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

Author:

Hortal Alejandro1ORCID,Lacuna Marta1,Cifuentes Claudia1ORCID,Alcoceba Miguel23ORCID,Bustelo Xosé R.3ORCID,González Marcos23,Alarcón Balbino1

Affiliation:

1. Immune System Development and Function Program, Centro Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas (CSIC)-Universidad Autónoma de Madrid, 28049 Madrid, Spain

2. Departamento de Hematología, Hospital Universitario de Salamanca (HUS-IBSAL), 37007 Salamanca, Spain

3. Centro de Investigación del Cáncer, Instituto de Biología Molecular y Celular del Cáncer, Centro de Investigación Biomédica en Red de Cáncer, Centro Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas (CSIC), Universidad de Salamanca, 37007 Salamanca, Spain

Abstract

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.

Funder

Spanish Association against Cancer

Publisher

MDPI AG

Subject

Cancer Research,Oncology

Reference24 articles.

1. Chronic Lymphocytic Leukaemia: From Genetics to Treatment;Bosch;Nat. Rev. Clin. Oncol.,2019

2. Cancer Statistics, 2017;Siegel;CA. Cancer J. Clin.,2017

3. Chronic Lymphocytic Leukaemia: ESMO Clinical Practice Guidelines for Diagnosis, Treatment and Follow-Up;Eichhorst;Ann. Oncol.,2021

4. Chronic Lymphocytic Leukaemia;Hallek;Lancet,2018

5. (2022, September 16). Chronic Lymphocytic Leukemia–Cancer Stat Facts, Available online: https://seer.cancer.gov/statfacts/html/clyl.html.

Cited by 2 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3