The Prognostic Role of MYC Structural Variants Identified by NGS and FISH in Multiple Myeloma
| Autor: | Nadine Abdallah, Shaji Kumar, Jess F. Peterson, Neeraj Sharma, Yan W. Asmann, P. Leif Bergsagel, Patricia T. Greipp, Cinthya Zepeda-Mendoza, Kathryn E. Pearce, S. Vincent Rajkumar, Moritz Binder, Rhett P. Ketterling, James B. Smadbeck, Linda B. Baughn |
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| Rok vydání: | 2021 |
| Předmět: |
Cancer Research
medicine.diagnostic_test Clone (cell biology) Genes myc High-Throughput Nucleotide Sequencing Immunoglobulins Disease Biology medicine.disease Prognosis DNA sequencing Article Oncology Gene expression medicine Cancer research Fish Humans Multiple Myeloma Gene Multiple myeloma Fluorescence in situ hybridization Retrospective Studies |
| Zdroj: | Clin Cancer Res |
| ISSN: | 1557-3265 |
| Popis: | Purpose: Structural variants (SV) of the MYC gene region are common in multiple myeloma and influence disease progression. However, the prognostic significance of different MYC SVs in multiple myeloma has not been clearly established. Experimental Design: We conducted a retrospective study of multiple myeloma comparing MYC SV subtypes identified by next-generation sequencing (NGS) and FISH to MYC expression and disease survival using 140 cases from Mayo Clinic and 658 cases from the MMRF CoMMpass study. Results: MYC SVs were found in 41% of cases and were classified into nine subtypes. A correlation between the presence of a MYC SV and increased MYC expression was identified. Among the nine MYC subtypes, the non-immunoglobulin (non-Ig) insertion subtype was independently associated with improved outcomes, while the Ig insertion subtype, specifically involving the IgL gene partner, was independently associated with poorer outcomes compared with other MYC SV subtypes. Although the FISH methodology failed to detect approximately 70% of all MYC SVs, those detected by FISH were associated with elevated MYC gene expression and poor outcomes suggesting a different pathogenic role for FISH-detected MYC subtypes compared with other MYC subtypes. Conclusions: Understanding the impact of different MYC SVs on disease outcome is necessary for the reliable interpretation of MYC SVs in multiple myeloma. NGS approaches should be considered as a replacement technique for a more comprehensive evaluation of the multiple myeloma clone. |
| Databáze: | OpenAIRE |
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