Chromothripsis in Treatment Resistance in Multiple Myeloma
Multiple myeloma (MM) is a malignant disease caused by an abnormal proliferation of plasma cells, of which the prognostic factors include chromosomal abnormality, β-2 microglobulin, and albumin. Recently, the term chromothripsis has emerged, which is the massive but highly localized chromosomal rear...
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BioMed Central
2017-09-01
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| Series: | Genomics & Informatics |
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| Online Access: | http://genominfo.org/upload/pdf/GI-2017-15-3-87.pdf |
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| author | Kyoung Joo Lee Ki Hong Lee Kyong-Ah Yoon Ji Yeon Sohn Eunyoung Lee Hyewon Lee Hyeon-Seok Eom Sun-Young Kong |
| author_facet | Kyoung Joo Lee Ki Hong Lee Kyong-Ah Yoon Ji Yeon Sohn Eunyoung Lee Hyewon Lee Hyeon-Seok Eom Sun-Young Kong |
| author_sort | Kyoung Joo Lee |
| collection | DOAJ |
| description | Multiple myeloma (MM) is a malignant disease caused by an abnormal proliferation of plasma cells, of which the prognostic factors include chromosomal abnormality, β-2 microglobulin, and albumin. Recently, the term chromothripsis has emerged, which is the massive but highly localized chromosomal rearrangement in response to a one-step catastrophic event. Many studies have shown an association of chromothripsis with the prognosis in several cancers; however, few studies have investigated it in MM. Here, we studied the association between chromothripsis-like patterns and treatment resistance or prognosis. First, we analyzed nine MM cell lines (U266, MM.1S, RPMI8226, KMS-11, KMS-12-BM, KMS-12-PE, KMS-28-BM, KMS-28-PE, and NCI-H929) and bone marrow samples of four patients who were diagnosed with MM by next-generation sequencing-based copy number variation analysis. The frequency of the chromothripsis-like pattern was observed in seven cell lines. We analyzed the treatment-induced chromothripsis-like patterns in KMS-12-BM and KMS-12-PE cells. As a result, breakpoints and chromothripsis-like patterns were increased after drug treatment in the relatively resistant KMS-12-BM. We further analyzed the patients’ results according to the therapeutic response, which was divided into sensitive and resistant, as suggested by the International Myeloma Working Group. The chromothripsis-like pattern was more frequently observed in the resistant group. In the sensitive group, the frequency of the chromothripsis-like pattern decreased after treatment, whereas the resistant group showed increased chromothripsis-like patterns after the treatment. These results suggest that the chromothripsis-like pattern is associated with treatment response in MM. |
| format | Article |
| id | doaj-art-108fa73568b140e4ace3ce68a21bcfa9 |
| institution | Kabale University |
| issn | 2234-0742 |
| language | English |
| publishDate | 2017-09-01 |
| publisher | BioMed Central |
| record_format | Article |
| series | Genomics & Informatics |
| spelling | doaj-art-108fa73568b140e4ace3ce68a21bcfa92025-02-02T06:54:52ZengBioMed CentralGenomics & Informatics2234-07422017-09-01153879710.5808/GI.2017.15.3.87489Chromothripsis in Treatment Resistance in Multiple MyelomaKyoung Joo Lee0Ki Hong Lee1Kyong-Ah Yoon2Ji Yeon Sohn3Eunyoung Lee4Hyewon Lee5Hyeon-Seok Eom6Sun-Young Kong7 Department of Cancer Biomedical Science, National Cancer Center Graduate School of Cancer Science and Policy, Goyang 10408, Korea Department of Cancer Biomedical Science, National Cancer Center Graduate School of Cancer Science and Policy, Goyang 10408, Korea College of Veterinary Medicine, Konkuk University, Seoul 05029, Korea Department of Laboratory Medicine, Center for Diagnostic Oncology, Research Institute and Hospital, National Cancer Center, Goyang 10408, Korea Center for Hematologic Malignancy, National Cancer Center, Goyang 10408, Korea Center for Hematologic Malignancy, National Cancer Center, Goyang 10408, Korea Department of Cancer Biomedical Science, National Cancer Center Graduate School of Cancer Science and Policy, Goyang 10408, Korea Department of Cancer Biomedical Science, National Cancer Center Graduate School of Cancer Science and Policy, Goyang 10408, KoreaMultiple myeloma (MM) is a malignant disease caused by an abnormal proliferation of plasma cells, of which the prognostic factors include chromosomal abnormality, β-2 microglobulin, and albumin. Recently, the term chromothripsis has emerged, which is the massive but highly localized chromosomal rearrangement in response to a one-step catastrophic event. Many studies have shown an association of chromothripsis with the prognosis in several cancers; however, few studies have investigated it in MM. Here, we studied the association between chromothripsis-like patterns and treatment resistance or prognosis. First, we analyzed nine MM cell lines (U266, MM.1S, RPMI8226, KMS-11, KMS-12-BM, KMS-12-PE, KMS-28-BM, KMS-28-PE, and NCI-H929) and bone marrow samples of four patients who were diagnosed with MM by next-generation sequencing-based copy number variation analysis. The frequency of the chromothripsis-like pattern was observed in seven cell lines. We analyzed the treatment-induced chromothripsis-like patterns in KMS-12-BM and KMS-12-PE cells. As a result, breakpoints and chromothripsis-like patterns were increased after drug treatment in the relatively resistant KMS-12-BM. We further analyzed the patients’ results according to the therapeutic response, which was divided into sensitive and resistant, as suggested by the International Myeloma Working Group. The chromothripsis-like pattern was more frequently observed in the resistant group. In the sensitive group, the frequency of the chromothripsis-like pattern decreased after treatment, whereas the resistant group showed increased chromothripsis-like patterns after the treatment. These results suggest that the chromothripsis-like pattern is associated with treatment response in MM.http://genominfo.org/upload/pdf/GI-2017-15-3-87.pdfchromothripsisdrug resistancemultiple myeloma |
| spellingShingle | Kyoung Joo Lee Ki Hong Lee Kyong-Ah Yoon Ji Yeon Sohn Eunyoung Lee Hyewon Lee Hyeon-Seok Eom Sun-Young Kong Chromothripsis in Treatment Resistance in Multiple Myeloma Genomics & Informatics chromothripsis drug resistance multiple myeloma |
| title | Chromothripsis in Treatment Resistance in Multiple Myeloma |
| title_full | Chromothripsis in Treatment Resistance in Multiple Myeloma |
| title_fullStr | Chromothripsis in Treatment Resistance in Multiple Myeloma |
| title_full_unstemmed | Chromothripsis in Treatment Resistance in Multiple Myeloma |
| title_short | Chromothripsis in Treatment Resistance in Multiple Myeloma |
| title_sort | chromothripsis in treatment resistance in multiple myeloma |
| topic | chromothripsis drug resistance multiple myeloma |
| url | http://genominfo.org/upload/pdf/GI-2017-15-3-87.pdf |
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