Tracking Clonal Evolution of Multiple Myeloma Using Targeted Next-Generation DNA Sequencing
Clonal evolution drives treatment failure in multiple myeloma (MM). Here, we used a custom 372-gene panel to track genetic changes occurring during MM progression at different stages of the disease. A tumor-only targeted next-generation DNA sequencing was performed on 69 samples sequentially collect...
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MDPI AG
2022-07-01
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| Online Access: | https://www.mdpi.com/2227-9059/10/7/1674 |
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| author | Aleksander Salomon-Perzyński Joanna Barankiewicz Marcin Machnicki Irena Misiewicz-Krzemińska Michał Pawlak Sylwia Radomska Agnieszka Krzywdzińska Aleksandra Bluszcz Piotr Stawiński Małgorzata Rydzanicz Natalia Jakacka Iwona Solarska Katarzyna Borg Zofia Spyra-Górny Tomasz Szpila Bartosz Puła Sebastian Grosicki Tomasz Stokłosa Rafał Płoski Ewa Lech-Marańda Jana Jakubikova Krzysztof Jamroziak |
| author_facet | Aleksander Salomon-Perzyński Joanna Barankiewicz Marcin Machnicki Irena Misiewicz-Krzemińska Michał Pawlak Sylwia Radomska Agnieszka Krzywdzińska Aleksandra Bluszcz Piotr Stawiński Małgorzata Rydzanicz Natalia Jakacka Iwona Solarska Katarzyna Borg Zofia Spyra-Górny Tomasz Szpila Bartosz Puła Sebastian Grosicki Tomasz Stokłosa Rafał Płoski Ewa Lech-Marańda Jana Jakubikova Krzysztof Jamroziak |
| author_sort | Aleksander Salomon-Perzyński |
| collection | DOAJ |
| description | Clonal evolution drives treatment failure in multiple myeloma (MM). Here, we used a custom 372-gene panel to track genetic changes occurring during MM progression at different stages of the disease. A tumor-only targeted next-generation DNA sequencing was performed on 69 samples sequentially collected from 30 MM patients. The MAPK/ERK pathway was mostly affected with KRAS mutated in 47% of patients. Acquisition and loss of mutations were observed in 63% and 37% of patients, respectively. Four different patterns of mutation evolution were found: branching-, mutation acquisition-, mutation loss- and a stable mutational pathway. Better response to anti-myeloma therapy was more frequently observed in patients who followed the mutation loss—compared to the mutation acquisition pathway. More than two-thirds of patients had druggable genes mutated (including cases of heavily pre-treated disease). Only 7% of patients had a stable copy number variants profile. Consequently, a redistribution in stages according to R-ISS between the first and paired samples (R-ISS″) was seen. The higher the R-ISS″, the higher the risk of MM progression and death. We provided new insights into the genetics of MM evolution, especially in heavily pre-treated patients. Additionally, we confirmed that redefining R-ISS at MM relapse is of high clinical value. |
| first_indexed | 2024-03-09T03:40:04Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-09T03:40:04Z |
| publishDate | 2022-07-01 |
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| series | Biomedicines |
| spelling | doaj.art-157b567d61334d2ca4fc78ec78d72b722023-12-03T14:42:22ZengMDPI AGBiomedicines2227-90592022-07-01107167410.3390/biomedicines10071674Tracking Clonal Evolution of Multiple Myeloma Using Targeted Next-Generation DNA SequencingAleksander Salomon-Perzyński0Joanna Barankiewicz1Marcin Machnicki2Irena Misiewicz-Krzemińska3Michał Pawlak4Sylwia Radomska5Agnieszka Krzywdzińska6Aleksandra Bluszcz7Piotr Stawiński8Małgorzata Rydzanicz9Natalia Jakacka10Iwona Solarska11Katarzyna Borg12Zofia Spyra-Górny13Tomasz Szpila14Bartosz Puła15Sebastian Grosicki16Tomasz Stokłosa17Rafał Płoski18Ewa Lech-Marańda19Jana Jakubikova20Krzysztof Jamroziak21Department of Hematology, Institute of Hematology and Transfusion Medicine, 02-776 Warsaw, PolandDepartment of Hematology, Institute of Hematology and Transfusion Medicine, 02-776 Warsaw, PolandDepartment of Tumor Biology and Genetics, Medical University of Warsaw, 02-106 Warsaw, PolandDepartment of Experimental Hematology, Institute of Hematology and Transfusion Medicine, 02-776 Warsaw, PolandDepartment of Experimental Hematology, Institute of Hematology and Transfusion Medicine, 02-776 Warsaw, PolandMolecular Biology Laboratory, Department of Diagnostic Hematology, Institute of Hematology and Transfusion Medicine, 02-776 Warsaw, PolandImmunophenotyping Laboratory, Department of Diagnostic Hematology, Institute of Hematology and Transfusion Medicine, 02-776 Warsaw, PolandCytogenetic