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The Prognostic Role of MYC Structural Variants Identified by NGS and FISH in Multiple Myeloma

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 multip...

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Autores principales: Sharma, Neeraj, Smadbeck, James B., Abdallah, Nadine, Zepeda-Mendoza, Cinthya, Binder, Moritz, Pearce, Kathryn E., Asmann, Yan W., Peterson, Jess F., Ketterling, Rhett P., Greipp, Patricia T., Bergsagel, P. Leif, Rajkumar, S. Vincent, Kumar, Shaji K., Baughn, Linda B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for Cancer Research 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8738776/
https://www.ncbi.nlm.nih.gov/pubmed/34233962
http://dx.doi.org/10.1158/1078-0432.CCR-21-0005
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author Sharma, Neeraj
Smadbeck, James B.
Abdallah, Nadine
Zepeda-Mendoza, Cinthya
Binder, Moritz
Pearce, Kathryn E.
Asmann, Yan W.
Peterson, Jess F.
Ketterling, Rhett P.
Greipp, Patricia T.
Bergsagel, P. Leif
Rajkumar, S. Vincent
Kumar, Shaji K.
Baughn, Linda B.
author_facet Sharma, Neeraj
Smadbeck, James B.
Abdallah, Nadine
Zepeda-Mendoza, Cinthya
Binder, Moritz
Pearce, Kathryn E.
Asmann, Yan W.
Peterson, Jess F.
Ketterling, Rhett P.
Greipp, Patricia T.
Bergsagel, P. Leif
Rajkumar, S. Vincent
Kumar, Shaji K.
Baughn, Linda B.
author_sort Sharma, Neeraj
collection PubMed
description 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.
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spelling pubmed-87387762022-03-27 The Prognostic Role of MYC Structural Variants Identified by NGS and FISH in Multiple Myeloma Sharma, Neeraj Smadbeck, James B. Abdallah, Nadine Zepeda-Mendoza, Cinthya Binder, Moritz Pearce, Kathryn E. Asmann, Yan W. Peterson, Jess F. Ketterling, Rhett P. Greipp, Patricia T. Bergsagel, P. Leif Rajkumar, S. Vincent Kumar, Shaji K. Baughn, Linda B. Clin Cancer Res Translational Cancer Mechanisms and Therapy 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. American Association for Cancer Research 2021-10-01 2021-07-07 /pmc/articles/PMC8738776/ /pubmed/34233962 http://dx.doi.org/10.1158/1078-0432.CCR-21-0005 Text en ©2021 The Authors; Published by the American Association for Cancer Research https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) license.
spellingShingle Translational Cancer Mechanisms and Therapy
Sharma, Neeraj
Smadbeck, James B.
Abdallah, Nadine
Zepeda-Mendoza, Cinthya
Binder, Moritz
Pearce, Kathryn E.
Asmann, Yan W.
Peterson, Jess F.
Ketterling, Rhett P.
Greipp, Patricia T.
Bergsagel, P. Leif
Rajkumar, S. Vincent
Kumar, Shaji K.
Baughn, Linda B.
The Prognostic Role of MYC Structural Variants Identified by NGS and FISH in Multiple Myeloma
title The Prognostic Role of MYC Structural Variants Identified by NGS and FISH in Multiple Myeloma
title_full The Prognostic Role of MYC Structural Variants Identified by NGS and FISH in Multiple Myeloma
title_fullStr The Prognostic Role of MYC Structural Variants Identified by NGS and FISH in Multiple Myeloma
title_full_unstemmed The Prognostic Role of MYC Structural Variants Identified by NGS and FISH in Multiple Myeloma
title_short The Prognostic Role of MYC Structural Variants Identified by NGS and FISH in Multiple Myeloma
title_sort prognostic role of myc structural variants identified by ngs and fish in multiple myeloma
topic Translational Cancer Mechanisms and Therapy
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8738776/
https://www.ncbi.nlm.nih.gov/pubmed/34233962
http://dx.doi.org/10.1158/1078-0432.CCR-21-0005
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