Integrated Genomic Analysis of Chromosomal Alterations and Mutations in B-Cell Acute Lymphoblastic Leukemia Reveals Distinct Genetic Profiles at Relapse
Forero-Castro, Maribel (Universidad Pedagógica y Tecnológica de Colombia)
Montaño, Adrián (Universidad de Salamanca)
Robledo, Cristina (Universidad de Salamanca)
García de Coca, Alfonso (Hospital Clínico Universitario de Valladolid)
Fuster, José Luis (Hospital Universitario Virgen de la Arrixaca (Múrcia))
De las Heras, Natalia (Hospital Virgen Blanca (León))
Queizán, José Antonio (Hospital General de Segovia)
Hernández-Sánchez, María (Universidad de Salamanca)
Corchete Sánchez, Luis Antonio (Hospital Universitario de Salamanca)
Martín-Izquierdo, Marta (Universidad de Salamanca)
Ribera Salas, Jordi (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Ribera, Jose-Maria (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Benito, Rocío (Universidad de Salamanca)
Hernández Rivas, Jesús María (Hospital Universitario de Salamanca)

Date:	2020
Abstract:	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.
Grants:	Instituto de Salud Carlos III AC18-00093 Instituto de Salud Carlos III PI14-01971 Instituto de Salud Carlos III CD19-0022
Note:	Altres ajuts: FSE/JCYL-EDU/556/2019
Note:	Altres ajuts: FEDER/SA085U16
Note:	Altres ajuts: FEDER/SA271P18
Note:	Altres ajuts: FEDER/CIBERONC/CB16-12-0023
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Acute lymphoblastic leukemia (ALL) ; Relapse ; Next-generation sequencing (NGS) ; Array comparative genomic hybridization (aCGH) ; Multiplex ligation-dependent probe amplification (MLPA) ; IKZF1 ; TP53
Published in:	Diagnostics, Vol. 10 (july 2020) , ISSN 2075-4418

DOI: 10.3390/diagnostics10070455
PMID: 32635531

13 p, 1.8 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Josep Carreras Leukaemia Research Institute
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Articles > Published articles