An Optimized Single Nucleotide Polymorphism-Based Detection Method Suggests That Allelic Variants in the 3’ Untranslated Region of RRAS2 Correlate with Treatment Response in Chronic Lymphocytic Leukemia Patients

Unlike classical RAS genes, oncogenic mutations on RRAS2 are seldomly found in human cancer. By contrast, RRAS2 is frequently found overexpressed in a number of human tumors, including B and T cell lymphomas, breast, gastric, head and neck cancers. In this regard, we have recently shown that overexp...

ver descrição completa

Detalhes bibliográficos
Autores: Hortal, Alejandro, Lacuna, Marta, Cifuentes, Claudia, Alcoceba, Miguel, Bustelo, Xosé R., González, Marcos, Alarcón, Balbino
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/337321
Acesso em linha:http://hdl.handle.net/10261/337321
Access Level:acceso abierto
Palavra-chave:RRAS2
RAS
GTPases
SNP
Polymerase chain reaction
PCR
Chronic lymphocytic leukemia
CLL
Cancer progression
Cancer prognosis
Ibrutinib
Bruton kinase
Cancer treatment
id ES_a8a4bcecb12b19331caa72bb0b8c03c3
oai_identifier_str oai:digital.csic.es:10261/337321
network_acronym_str ES
network_name_str España
repository_id_str
spelling An Optimized Single Nucleotide Polymorphism-Based Detection Method Suggests That Allelic Variants in the 3’ Untranslated Region of RRAS2 Correlate with Treatment Response in Chronic Lymphocytic Leukemia PatientsHortal, AlejandroLacuna, MartaCifuentes, ClaudiaAlcoceba, MiguelBustelo, Xosé R.González, MarcosAlarcón, BalbinoRRAS2RASGTPasesSNPPolymerase chain reactionPCRChronic lymphocytic leukemiaCLLCancer progressionCancer prognosisIbrutinibBruton kinaseCancer treatmentUnlike classical RAS genes, oncogenic mutations on RRAS2 are seldomly found in human cancer. By contrast, RRAS2 is frequently found overexpressed in a number of human tumors, including B and T cell lymphomas, breast, gastric, head and neck cancers. In this regard, we have recently shown that overexpression of wild-type RRAS2 drives the formation of both chronic lymphocytic leukemia (CLL) and breast cancer in mice. In support for the relevance of overexpression of wild type RRAS2 in human cancer, we have found that RRAS2 expression is influenced by the presence of a specific single nucleotide polymorphism (SNP) located in the 3’-untranslated region (UTR) of the RRAS2 mRNA. Perhaps more importantly, the presence of the alternate C, rather than the G allele, at the RRAS2 SNP designated as rs8570 is also associated with worse patient prognosis in CLL. This indicates that the detection of this SNP allelic variants can be informative to predict RRAS2 expression levels and disease long-term evolution in patients. Here, we describe a polymerase chain reaction (PCR)-based method that facilitates the rapid and easy determination of G and C allelic variants of the SNP. Using this approach, we confirm that the C allelic variant is associated with higher expression levels of RRAS2 transcripts and poor patient prognosis. However, we have also found that expression of the C allelic variants correlates with better response to ibrutinib, a Bruton kinase inhibitor commonly used in CLL treatments. This suggests that this method for detecting the RRAS2 rs8570 SNP might be a useful as a tool to predict both patient prognosis and response to targeted therapy in CLL.This study has been supported in part by the Spanish Association against Cancer called “Fundación Científica Asociación Española Contra el Cáncer”, grant number GC16173472GARC.Multidisciplinary Digital Publishing InstituteFundación Científica Asociación Española Contra el CáncerConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2023202320232023info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/337321reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)InglésThe underlying dataset has been published as supplementary material of the article in the publisher platform at 10.3390/cancers15030644http://dx.doi.org/10.3390/cancers15030644Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3373212026-05-22T06:33:51Z
dc.title.none.fl_str_mv An Optimized Single Nucleotide Polymorphism-Based Detection Method Suggests That Allelic Variants in the 3’ Untranslated Region of RRAS2 Correlate with Treatment Response in Chronic Lymphocytic Leukemia Patients
title An Optimized Single Nucleotide Polymorphism-Based Detection Method Suggests That Allelic Variants in the 3’ Untranslated Region of RRAS2 Correlate with Treatment Response in Chronic Lymphocytic Leukemia Patients
