Frequent variations in cancer-related genes may play prognostic role in treatment of patients with chronic myeloid leukemia

BMC Genetics

Research

Elmira P. Adilgereeva¹  Svetlana A. Smirnikhina¹  Alexander V. Lavrov²  Sergey I. Kutsev²  Anna G. Turkina³  Ekaterina Y. Chelysheva³  Oleg A. Shukhov³ 

[1] Laboratory of Mutagenesis, Federal State Budgetary Institution “Research Centre for Medical Genetics”, Moskvorechie, 1, 115478, Moscow, Russia;Laboratory of Mutagenesis, Federal State Budgetary Institution “Research Centre for Medical Genetics”, Moskvorechie, 1, 115478, Moscow, Russia;Department of Molecular and Cellular Genetics, State Budgetary Educational Institution of Higher Professional Education “Russian National Research Medical University named after N.I. Pirogov” of Ministry of Health of the Russian Federation, Moscow, Russia;Scientific and Advisory Department of Chemotherapy of Myeloproliferative Disorders, Federal State-Funded Institution National Research Center for Hematology of the Ministry of Healthcare of the Russian Federation, Moscow, Russia;

关键词: Genetic variation;    Chronic myeloid leukemia;    TKI resistance;    Whole exome sequencing;    Biomarkers;    Prognostic factors;   

DOI  :  10.1186/s12863-015-0308-7

来源: Springer

【 摘 要 】

BackgroundGenome variability of host genome and cancer cells play critical role in diversity of response to existing therapies and overall success in treating oncological diseases. In chronic myeloid leukemia targeted therapy with tyrosine kinase inhibitors demonstrates high efficacy in most of the patients. However about 15 % of patients demonstrate primary resistance to standard therapy. Whole exome sequencing is a good tool for unbiased search of genetic variations important for prognosis of survival and therapy efficacy in many cancers. We apply this approach to CML patients with optimal response and failure of tyrosine kinase therapy.ResultsWe analyzed exome variations between optimal responders and failures and found 7 variants in cancer-related genes with different genotypes in two groups of patients. Five of them were found in optimal responders: rs11579366, rs1990236, rs176037, rs10653661, rs3803264 and two in failures: rs3099950, rs9471966. These variants were found in genes associated with cancers (ANKRD35, DNAH9, MAGEC1, TOX3) or participating in cancer-related signaling pathways (THSD1, MORN2, PTCRA).ConclusionWe found gene variants which may become early predictors of the therapy outcome and allow development of new early prognostic tests for estimation of therapy efficacy in CML patients. Normal genetic variation may influence therapy efficacy during targeted treatment of cancers.

【 授权许可】

CC BY   
© Lavrov et al. 2015