Laboratory, Department of Diagnostic Hematology, Institute of Hematology and Transfusion Medicine, 02-776 Warsaw, PolandDepartment of Medical Genetics, Medical University of Warsaw, 02-106 Warsaw, PolandDepartment of Medical Genetics, Medical University of Warsaw, 02-106 Warsaw, PolandDepartment of Hematology, Institute of Hematology and Transfusion Medicine, 02-776 Warsaw, PolandMolecular Biology Laboratory, Department of Diagnostic Hematology, Institute of Hematology and Transfusion Medicine, 02-776 Warsaw, PolandCytogenetic Laboratory, Department of Diagnostic Hematology, Institute of Hematology and Transfusion Medicine, 02-776 Warsaw, PolandDepartment of Hematology and Cancer Prevention, Faculty od Health Sciences, Medical University of Silesia in Katowice, 40-055 Katowice, PolandDepartment of Hematology, Institute of Hematology and Transfusion Medicine, 02-776 Warsaw, PolandDepartment of Hematology, Institute of Hematology and Transfusion Medicine, 02-776 Warsaw, PolandDepartment of Hematology and Cancer Prevention, Faculty od Health Sciences, Medical University of Silesia in Katowice, 40-055 Katowice, PolandDepartment of Tumor Biology and Genetics, Medical University of Warsaw, 02-106 Warsaw, PolandDepartment of Medical Genetics, Medical University of Warsaw, 02-106 Warsaw, PolandDepartment of Hematology, Institute of Hematology and Transfusion Medicine, 02-776 Warsaw, PolandDepartment of Tumor Immunology, Biomedical Research Center, Cancer Research Institute, Slovak Academy of Sciences, Dubravska Cesta 9, 84505 Bratislava, SlovakiaDepartment of Hematology, Transplantation and Internal Medicine, Medical University of Warsaw, 02-106 Warsaw, PolandClonal evolution drives treatment failure in multiple myeloma (MM). Here, we used a custom 372-gene panel to track genetic changes occurring during MM progression at different stages of the disease. A tumor-only targeted next-generation DNA sequencing was performed on 69 samples sequentially collected from 30 MM patients. The MAPK/ERK pathway was mostly affected with KRAS mutated in 47% of patients. Acquisition and loss of mutations were observed in 63% and 37% of patients, respectively. Four different patterns of mutation evolution were found: branching-, mutation acquisition-, mutation loss- and a stable mutational pathway. Better response to anti-myeloma therapy was more frequently observed in patients who followed the mutation loss—compared to the mutation acquisition pathway. More than two-thirds of patients had druggable genes mutated (including cases of heavily pre-treated disease). Only 7% of patients had a stable copy number variants profile. Consequently, a redistribution in stages according to R-ISS between the first and paired samples (R-ISS″) was seen. The higher the R-ISS″, the higher the risk of MM progression and death. We provided new insights into the genetics of MM evolution, especially in heavily pre-treated patients. Additionally, we confirmed that redefining R-ISS at MM relapse is of high clinical value.https://www.mdpi.com/2227-9059/10/7/1674clonal evolutionmultiple myelomanext-generation sequencing |
| spellingShingle | Aleksander Salomon-Perzyński Joanna Barankiewicz Marcin Machnicki Irena Misiewicz-Krzemińska Michał Pawlak Sylwia Radomska Agnieszka Krzywdzińska Aleksandra Bluszcz Piotr Stawiński Małgorzata Rydzanicz Natalia Jakacka Iwona Solarska Katarzyna Borg Zofia Spyra-Górny Tomasz Szpila Bartosz Puła Sebastian Grosicki Tomasz Stokłosa Rafał Płoski Ewa Lech-Marańda Jana Jakubikova Krzysztof Jamroziak Tracking Clonal Evolution of Multiple Myeloma Using Targeted Next-Generation DNA Sequencing Biomedicines clonal evolution multiple myeloma next-generation sequencing |
| title | Tracking Clonal Evolution of Multiple Myeloma Using Targeted Next-Generation DNA Sequencing |
| title_full | Tracking Clonal Evolution of Multiple Myeloma Using Targeted Next-Generation DNA Sequencing |
| title_fullStr | Tracking Clonal Evolution of Multiple Myeloma Using Targeted Next-Generation DNA Sequencing |
| title_full_unstemmed | Tracking Clonal Evolution of Multiple Myeloma Using Targeted Next-Generation DNA Sequencing |
| title_short | Tracking Clonal Evolution of Multiple Myeloma Using Targeted Next-Generation DNA Sequencing |
| title_sort | tracking clonal evolution of multiple myeloma using targeted next generation dna sequencing |
| topic | clonal evolution multiple myeloma next-generation sequencing |
| url | https://www.mdpi.com/2227-9059/10/7/1674 |
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