DNA Sequencing of CD138 Cell Population Reveals TP53 and RAS-MAPK Mutations in Multiple Myeloma at Diagnosis
Multiple myeloma is a hematologic neoplasm caused by abnormal proliferation of plasma cells. Sequencing studies suggest that plasma cell disorders are caused by both cytogenetic abnormalities and oncogene mutations. Therefore, it is necessary to detect molecular abnormalities to improve the diagnosi...
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MDPI AG
2024-01-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/16/2/358 |
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| author | Mihaela Dragomir Onda-Tabita Călugăru Bogdan Popescu Cerasela Jardan Dumitru Jardan Monica Popescu Silvia Aposteanu Sorina Bădeliță Gabriela Nedelcu Cătălin Șerban Codruța Popa Tatiana Vassu-Dimov Daniel Coriu |
| author_facet | Mihaela Dragomir Onda-Tabita Călugăru Bogdan Popescu Cerasela Jardan Dumitru Jardan Monica Popescu Silvia Aposteanu Sorina Bădeliță Gabriela Nedelcu Cătălin Șerban Codruța Popa Tatiana Vassu-Dimov Daniel Coriu |
| author_sort | Mihaela Dragomir |
| collection | DOAJ |
| description | Multiple myeloma is a hematologic neoplasm caused by abnormal proliferation of plasma cells. Sequencing studies suggest that plasma cell disorders are caused by both cytogenetic abnormalities and oncogene mutations. Therefore, it is necessary to detect molecular abnormalities to improve the diagnosis and management of MM. The main purpose of this study is to determine whether NGS, in addition to cytogenetics, can influence risk stratification and management. Additionally, we aim to establish whether mutational analysis of the CD138 cell population is a suitable option for the characterization of MM compared to the bulk population. Following the separation of the plasma cells harvested from 35 patients newly diagnosed with MM, we performed a FISH analysis to detect the most common chromosomal abnormalities. Consecutively, we used NGS to evaluate NRAS, KRAS, BRAF, and TP53 mutations in plasma cell populations and in bone marrow samples. NGS data showed that sequencing CD138 cells provides a more sensitive approach. We identified several variants in BRAF, KRAS, and TP53 that were not previously associated with MM. Considering that the presence of somatic mutations could influence risk stratification and therapeutic approaches of patients with MM, sensitive detection of these mutations at diagnosis is essential for optimal management of MM. |
| first_indexed | 2024-03-08T11:03:17Z |
| format | Article |
| id | doaj.art-6915b1c628934c0abfd89008c3da18a4 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-08T11:03:17Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-6915b1c628934c0abfd89008c3da18a42024-01-26T15:36:26ZengMDPI AGCancers2072-66942024-01-0116235810.3390/cancers16020358DNA Sequencing of CD138 Cell Population Reveals TP53 and RAS-MAPK Mutations in Multiple Myeloma at DiagnosisMihaela Dragomir0Onda-Tabita Călugăru1Bogdan Popescu2Cerasela Jardan3Dumitru Jardan4Monica Popescu5Silvia Aposteanu6Sorina Bădeliță7Gabriela Nedelcu8Cătălin Șerban9Codruța Popa10Tatiana Vassu-Dimov11Daniel Coriu12Faculty of Biology, University of Bucharest, 030018 Bucharest, RomaniaFundeni Clinical Institute, 022328 Bucharest, RomaniaHematology Department, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, RomaniaFundeni Clinical Institute, 022328 Bucharest, RomaniaMolecular Biology Laboratory, Medlife Bucharest, 010093 Bucharest, RomaniaFundeni Clinical Institute, 022328 Bucharest, RomaniaFundeni Clinical Institute, 022328 Bucharest, RomaniaFundeni Clinical Institute, 022328 Bucharest, RomaniaFundeni Clinical Institute, 022328 Bucharest, RomaniaFundeni Clinical Institute, 022328 Bucharest, RomaniaFundeni Clinical Institute, 022328 Bucharest, RomaniaFaculty of Biology, University of Bucharest, 030018 Bucharest, RomaniaFundeni Clinical Institute, 022328 Bucharest, RomaniaMultiple myeloma is a hematologic neoplasm caused by abnormal proliferation of plasma cells. Sequencing studies suggest that plasma cell disorders are caused by both cytogenetic abnormalities and oncogene mutations. Therefore, it is necessary to detect molecular abnormalities to improve the diagnosis and management of MM. The main purpose of this study is to determine whether NGS, in addition to cytogenetics, can influence risk stratification and management. Additionally, we aim to establish whether mutational analysis of the CD138 cell population is a suitable option for the characterization of MM compared to the bulk population. Following the separation of the plasma cells harvested from 35 patients newly diagnosed with MM, we performed a FISH analysis to detect the most common chromosomal abnormalities. Consecutively, we used NGS to evaluate NRAS, KRAS, BRAF, and TP53 mutations in plasma cell populations and in bone marrow samples. NGS data showed that sequencing CD138 cells provides a more sensitive approach. We identified several variants in BRAF, KRAS, and TP53 that were not previously associated with MM. Considering that the presence of somatic mutations could influence risk stratification and therapeutic approaches of patients with MM, sensitive detection of these mutations at diagnosis is essential for optimal management of MM.https://www.mdpi.com/2072-6694/16/2/358multiple myelomaNGSplasma cells |
| spellingShingle | Mihaela Dragomir Onda-Tabita Călugăru Bogdan Popescu Cerasela Jardan Dumitru Jardan Monica Popescu Silvia Aposteanu Sorina Bădeliță Gabriela Nedelcu Cătălin Șerban Codruța Popa Tatiana Vassu-Dimov Daniel Coriu DNA Sequencing of CD138 Cell Population Reveals TP53 and RAS-MAPK Mutations in Multiple Myeloma at Diagnosis Cancers multiple myeloma NGS plasma cells |
| title | DNA Sequencing of CD138 Cell Population Reveals TP53 and RAS-MAPK Mutations in Multiple Myeloma at Diagnosis |
| title_full | DNA Sequencing of CD138 Cell Population Reveals TP53 and RAS-MAPK Mutations in Multiple Myeloma at Diagnosis |
| title_fullStr | DNA Sequencing of CD138 Cell Population Reveals TP53 and RAS-MAPK Mutations in Multiple Myeloma at Diagnosis |
| title_full_unstemmed | DNA Sequencing of CD138 Cell Population Reveals TP53 and RAS-MAPK Mutations in Multiple Myeloma at Diagnosis |
| title_short | DNA Sequencing of CD138 Cell Population Reveals TP53 and RAS-MAPK Mutations in Multiple Myeloma at Diagnosis |
| title_sort | dna sequencing of cd138 cell population reveals tp53 and ras mapk mutations in multiple myeloma at diagnosis |
| topic | multiple myeloma NGS plasma cells |
| url | https://www.mdpi.com/2072-6694/16/2/358 |
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