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Bi-allelic inactivation is more prevalent at relapse in multiple myeloma, identifying RB1 as an independent prognostic marker

The purpose of this study is to identify prognostic markers and treatment targets using a clinically certified sequencing panel in multiple myeloma. We performed targeted sequencing of 578 individuals with plasma cell neoplasms using the FoundationOne Heme panel and identified clinically relevant ab...

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Autores principales: Chavan, S S, He, J, Tytarenko, R, Deshpande, S, Patel, P, Bailey, M, Stein, C K, Stephens, O, Weinhold, N, Petty, N, Steward, D, Rasche, L, Bauer, M, Ashby, C, Peterson, E, Ali, S, Ross, J, Miller, V A, Stephens, P, Thanendrarajan, S, Schinke, C, Zangari, M, van Rhee, F, Barlogie, B, Mughal, T I, Davies, F E, Morgan, G J, Walker, B A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5386330/
https://www.ncbi.nlm.nih.gov/pubmed/28234347
http://dx.doi.org/10.1038/bcj.2017.12
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author Chavan, S S
He, J
Tytarenko, R
Deshpande, S
Patel, P
Bailey, M
Stein, C K
Stephens, O
Weinhold, N
Petty, N
Steward, D
Rasche, L
Bauer, M
Ashby, C
Peterson, E
Ali, S
Ross, J
Miller, V A
Stephens, P
Thanendrarajan, S
Schinke, C
Zangari, M
van Rhee, F
Barlogie, B
Mughal, T I
Davies, F E
Morgan, G J
Walker, B A
author_facet Chavan, S S
He, J
Tytarenko, R
Deshpande, S
Patel, P
Bailey, M
Stein, C K
Stephens, O
Weinhold, N
Petty, N
Steward, D
Rasche, L
Bauer, M
Ashby, C
Peterson, E
Ali, S
Ross, J
Miller, V A
Stephens, P
Thanendrarajan, S
Schinke, C
Zangari, M
van Rhee, F
Barlogie, B
Mughal, T I
Davies, F E
Morgan, G J
Walker, B A
author_sort Chavan, S S
collection PubMed
description The purpose of this study is to identify prognostic markers and treatment targets using a clinically certified sequencing panel in multiple myeloma. We performed targeted sequencing of 578 individuals with plasma cell neoplasms using the FoundationOne Heme panel and identified clinically relevant abnormalities and novel prognostic markers. Mutational burden was associated with maf and proliferation gene expression groups, and a high-mutational burden was associated with a poor prognosis. We identified homozygous deletions that were present in multiple myeloma within key genes, including CDKN2C, RB1, TRAF3, BIRC3 and TP53, and that bi-allelic inactivation was significantly enriched at relapse. Alterations in CDKN2C, TP53, RB1 and the t(4;14) were associated with poor prognosis. Alterations in RB1 were predominantly homozygous deletions and were associated with relapse and a poor prognosis which was independent of other genetic markers, including t(4;14), after multivariate analysis. Bi-allelic inactivation of key tumor suppressor genes in myeloma was enriched at relapse, especially in RB1, CDKN2C and TP53 where they have prognostic significance.
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spelling pubmed-53863302017-04-26 Bi-allelic inactivation is more prevalent at relapse in multiple myeloma, identifying RB1 as an independent prognostic marker Chavan, S S He, J Tytarenko, R Deshpande, S Patel, P Bailey, M Stein, C K Stephens, O Weinhold, N Petty, N Steward, D Rasche, L Bauer, M Ashby, C Peterson, E Ali, S Ross, J Miller, V A Stephens, P Thanendrarajan, S Schinke, C Zangari, M van Rhee, F Barlogie, B Mughal, T I Davies, F E Morgan, G J Walker, B A Blood Cancer J Original Article The purpose of this study is to identify prognostic markers and treatment targets using a clinically certified sequencing panel in multiple myeloma. We performed targeted sequencing of 578 individuals with plasma cell neoplasms using the FoundationOne Heme panel and identified clinically relevant abnormalities and novel prognostic markers. Mutational burden was associated with maf and proliferation gene expression groups, and a high-mutational burden was associated with a poor prognosis. We identified homozygous deletions that were present in multiple myeloma within key genes, including CDKN2C, RB1, TRAF3, BIRC3 and TP53, and that bi-allelic inactivation was significantly enriched at relapse. Alterations in CDKN2C, TP53, RB1 and the t(4;14) were associated with poor prognosis. Alterations in RB1 were predominantly homozygous deletions and were associated with relapse and a poor prognosis which was independent of other genetic markers, including t(4;14), after multivariate analysis. Bi-allelic inactivation of key tumor suppressor genes in myeloma was enriched at relapse, especially in RB1, CDKN2C and TP53 where they have prognostic significance. Nature Publishing Group 2017-02 2017-02-24 /pmc/articles/PMC5386330/ /pubmed/28234347 http://dx.doi.org/10.1038/bcj.2017.12 Text en Copyright © 2017 The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Original Article
Chavan, S S
He, J
Tytarenko, R
Deshpande, S
Patel, P
Bailey, M
Stein, C K
Stephens, O
Weinhold, N
Petty, N
Steward, D
Rasche, L
Bauer, M
Ashby, C
Peterson, E
Ali, S
Ross, J
Miller, V A
Stephens, P
Thanendrarajan, S
Schinke, C
Zangari, M
van Rhee, F
Barlogie, B
Mughal, T I
Davies, F E
Morgan, G J
Walker, B A
Bi-allelic inactivation is more prevalent at relapse in multiple myeloma, identifying RB1 as an independent prognostic marker
title Bi-allelic inactivation is more prevalent at relapse in multiple myeloma, identifying RB1 as an independent prognostic marker
title_full Bi-allelic inactivation is more prevalent at relapse in multiple myeloma, identifying RB1 as an independent prognostic marker
title_fullStr Bi-allelic inactivation is more prevalent at relapse in multiple myeloma, identifying RB1 as an independent prognostic marker
title_full_unstemmed Bi-allelic inactivation is more prevalent at relapse in multiple myeloma, identifying RB1 as an independent prognostic marker
title_short Bi-allelic inactivation is more prevalent at relapse in multiple myeloma, identifying RB1 as an independent prognostic marker
title_sort bi-allelic inactivation is more prevalent at relapse in multiple myeloma, identifying rb1 as an independent prognostic marker
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5386330/
https://www.ncbi.nlm.nih.gov/pubmed/28234347
http://dx.doi.org/10.1038/bcj.2017.12
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