Genetic Stability of Driver Alterations in Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type and Their Relapses: A Rationale for the Use of Molecular-Based Methods for More Effective Disease Monitoring
Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT) is a rare, aggressive cutaneous lymphoma with a 5-year disease-specific survival of only ~55%. Despite high response rates to initial immune-polychemotherapy, most patients experience a disease relapse. The genetic evolution of p...
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MDPI AG
2022-10-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/20/5152 |
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| author | Anne M. R. Schrader Ruben A. L. de Groen Rein Willemze Patty M. Jansen Koen D. Quint Arjen H. G. Cleven Tom van Wezel Ronald van Eijk Dina Ruano J. Hendrik Veelken Cornelis P. Tensen Karen J. Neelis Laurien A. Daniels Esther Hauben F. J. Sherida H. Woei-A-Jin Anne-Marie Busschots Maarten H. Vermeer Joost S. P. Vermaat |
| author_facet | Anne M. R. Schrader Ruben A. L. de Groen Rein Willemze Patty M. Jansen Koen D. Quint Arjen H. G. Cleven Tom van Wezel Ronald van Eijk Dina Ruano J. Hendrik Veelken Cornelis P. Tensen Karen J. Neelis Laurien A. Daniels Esther Hauben F. J. Sherida H. Woei-A-Jin Anne-Marie Busschots Maarten H. Vermeer Joost S. P. Vermaat |
| author_sort | Anne M. R. Schrader |
| collection | DOAJ |
| description | Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT) is a rare, aggressive cutaneous lymphoma with a 5-year disease-specific survival of only ~55%. Despite high response rates to initial immune-polychemotherapy, most patients experience a disease relapse. The genetic evolution of primary and relapsed/refractory disease has only scarcely been studied in PCDLBCL-LT patients. Therefore, in this retrospective cohort study, 73 primary/pre-treatment and relapsed/refractory biopsies of 57 patients with PCDLBCL-LT were molecularly characterized with triple FISH and targeted next-generation sequencing for 52 B-cell-lymphoma-relevant genes, including paired analysis in 16 patients. In this cohort, 95% of patients harboured at least one of the three main driver alterations (mutations in <i>MYD88</i>/<i>CD79B</i> and/or <i>CDKN2A</i>-loss). In relapsed/refractory PCDLBCL-LT, these oncogenic aberrations were persistently present, demonstrating genetic stability over time. Novel alterations in relapsed disease affected mostly <i>CDKN2A</i>, <i>MYC</i>, and <i>PIM1</i>. Regarding survival, only <i>MYC</i> rearrangements and <i>HIST1H1E</i> mutations were statistically significantly associated with an inferior outcome. The stable presence of one or more of the three main driver alterations (mutated <i>MYD88</i>/<i>CD79B</i> and/or <i>CDKN2A</i>-loss) is promising for targeted therapies addressing these alterations and serves as a rationale for molecular-based disease monitoring, improving response evaluation and early identification and intervention of disease relapses in these poor-prognostic PCDLBCL-LT patients. |
| first_indexed | 2024-03-09T20:31:25Z |
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| issn | 2072-6694 |
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| last_indexed | 2024-03-09T20:31:25Z |
| publishDate | 2022-10-01 |
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| spelling | doaj.art-c52520128e2546c9bb12a06bf359802b2023-11-23T23:22:49ZengMDPI AGCancers2072-66942022-10-011420515210.3390/cancers14205152Genetic Stability of Driver Alterations in Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type and Their Relapses: A Rationale for the Use of Molecular-Based Methods for More Effective Disease MonitoringAnne M. R. Schrader0Ruben A. L. de Groen1Rein Willemze2Patty M. Jansen3Koen D. Quint4Arjen H. G. Cleven5Tom van Wezel6Ronald van Eijk7Dina Ruano8J. Hendrik Veelken9Cornelis P. Tensen10Karen J. Neelis11Laurien A. Daniels12Esther Hauben13F. J. Sherida H. Woei-A-Jin14Anne-Marie Busschots15Maarten H. Vermeer16Joost S. P. Vermaat17Department of Pathology, Leiden University Medical Center, 2333 ZA Leiden, The NetherlandsDepartment of Hematology, Leiden University Medical Center, 2333 ZA Leiden, The NetherlandsDepartment of Dermatology, Leiden University Medical Center, 2333 ZA Leiden, The NetherlandsDepartment of Pathology, Leiden University Medical Center, 2333 ZA Leiden, The NetherlandsDepartment of Dermatology, Leiden University Medical Center, 2333 ZA Leiden, The NetherlandsDepartment of Pathology, Leiden University Medical Center, 2333 ZA Leiden, The NetherlandsDepartment of Pathology, Leiden University Medical Center, 2333 ZA Leiden, The NetherlandsDepartment of Pathology, Leiden University Medical Center, 2333 ZA Leiden, The NetherlandsDepartment of Pathology, Leiden University Medical Center, 2333 ZA Leiden, The NetherlandsDepartment