spellingShingle An Optimized Single Nucleotide Polymorphism-Based Detection Method Suggests That Allelic Variants in the 3’ Untranslated Region of RRAS2 Correlate with Treatment Response in Chronic Lymphocytic Leukemia Patients
Hortal, Alejandro
RRAS2
RAS
GTPases
SNP
Polymerase chain reaction
PCR
Chronic lymphocytic leukemia
CLL
Cancer progression
Cancer prognosis
Ibrutinib
Bruton kinase
Cancer treatment
title_short An Optimized Single Nucleotide Polymorphism-Based Detection Method Suggests That Allelic Variants in the 3’ Untranslated Region of RRAS2 Correlate with Treatment Response in Chronic Lymphocytic Leukemia Patients
title_full An Optimized Single Nucleotide Polymorphism-Based Detection Method Suggests That Allelic Variants in the 3’ Untranslated Region of RRAS2 Correlate with Treatment Response in Chronic Lymphocytic Leukemia Patients
title_fullStr An Optimized Single Nucleotide Polymorphism-Based Detection Method Suggests That Allelic Variants in the 3’ Untranslated Region of RRAS2 Correlate with Treatment Response in Chronic Lymphocytic Leukemia Patients
title_full_unstemmed An Optimized Single Nucleotide Polymorphism-Based Detection Method Suggests That Allelic Variants in the 3’ Untranslated Region of RRAS2 Correlate with Treatment Response in Chronic Lymphocytic Leukemia Patients
title_sort An Optimized Single Nucleotide Polymorphism-Based Detection Method Suggests That Allelic Variants in the 3’ Untranslated Region of RRAS2 Correlate with Treatment Response in Chronic Lymphocytic Leukemia Patients
dc.creator.none.fl_str_mv Hortal, Alejandro
Lacuna, Marta
Cifuentes, Claudia
Alcoceba, Miguel
Bustelo, Xosé R.
González, Marcos
Alarcón, Balbino
author Hortal, Alejandro
author_facet Hortal, Alejandro
Lacuna, Marta
Cifuentes, Claudia
Alcoceba, Miguel
Bustelo, Xosé R.
González, Marcos
Alarcón, Balbino
author_role author
author2 Lacuna, Marta
Cifuentes, Claudia
Alcoceba, Miguel
Bustelo, Xosé R.
González, Marcos
Alarcón, Balbino
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Fundación Científica Asociación Española Contra el Cáncer
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv RRAS2
RAS
GTPases
SNP
Polymerase chain reaction
PCR
Chronic lymphocytic leukemia
CLL
Cancer progression
Cancer prognosis
Ibrutinib
Bruton kinase
Cancer treatment
topic RRAS2
RAS
GTPases
SNP
Polymerase chain reaction
PCR
Chronic lymphocytic leukemia
CLL
Cancer progression
Cancer prognosis
Ibrutinib
Bruton kinase
Cancer treatment
description Unlike classical RAS genes, oncogenic mutations on RRAS2 are seldomly found in human cancer. By contrast, RRAS2 is frequently found overexpressed in a number of human tumors, including B and T cell lymphomas, breast, gastric, head and neck cancers. In this regard, we have recently shown that overexpression of wild-type RRAS2 drives the formation of both chronic lymphocytic leukemia (CLL) and breast cancer in mice. In support for the relevance of overexpression of wild type RRAS2 in human cancer, we have found that RRAS2 expression is influenced by the presence of a specific single nucleotide polymorphism (SNP) located in the 3’-untranslated region (UTR) of the RRAS2 mRNA. Perhaps more importantly, the presence of the alternate C, rather than the G allele, at the RRAS2 SNP designated as rs8570 is also associated with worse patient prognosis in CLL. This indicates that the detection of this SNP allelic variants can be informative to predict RRAS2 expression levels and disease long-term evolution in patients. Here, we describe a polymerase chain reaction (PCR)-based method that facilitates the rapid and easy determination of G and C allelic variants of the SNP. Using this approach, we confirm that the C allelic variant is associated with higher expression levels of RRAS2 transcripts and poor patient prognosis. However, we have also found that expression of the C allelic variants correlates with better response to ibrutinib, a Bruton kinase inhibitor commonly used in CLL treatments. This suggests that this method for detecting the RRAS2 rs8570 SNP might be a useful as a tool to predict both patient prognosis and response to targeted therapy in CLL.
publishDate 2023
dc.date.none.fl_str_mv 2023
2023
2023
2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/337321
url http://hdl.handle.net/10261/337321
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv The underlying dataset has been published as supplementary material of the article in the publisher platform at 10.3390/cancers15030644
http://dx.doi.org/10.3390/cancers15030644
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869415915658936320
score 15,81155

Registos relacionados