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Integrated Genomic Analysis of Chromosomal Alterations and Mutations in B-Cell Acute Lymphoblastic Leukemia Reveals Distinct Genetic Profiles at Relapse

The clonal basis of relapse in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is complex and not fully understood. Next-generation sequencing (NGS), array comparative genomic hybridization (aCGH), and multiplex ligation-dependent probe amplification (MLPA) were carried out in matched diagno...

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Autores principales: Forero-Castro, Maribel, Montaño, Adrián, Robledo, Cristina, García de Coca, Alfonso, Fuster, José Luis, de las Heras, Natalia, Queizán, José Antonio, Hernández-Sánchez, María, Corchete-Sánchez, Luis A., Martín-Izquierdo, Marta, Ribera, Jordi, Ribera, José-María, Benito, Rocío, Hernández-Rivas, Jesús M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7400270/
https://www.ncbi.nlm.nih.gov/pubmed/32635531
http://dx.doi.org/10.3390/diagnostics10070455
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author Forero-Castro, Maribel
Montaño, Adrián
Robledo, Cristina
García de Coca, Alfonso
Fuster, José Luis
de las Heras, Natalia
Queizán, José Antonio
Hernández-Sánchez, María
Corchete-Sánchez, Luis A.
Martín-Izquierdo, Marta
Ribera, Jordi
Ribera, José-María
Benito, Rocío
Hernández-Rivas, Jesús M.
author_facet Forero-Castro, Maribel
Montaño, Adrián
Robledo, Cristina
García de Coca, Alfonso
Fuster, José Luis
de las Heras, Natalia
Queizán, José Antonio
Hernández-Sánchez, María
Corchete-Sánchez, Luis A.
Martín-Izquierdo, Marta
Ribera, Jordi
Ribera, José-María
Benito, Rocío
Hernández-Rivas, Jesús M.
author_sort Forero-Castro, Maribel
collection PubMed
description The clonal basis of relapse in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is complex and not fully understood. Next-generation sequencing (NGS), array comparative genomic hybridization (aCGH), and multiplex ligation-dependent probe amplification (MLPA) were carried out in matched diagnosis–relapse samples from 13 BCP-ALL patients to identify patterns of genetic evolution that could account for the phenotypic changes associated with disease relapse. The integrative genomic analysis of aCGH, MLPA and NGS revealed that 100% of the BCP-ALL patients showed at least one genetic alteration at diagnosis and relapse. In addition, there was a significant increase in the frequency of chromosomal lesions at the time of relapse (p = 0.019). MLPA and aCGH techniques showed that IKZF1 was the most frequently deleted gene. TP53 was the most frequently mutated gene at relapse. Two TP53 mutations were detected only at relapse, whereas the three others showed an increase in their mutational burden at relapse. Clonal evolution patterns were heterogeneous, involving the acquisition, loss and maintenance of lesions at relapse. Therefore, this study provides additional evidence that BCP-ALL is a genetically dynamic disease with distinct genetic profiles at diagnosis and relapse. Integrative NGS, aCGH and MLPA analysis enables better molecular characterization of the genetic profile in BCP-ALL patients during the evolution from diagnosis to relapse.
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spelling pubmed-74002702020-08-23 Integrated Genomic Analysis of Chromosomal Alterations and Mutations in B-Cell Acute Lymphoblastic Leukemia Reveals Distinct Genetic Profiles at Relapse Forero-Castro, Maribel Montaño, Adrián Robledo, Cristina García de Coca, Alfonso Fuster, José Luis de las Heras, Natalia Queizán, José Antonio Hernández-Sánchez, María Corchete-Sánchez, Luis A. Martín-Izquierdo, Marta Ribera, Jordi Ribera, José-María Benito, Rocío Hernández-Rivas, Jesús M. Diagnostics (Basel) Article The clonal basis of relapse in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is complex and not fully understood. Next-generation sequencing (NGS), array comparative genomic hybridization (aCGH), and multiplex ligation-dependent probe amplification (MLPA) were carried out in matched diagnosis–relapse samples from 13 BCP-ALL patients to identify patterns of genetic evolution that could account for the phenotypic changes associated with disease relapse. The integrative genomic analysis of aCGH, MLPA and NGS revealed that 100% of the BCP-ALL patients showed at least one genetic alteration at diagnosis and relapse. In addition, there was a significant increase in the frequency of chromosomal lesions at the time of relapse (p = 0.019). MLPA and aCGH techniques showed that IKZF1 was the most frequently deleted gene. TP53 was the most frequently mutated gene at relapse. Two TP53 mutations were detected only at relapse, whereas the three others showed an increase in their mutational burden at relapse. Clonal evolution patterns were heterogeneous, involving the acquisition, loss and maintenance of lesions at relapse. Therefore, this study provides additional evidence that BCP-ALL is a genetically dynamic disease with distinct genetic profiles at diagnosis and relapse. Integrative NGS, aCGH and MLPA analysis enables better molecular characterization of the genetic profile in BCP-ALL patients during the evolution from diagnosis to relapse. MDPI 2020-07-04 /pmc/articles/PMC7400270/ /pubmed/32635531 http://dx.doi.org/10.3390/diagnostics10070455 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Forero-Castro, Maribel
Montaño, Adrián
Robledo, Cristina
García de Coca, Alfonso
Fuster, José Luis
de las Heras, Natalia
Queizán, José Antonio
Hernández-Sánchez, María
Corchete-Sánchez, Luis A.
Martín-Izquierdo, Marta
Ribera, Jordi
Ribera, José-María
Benito, Rocío
Hernández-Rivas, Jesús M.
Integrated Genomic Analysis of Chromosomal Alterations and Mutations in B-Cell Acute Lymphoblastic Leukemia Reveals Distinct Genetic Profiles at Relapse
title Integrated Genomic Analysis of Chromosomal Alterations and Mutations in B-Cell Acute Lymphoblastic Leukemia Reveals Distinct Genetic Profiles at Relapse
title_full Integrated Genomic Analysis of Chromosomal Alterations and Mutations in B-Cell Acute Lymphoblastic Leukemia Reveals Distinct Genetic Profiles at Relapse
title_fullStr Integrated Genomic Analysis of Chromosomal Alterations and Mutations in B-Cell Acute Lymphoblastic Leukemia Reveals Distinct Genetic Profiles at Relapse
title_full_unstemmed Integrated Genomic Analysis of Chromosomal Alterations and Mutations in B-Cell Acute Lymphoblastic Leukemia Reveals Distinct Genetic Profiles at Relapse
title_short Integrated Genomic Analysis of Chromosomal Alterations and Mutations in B-Cell Acute Lymphoblastic Leukemia Reveals Distinct Genetic Profiles at Relapse
title_sort integrated genomic analysis of chromosomal alterations and mutations in b-cell acute lymphoblastic leukemia reveals distinct genetic profiles at relapse
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7400270/
https://www.ncbi.nlm.nih.gov/pubmed/32635531
http://dx.doi.org/10.3390/diagnostics10070455
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