA in Leiomyosarcoma: A Molecular Analysis of 73 Patients
Background: Leiomyosarcoma is a malignant mesenchymal tumor of cells of smooth muscle lineage arising commonly in retroperitoneum, uterus, large veins, and the limbs. The genetics of leiomyosarcomas are complex and there is very limited understanding of common driver mutations. Circulating tumor DNA...
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| Format: | Article |
| Language: | English |
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Innovative Healthcare Institute
2020-05-01
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| Series: | Journal of Immunotherapy and Precision Oncology |
| Subjects: | |
| Online Access: | https://jipo.org/doi/pdf/10.36401/JIPO-20-3 |
| _version_ | 1797962761909567488 |
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| author | Junaid Arshad Priscila Barreto-Coelho Emily Jonczak Andrea Espejo Gina D’Amato Jonathan C. Trent |
| author_facet | Junaid Arshad Priscila Barreto-Coelho Emily Jonczak Andrea Espejo Gina D’Amato Jonathan C. Trent |
| author_sort | Junaid Arshad |
| collection | DOAJ |
| description | Background: Leiomyosarcoma is a malignant mesenchymal tumor of cells of smooth muscle lineage arising commonly in retroperitoneum, uterus, large veins, and the limbs. The genetics of leiomyosarcomas are complex and there is very limited understanding of common driver mutations. Circulating tumor DNA (ctDNA) offers a rapid and noninvasive method of next-generation sequencing (NGS) that could be used for diagnosis, therapy, and detection of recurrence. Methods: ctDNA testing was performed using Guardant360, which detects single nucleotide variants, amplifications, fusions, and specific insertion/deletion mutations in 73 genes using NGS. Results: Of 73 patients, 59 were found to have one or more cancer-associated genomic alteration. Forty-five (76%) were female with a median age of 63 (range, 38–87) years. All samples were designated metastatic. The most common alterations were detected in Tp53 (65%), BRAF (13%), CCNE (13%), EGFR (12%), PIK3CA (12%), FGFR1 (10%), RB1(10%), KIT (8%), and PDGFRA (8%). Some of the other alterations included RAF1, ERBB2, MET, PTEN TERT, APC, and NOTCH1. Potentially targetable mutations, by Food and Drug Administration–approved or clinical trials, were found in 24 (40%) of the 73 patients. Four patients (5%) were found to have incidental germline TP53 mutations. Conclusion: NGS of ctDNA allows identification of genomic alterations in plasma from patients with leiomyosarcoma. Unfortunately, there is limited activity of current targeted agents in leiomyosarcomas. These results suggest opportunities to develop therapy against TP53, cell cycle, and kinase signaling pathways. Further validation and prospective evaluation is warranted to investigate the clinical utility of ctDNA for patients with leiomyosarcoma. |
| first_indexed | 2024-04-11T01:17:58Z |
| format | Article |
| id | doaj.art-fc35834872b14921b641ccaa4d7701af |
| institution | Directory Open Access Journal |
| issn | 2666-2345 2590-017X |
| language | English |
| last_indexed | 2024-04-11T01:17:58Z |
| publishDate | 2020-05-01 |
| publisher | Innovative Healthcare Institute |
| record_format | Article |
| series | Journal of Immunotherapy and Precision Oncology |
