The Dynamics of Nucleotide Variants in the Progression from Low–Intermediate Myeloma Precursor Conditions to Multiple Myeloma: Studying Serial Samples with a Targeted Sequencing Approach
Multiple myeloma (MM), or Kahler’s disease, is an incurable plasma cell (PC) cancer in the bone marrow (BM). This malignancy is preceded by one or more asymptomatic precursor conditions, monoclonal gammopathy of undetermined significance (MGUS) and/or smoldering multiple myeloma (SMM). The molecular...
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| Format: | Article |
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MDPI AG
2022-02-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/4/1035 |
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| author | Bénedith Oben Charlotte Cosemans Ellen Geerdens Loes Linsen Kimberly Vanhees Brigitte Maes Koen Theunissen Bert Cruys Marta Lionetti Ingrid Arijs Niccolò Bolli Guy Froyen Jean-Luc Rummens |
| author_facet | Bénedith Oben Charlotte Cosemans Ellen Geerdens Loes Linsen Kimberly Vanhees Brigitte Maes Koen Theunissen Bert Cruys Marta Lionetti Ingrid Arijs Niccolò Bolli Guy Froyen Jean-Luc Rummens |
| author_sort | Bénedith Oben |
| collection | DOAJ |
| description | Multiple myeloma (MM), or Kahler’s disease, is an incurable plasma cell (PC) cancer in the bone marrow (BM). This malignancy is preceded by one or more asymptomatic precursor conditions, monoclonal gammopathy of undetermined significance (MGUS) and/or smoldering multiple myeloma (SMM). The molecular mechanisms and exact cause of this progression are still not completely understood. In this study, the mutational profile underlying the progression from low–intermediate risk myeloma precursor conditions to MM was studied in serial BM smears. A custom capture-based sequencing platform was developed, including 81 myeloma-related genes. The clonal evolution of single nucleotide variants and short insertions and deletions was studied in serial BM smears from 21 progressed precursor patients with a median time of progression of six years. From the 21 patients, four patients had no variation in one of the 81 studied genes. Interestingly, in 16 of the 17 other patients, at least one variant present in MM was also detected in its precursor BM, even years before progression. Here, the variants were present in the pre-stage at a median of 62 months before progression to MM. Studying these paired BM samples contributes to the knowledge of the evolutionary genetic landscape and provides additional insight into the mutational behavior of mutant clones over time throughout progression. |
| first_indexed | 2024-03-09T22:23:20Z |
| format | Article |
| id | doaj.art-a5490cfed74344a89061b314f1830255 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T22:23:20Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-a5490cfed74344a89061b314f18302552023-11-23T19:10:23ZengMDPI AGCancers2072-66942022-02-01144103510.3390/cancers14041035The Dynamics of Nucleotide Variants in the Progression from Low–Intermediate Myeloma Precursor Conditions to Multiple Myeloma: Studying Serial Samples with a Targeted Sequencing ApproachBénedith Oben0Charlotte Cosemans1Ellen Geerdens2Loes Linsen3Kimberly Vanhees4Brigitte Maes5Koen Theunissen6Bert Cruys7Marta Lionetti8Ingrid Arijs9Niccolò Bolli10Guy Froyen11Jean-Luc Rummens12Laboratory Experimental Hematology, Department Clinical Biology, Jessa Hospital, 3500 Hasselt, BelgiumLaboratory Experimental Hematology, Department Clinical Biology, Jessa Hospital, 3500 Hasselt, BelgiumLaboratory Molecular Diagnostics, Department Clinical Biology, Jessa Hospital, 3500 Hasselt, BelgiumLaboratory Experimental Hematology, Department Clinical Biology, Jessa Hospital, 3500 Hasselt, BelgiumFaculty of Medicine and Life Sciences, Hasselt University, 3500 Hasselt, BelgiumLaboratory Molecular Diagnostics, Department Clinical Biology, Jessa Hospital, 3500 Hasselt, BelgiumDepartment Hematology, Jessa Hospital, 3500 Hasselt, BelgiumLaboratory Molecular Diagnostics, Department