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

Abstract

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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12863-015-0308-7) contains supplementary material, which is available to authorized users.

The complex genetic landscape of familial MDS and AML reveals pathogenic germline variants

“…Among the non-syndromic genes, we noted DNAH9 with variants in three families, a gene that interacts with the hematopoietic regulator BCL6 48 and is also mutated in one of the families described by Churpek et al 40 . In another family we identified a variant in SH2B3 (p.Ala49Thr), implicated in hematopoietic stem cell self-renewal and quiescence through direct interaction with JAK2 [49][50][51] , with the variant adjacent to a frameshift variant described by Bluteau et al 42 (p.Arg50-Glyfs*147) (Fig.…”

Exome, transcriptome and miRNA analysis don’t reveal any molecular markers of TKI efficacy in primary CML patients

“…Direct DNA Sanger sequencing of PCR products was performed as described previously [ 13 ]. Briefly, DNA from peripheral blood samples was obtained from CML patients before TKI therapy.…”

“…A variety of polymorphisms and mutations in genes associated with TKI resistance was reported [ 10 – 12 ]. Recently we have performed whole-exome sequencing in primary CML patients before TKI administration and revealed five genetic variants typical for optimal responders (rs11579366 in ANKRD35 , rs1990236 in DNAH9 , rs176037 in MAGEC1 , rs10653661 in TOX3 , rs3803264 in THSD1 ) and two – for non-optimal responders (rs3099950 in MORN2 , rs9471966 in PTCRA ) [ 13 ].…”

The papers presented at 7th Young Scientists School “Systems Biology and Bioinformatics” (SBB’15): Introductory Note

“…The paper of Lavrov and co-authors titled "Frequent variations in cancer-related genes may play prognostic role in treatment of patients with chronic myeloid leukemia" convincingly demonstrated that the gene variants present or absent in the genome of patient influence relative efficiency of the therapy for chronic myeloid leukemia, thus, paving a way to personalized approach to the treatment of this disease [4].…”