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Centrosome associated genes pattern for risk sub-stratification in multiple myeloma

BACKGROUND: The genome of multiple myeloma (MM) cells is extremely unstable, characterized by a complex combination of structure and numerical abnormalities. It seems that there are several “myeloma subgroups” which differ in expression profile, clinical manifestations, prognoses and treatment respo...

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Autores principales: Kryukov, Fedor, Nemec, Pavel, Radova, Lenka, Kryukova, Elena, Okubote, Samuel, Minarik, Jiri, Stefanikova, Zdena, Pour, Ludek, Hajek, Roman
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4884414/
https://www.ncbi.nlm.nih.gov/pubmed/27234807
http://dx.doi.org/10.1186/s12967-016-0906-9
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author Kryukov, Fedor
Nemec, Pavel
Radova, Lenka
Kryukova, Elena
Okubote, Samuel
Minarik, Jiri
Stefanikova, Zdena
Pour, Ludek
Hajek, Roman
author_facet Kryukov, Fedor
Nemec, Pavel
Radova, Lenka
Kryukova, Elena
Okubote, Samuel
Minarik, Jiri
Stefanikova, Zdena
Pour, Ludek
Hajek, Roman
author_sort Kryukov, Fedor
collection PubMed
description BACKGROUND: The genome of multiple myeloma (MM) cells is extremely unstable, characterized by a complex combination of structure and numerical abnormalities. It seems that there are several “myeloma subgroups” which differ in expression profile, clinical manifestations, prognoses and treatment response. In our previous work, the list of 35 candidate genes with a known role in carcinogenesis and associated with centrosome structure/function was used as a display of molecular heterogeneity with an impact in myeloma pathogenesis. The current study was devoted to establish a risk stratification model based on the aforementioned candidate genes. METHODS: A total of 151 patients were included in this study. CD138+ cells were separated by magnetic-activated cell sorting (MACS). Gene expression profiling (GEP) and Interphase FISH with cytoplasmic immunoglobulin light chain staining (cIg FISH) were performed on plasma cells (PCs). All statistical analyses were performed using freeware R and its additional packages. Training and validation cohort includes 73 and 78 patients, respectively. RESULTS: We have finally established a model that includes 12 selected genes (centrosome associated gene pattern, CAGP) which appears to be an independent prognostic factor for MM stratification. We have shown that the new CAGP model can sub-stratify prognosis in patients without TP53 loss as well as in IMWG high risk patients’ group. CONCLUSIONS: We assume that newly established risk stratification model complements the current prognostic panel used in multiple myeloma and refines the classification of patients in relation to the disease risks. This approach can be used independently as well as in combination with other factors. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12967-016-0906-9) contains supplementary material, which is available to authorized users.
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spelling pubmed-48844142016-05-29 Centrosome associated genes pattern for risk sub-stratification in multiple myeloma Kryukov, Fedor Nemec, Pavel Radova, Lenka Kryukova, Elena Okubote, Samuel Minarik, Jiri Stefanikova, Zdena Pour, Ludek Hajek, Roman J Transl Med Research BACKGROUND: The genome of multiple myeloma (MM) cells is extremely unstable, characterized by a complex combination of structure and numerical abnormalities. It seems that there are several “myeloma subgroups” which differ in expression profile, clinical manifestations, prognoses and treatment response. In our previous work, the list of 35 candidate genes with a known role in carcinogenesis and associated with centrosome structure/function was used as a display of molecular heterogeneity with an impact in myeloma pathogenesis. The current study was devoted to establish a risk stratification model based on the aforementioned candidate genes. METHODS: A total of 151 patients were included in this study. CD138+ cells were separated by magnetic-activated cell sorting (MACS). Gene expression profiling (GEP) and Interphase FISH with cytoplasmic immunoglobulin light chain staining (cIg FISH) were performed on plasma cells (PCs). All statistical analyses were performed using freeware R and its additional packages. Training and validation cohort includes 73 and 78 patients, respectively. RESULTS: We have finally established a model that includes 12 selected genes (centrosome associated gene pattern, CAGP) which appears to be an independent prognostic factor for MM stratification. We have shown that the new CAGP model can sub-stratify prognosis in patients without TP53 loss as well as in IMWG high risk patients’ group. CONCLUSIONS: We assume that newly established risk stratification model complements the current prognostic panel used in multiple myeloma and refines the classification of patients in relation to the disease risks. This approach can be used independently as well as in combination with other factors. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12967-016-0906-9) contains supplementary material, which is available to authorized users. BioMed Central 2016-05-28 /pmc/articles/PMC4884414/ /pubmed/27234807 http://dx.doi.org/10.1186/s12967-016-0906-9 Text en © The Author(s) 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Kryukov, Fedor
Nemec, Pavel
Radova, Lenka
Kryukova, Elena
Okubote, Samuel
Minarik, Jiri
Stefanikova, Zdena
Pour, Ludek
Hajek, Roman
Centrosome associated genes pattern for risk sub-stratification in multiple myeloma
title Centrosome associated genes pattern for risk sub-stratification in multiple myeloma
title_full Centrosome associated genes pattern for risk sub-stratification in multiple myeloma
title_fullStr Centrosome associated genes pattern for risk sub-stratification in multiple myeloma
title_full_unstemmed Centrosome associated genes pattern for risk sub-stratification in multiple myeloma
title_short Centrosome associated genes pattern for risk sub-stratification in multiple myeloma
title_sort centrosome associated genes pattern for risk sub-stratification in multiple myeloma
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4884414/
https://www.ncbi.nlm.nih.gov/pubmed/27234807
http://dx.doi.org/10.1186/s12967-016-0906-9
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