| spelling | doaj.art-fc35834872b14921b641ccaa4d7701af2023-01-03T19:12:57ZengInnovative Healthcare InstituteJournal of Immunotherapy and Precision Oncology2666-23452590-017X2020-05-01646810.36401/JIPO-20-3i2590-017X-3-2-64Identification of Genetic Alterations by Circulating Tumor DNA in Leiomyosarcoma: A Molecular Analysis of 73 PatientsJunaid Arshad0Priscila Barreto-Coelho1Emily Jonczak2Andrea Espejo3Gina D’Amato4Jonathan C. Trent51 Department of Medicine, Division of Medical Oncology, Miller School of Medicine, Jackson Memorial Hospital/ University of Miami, Miami, FL, USA2 Department of Medicine, Division of Internal Medicine, Miller School of Medicine, Jackson Memorial Hospital/ University of Miami, Miami, FL, USA1 Department of Medicine, Division of Medical Oncology, Miller School of Medicine, Jackson Memorial Hospital/ University of Miami, Miami, FL, USA1 Department of Medicine, Division of Medical Oncology, Miller School of Medicine, Jackson Memorial Hospital/ University of Miami, Miami, FL, USA1 Department of Medicine, Division of Medical Oncology, Miller School of Medicine, Jackson Memorial Hospital/ University of Miami, Miami, FL, USA1 Department of Medicine, Division of Medical Oncology, Miller School of Medicine, Jackson Memorial Hospital/ University of Miami, Miami, FL, USABackground: Leiomyosarcoma is a malignant mesenchymal tumor of cells of smooth muscle lineage arising commonly in retroperitoneum, uterus, large veins, and the limbs. The genetics of leiomyosarcomas are complex and there is very limited understanding of common driver mutations. Circulating tumor DNA (ctDNA) offers a rapid and noninvasive method of next-generation sequencing (NGS) that could be used for diagnosis, therapy, and detection of recurrence. Methods: ctDNA testing was performed using Guardant360, which detects single nucleotide variants, amplifications, fusions, and specific insertion/deletion mutations in 73 genes using NGS. Results: Of 73 patients, 59 were found to have one or more cancer-associated genomic alteration. Forty-five (76%) were female with a median age of 63 (range, 38–87) years. All samples were designated metastatic. The most common alterations were detected in Tp53 (65%), BRAF (13%), CCNE (13%), EGFR (12%), PIK3CA (12%), FGFR1 (10%), RB1(10%), KIT (8%), and PDGFRA (8%). Some of the other alterations included RAF1, ERBB2, MET, PTEN TERT, APC, and NOTCH1. Potentially targetable mutations, by Food and Drug Administration–approved or clinical trials, were found in 24 (40%) of the 73 patients. Four patients (5%) were found to have incidental germline TP53 mutations. Conclusion: NGS of ctDNA allows identification of genomic alterations in plasma from patients with leiomyosarcoma. Unfortunately, there is limited activity of current targeted agents in leiomyosarcomas. These results suggest opportunities to develop therapy against TP53, cell cycle, and kinase signaling pathways. Further validation and prospective evaluation is warranted to investigate the clinical utility of ctDNA for patients with leiomyosarcoma.https://jipo.org/doi/pdf/10.36401/JIPO-20-3ctdnagenetic alterationsleiomyosarcoma |
| spellingShingle | Junaid Arshad Priscila Barreto-Coelho Emily Jonczak Andrea Espejo Gina D’Amato Jonathan C. Trent Identification of Genetic Alterations by Circulating Tumor DNA in Leiomyosarcoma: A Molecular Analysis of 73 Patients Journal of Immunotherapy and Precision Oncology ctdna genetic alterations leiomyosarcoma |
| title | Identification of Genetic Alterations by Circulating Tumor DNA in Leiomyosarcoma: A Molecular Analysis of 73 Patients |
| title_full | Identification of Genetic Alterations by Circulating Tumor DNA in Leiomyosarcoma: A Molecular Analysis of 73 Patients |
| title_fullStr | Identification of Genetic Alterations by Circulating Tumor DNA in Leiomyosarcoma: A Molecular Analysis of 73 Patients |
| title_full_unstemmed | Identification of Genetic Alterations by Circulating Tumor DNA in Leiomyosarcoma: A Molecular Analysis of 73 Patients |
| title_short | Identification of Genetic Alterations by Circulating Tumor DNA in Leiomyosarcoma: A Molecular Analysis of 73 Patients |
| title_sort | identification of genetic alterations by circulating tumor dna in leiomyosarcoma a molecular analysis of 73 patients |
| topic | ctdna genetic alterations leiomyosarcoma |
| url | https://jipo.org/doi/pdf/10.36401/JIPO-20-3 |
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