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Loss of Heterozygosity in the Tumor DNA of De Novo Diagnosed Patients Is Associated with Poor Outcome for B-ALL but Not for T-ALL

Despite the introduction of new technologies in molecular diagnostics, one should not underestimate the traditional routine methods for studying tumor DNA. Here we present the evidence that short tandem repeat (STR) profiling of tumor DNA relative to DNA from healthy cells might identify chromosomal...

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Autores principales: Risinskaya, Natalya, Kozhevnikova, Yana, Gavrilina, Olga, Chabaeva, Julia, Kotova, Ekaterina, Yushkova, Anna, Isinova, Galina, Zarubina, Ksenija, Obukhova, Tatiana, Kulikov, Sergey, Julhakyan, Hunan, Sudarikov, Andrey, Parovichnikova, Elena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8952291/
https://www.ncbi.nlm.nih.gov/pubmed/35327952
http://dx.doi.org/10.3390/genes13030398
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author Risinskaya, Natalya
Kozhevnikova, Yana
Gavrilina, Olga
Chabaeva, Julia
Kotova, Ekaterina
Yushkova, Anna
Isinova, Galina
Zarubina, Ksenija
Obukhova, Tatiana
Kulikov, Sergey
Julhakyan, Hunan
Sudarikov, Andrey
Parovichnikova, Elena
author_facet Risinskaya, Natalya
Kozhevnikova, Yana
Gavrilina, Olga
Chabaeva, Julia
Kotova, Ekaterina
Yushkova, Anna
Isinova, Galina
Zarubina, Ksenija
Obukhova, Tatiana
Kulikov, Sergey
Julhakyan, Hunan
Sudarikov, Andrey
Parovichnikova, Elena
author_sort Risinskaya, Natalya
collection PubMed
description Despite the introduction of new technologies in molecular diagnostics, one should not underestimate the traditional routine methods for studying tumor DNA. Here we present the evidence that short tandem repeat (STR) profiling of tumor DNA relative to DNA from healthy cells might identify chromosomal aberrations affecting therapy outcome. Tumor STR profiles of 87 adult patients with de novo Ph-negative ALL (40 B-ALL, 43 T-ALL, 4 mixed phenotype acute leukemia (MPAL)) treated according to the “RALL-2016” regimen were analyzed. DNA of tumor cells was isolated from patient bone marrow samples taken at diagnosis. Control DNA samples were taken from the buccal swab or the blood of patients in complete remission. Overall survival (OS) analysis was used to assess the independent impact of the LOH as a risk factor. Of the 87 patients, 21 were found with LOH in various STR loci (24%). For B-ALL patients, LOH (except 12p LOH) was an independent risk factor (OS hazard ratio 3.89, log-rank p-value 0.0395). In contrast, for T-ALL patients, the OS hazard ratio was 0.59 (log-rank p-value 0.62). LOH in particular STR loci measured at the onset of the disease could be used as a prognostic factor for poor outcome in B-ALL, but not in T-ALL.
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spelling pubmed-89522912022-03-26 Loss of Heterozygosity in the Tumor DNA of De Novo Diagnosed Patients Is Associated with Poor Outcome for B-ALL but Not for T-ALL Risinskaya, Natalya Kozhevnikova, Yana Gavrilina, Olga Chabaeva, Julia Kotova, Ekaterina Yushkova, Anna Isinova, Galina Zarubina, Ksenija Obukhova, Tatiana Kulikov, Sergey Julhakyan, Hunan Sudarikov, Andrey Parovichnikova, Elena Genes (Basel) Article Despite the introduction of new technologies in molecular diagnostics, one should not underestimate the traditional routine methods for studying tumor DNA. Here we present the evidence that short tandem repeat (STR) profiling of tumor DNA relative to DNA from healthy cells might identify chromosomal aberrations affecting therapy outcome. Tumor STR profiles of 87 adult patients with de novo Ph-negative ALL (40 B-ALL, 43 T-ALL, 4 mixed phenotype acute leukemia (MPAL)) treated according to the “RALL-2016” regimen were analyzed. DNA of tumor cells was isolated from patient bone marrow samples taken at diagnosis. Control DNA samples were taken from the buccal swab or the blood of patients in complete remission. Overall survival (OS) analysis was used to assess the independent impact of the LOH as a risk factor. Of the 87 patients, 21 were found with LOH in various STR loci (24%). For B-ALL patients, LOH (except 12p LOH) was an independent risk factor (OS hazard ratio 3.89, log-rank p-value 0.0395). In contrast, for T-ALL patients, the OS hazard ratio was 0.59 (log-rank p-value 0.62). LOH in particular STR loci measured at the onset of the disease could be used as a prognostic factor for poor outcome in B-ALL, but not in T-ALL. MDPI 2022-02-23 /pmc/articles/PMC8952291/ /pubmed/35327952 http://dx.doi.org/10.3390/genes13030398 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Risinskaya, Natalya
Kozhevnikova, Yana
Gavrilina, Olga
Chabaeva, Julia
Kotova, Ekaterina
Yushkova, Anna
Isinova, Galina
Zarubina, Ksenija
Obukhova, Tatiana
Kulikov, Sergey
Julhakyan, Hunan
Sudarikov, Andrey
Parovichnikova, Elena
Loss of Heterozygosity in the Tumor DNA of De Novo Diagnosed Patients Is Associated with Poor Outcome for B-ALL but Not for T-ALL
title Loss of Heterozygosity in the Tumor DNA of De Novo Diagnosed Patients Is Associated with Poor Outcome for B-ALL but Not for T-ALL
title_full Loss of Heterozygosity in the Tumor DNA of De Novo Diagnosed Patients Is Associated with Poor Outcome for B-ALL but Not for T-ALL
title_fullStr Loss of Heterozygosity in the Tumor DNA of De Novo Diagnosed Patients Is Associated with Poor Outcome for B-ALL but Not for T-ALL
title_full_unstemmed Loss of Heterozygosity in the Tumor DNA of De Novo Diagnosed Patients Is Associated with Poor Outcome for B-ALL but Not for T-ALL
title_short Loss of Heterozygosity in the Tumor DNA of De Novo Diagnosed Patients Is Associated with Poor Outcome for B-ALL but Not for T-ALL
title_sort loss of heterozygosity in the tumor dna of de novo diagnosed patients is associated with poor outcome for b-all but not for t-all
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8952291/
https://www.ncbi.nlm.nih.gov/pubmed/35327952
http://dx.doi.org/10.3390/genes13030398
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