of Hematology, Leiden University Medical Center, 2333 ZA Leiden, The NetherlandsDepartment of Dermatology, Leiden University Medical Center, 2333 ZA Leiden, The NetherlandsDepartment of Radiotherapy, Leiden University Medical Center, 2333 ZA Leiden, The NetherlandsDepartment of Radiotherapy, Leiden University Medical Center, 2333 ZA Leiden, The NetherlandsDepartment of Pathology, University Hospitals Leuven, 3000 Leuven, BelgiumDepartment of General Medical Oncology, University Hospitals Leuven, 3000 Leuven, BelgiumDepartment of Dermatology, University Hospitals Leuven, 3000 Leuven, BelgiumDepartment of Dermatology, Leiden University Medical Center, 2333 ZA Leiden, The NetherlandsDepartment of Hematology, Leiden University Medical Center, 2333 ZA Leiden, The NetherlandsPrimary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT) is a rare, aggressive cutaneous lymphoma with a 5-year disease-specific survival of only ~55%. Despite high response rates to initial immune-polychemotherapy, most patients experience a disease relapse. The genetic evolution of primary and relapsed/refractory disease has only scarcely been studied in PCDLBCL-LT patients. Therefore, in this retrospective cohort study, 73 primary/pre-treatment and relapsed/refractory biopsies of 57 patients with PCDLBCL-LT were molecularly characterized with triple FISH and targeted next-generation sequencing for 52 B-cell-lymphoma-relevant genes, including paired analysis in 16 patients. In this cohort, 95% of patients harboured at least one of the three main driver alterations (mutations in <i>MYD88</i>/<i>CD79B</i> and/or <i>CDKN2A</i>-loss). In relapsed/refractory PCDLBCL-LT, these oncogenic aberrations were persistently present, demonstrating genetic stability over time. Novel alterations in relapsed disease affected mostly <i>CDKN2A</i>, <i>MYC</i>, and <i>PIM1</i>. Regarding survival, only <i>MYC</i> rearrangements and <i>HIST1H1E</i> mutations were statistically significantly associated with an inferior outcome. The stable presence of one or more of the three main driver alterations (mutated <i>MYD88</i>/<i>CD79B</i> and/or <i>CDKN2A</i>-loss) is promising for targeted therapies addressing these alterations and serves as a rationale for molecular-based disease monitoring, improving response evaluation and early identification and intervention of disease relapses in these poor-prognostic PCDLBCL-LT patients.https://www.mdpi.com/2072-6694/14/20/5152primary cutaneous diffuse large B-cell lymphomaleg typegenetic stabilitysurvivaltargeted therapiesliquid biopsies |
| spellingShingle | Anne M. R. Schrader Ruben A. L. de Groen Rein Willemze Patty M. Jansen Koen D. Quint Arjen H. G. Cleven Tom van Wezel Ronald van Eijk Dina Ruano J. Hendrik Veelken Cornelis P. Tensen Karen J. Neelis Laurien A. Daniels Esther Hauben F. J. Sherida H. Woei-A-Jin Anne-Marie Busschots Maarten H. Vermeer Joost S. P. Vermaat Genetic Stability of Driver Alterations in Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type and Their Relapses: A Rationale for the Use of Molecular-Based Methods for More Effective Disease Monitoring Cancers primary cutaneous diffuse large B-cell lymphoma leg type genetic stability survival targeted therapies liquid biopsies |
| title | Genetic Stability of Driver Alterations in Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type and Their Relapses: A Rationale for the Use of Molecular-Based Methods for More Effective Disease Monitoring |
| title_full | Genetic Stability of Driver Alterations in Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type and Their Relapses: A Rationale for the Use of Molecular-Based Methods for More Effective Disease Monitoring |
| title_fullStr | Genetic Stability of Driver Alterations in Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type and Their Relapses: A Rationale for the Use of Molecular-Based Methods for More Effective Disease Monitoring |
| title_full_unstemmed | Genetic Stability of Driver Alterations in Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type and Their Relapses: A Rationale for the Use of Molecular-Based Methods for More Effective Disease Monitoring |
| title_short | Genetic Stability of Driver Alterations in Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type and Their Relapses: A Rationale for the Use of Molecular-Based Methods for More Effective Disease Monitoring |
| title_sort | genetic stability of driver alterations in primary cutaneous diffuse large b cell lymphoma leg type and their relapses a rationale for the use of molecular based methods for more effective disease monitoring |
| topic | primary cutaneous diffuse large B-cell lymphoma leg type genetic stability survival targeted therapies liquid biopsies |
| url | https://www.mdpi.com/2072-6694/14/20/5152 |
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