Clinical Biology, Jessa Hospital, 3500 Hasselt, BelgiumDepartment Oncology and Hemato-Oncology, University of Milan, 20122 Milan, ItalyFaculty of Medicine and Life Sciences, Hasselt University, 3500 Hasselt, BelgiumDepartment Oncology and Hemato-Oncology, University of Milan, 20122 Milan, ItalyFaculty of Medicine and Life Sciences, Hasselt University, 3500 Hasselt, BelgiumLaboratory Experimental Hematology, Department Clinical Biology, Jessa Hospital, 3500 Hasselt, BelgiumMultiple myeloma (MM), or Kahler’s disease, is an incurable plasma cell (PC) cancer in the bone marrow (BM). This malignancy is preceded by one or more asymptomatic precursor conditions, monoclonal gammopathy of undetermined significance (MGUS) and/or smoldering multiple myeloma (SMM). The molecular mechanisms and exact cause of this progression are still not completely understood. In this study, the mutational profile underlying the progression from low–intermediate risk myeloma precursor conditions to MM was studied in serial BM smears. A custom capture-based sequencing platform was developed, including 81 myeloma-related genes. The clonal evolution of single nucleotide variants and short insertions and deletions was studied in serial BM smears from 21 progressed precursor patients with a median time of progression of six years. From the 21 patients, four patients had no variation in one of the 81 studied genes. Interestingly, in 16 of the 17 other patients, at least one variant present in MM was also detected in its precursor BM, even years before progression. Here, the variants were present in the pre-stage at a median of 62 months before progression to MM. Studying these paired BM samples contributes to the knowledge of the evolutionary genetic landscape and provides additional insight into the mutational behavior of mutant clones over time throughout progression.https://www.mdpi.com/2072-6694/14/4/1035multiple myelomamonoclonal gammopathy of undetermined significancesmoldering multiple myelomaprogressiontargeted sequencing |
| spellingShingle | Bénedith Oben Charlotte Cosemans Ellen Geerdens Loes Linsen Kimberly Vanhees Brigitte Maes Koen Theunissen Bert Cruys Marta Lionetti Ingrid Arijs Niccolò Bolli Guy Froyen Jean-Luc Rummens The Dynamics of Nucleotide Variants in the Progression from Low–Intermediate Myeloma Precursor Conditions to Multiple Myeloma: Studying Serial Samples with a Targeted Sequencing Approach Cancers multiple myeloma monoclonal gammopathy of undetermined significance smoldering multiple myeloma progression targeted sequencing |
| title | The Dynamics of Nucleotide Variants in the Progression from Low–Intermediate Myeloma Precursor Conditions to Multiple Myeloma: Studying Serial Samples with a Targeted Sequencing Approach |
| title_full | The Dynamics of Nucleotide Variants in the Progression from Low–Intermediate Myeloma Precursor Conditions to Multiple Myeloma: Studying Serial Samples with a Targeted Sequencing Approach |
| title_fullStr | The Dynamics of Nucleotide Variants in the Progression from Low–Intermediate Myeloma Precursor Conditions to Multiple Myeloma: Studying Serial Samples with a Targeted Sequencing Approach |
| title_full_unstemmed | The Dynamics of Nucleotide Variants in the Progression from Low–Intermediate Myeloma Precursor Conditions to Multiple Myeloma: Studying Serial Samples with a Targeted Sequencing Approach |
| title_short | The Dynamics of Nucleotide Variants in the Progression from Low–Intermediate Myeloma Precursor Conditions to Multiple Myeloma: Studying Serial Samples with a Targeted Sequencing Approach |
| title_sort | dynamics of nucleotide variants in the progression from low intermediate myeloma precursor conditions to multiple myeloma studying serial samples with a targeted sequencing approach |
| topic | multiple myeloma monoclonal gammopathy of undetermined significance smoldering multiple myeloma progression targeted sequencing |
| url | https://www.mdpi.com/2072-6694/14/4/1035 |
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