Title:Coding and Non-coding: Molecular Portrait of GIST and its Clinical Implication
Volume: 18
Issue: 4
Author(s): I. Bure*, F. Haller and D.V. Zaletaev
Affiliation:
- Medical Genetics Laboratory, Institute of Molecular Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow,Russian Federation
Keywords:
Gastrointestinal stromal tumour, non-coding RNA, oncogenic mutations, miRNA, lncRNA, imatinib
resistance.
Abstract: Gastrointestinal stromal tumours are the most common mesenchymal
tumours of the gastrointestinal tract. Despite similar mutation pattern of activating
mutations in KIT or PDGFRA receptors in 85% of cases, they demonstrate significantly
heterogeneous clinical behaviour and pathological characteristics. This heterogeneity
opens the question of the role of other factors and mechanisms of regulation in the
development of GIST. Additional mutations in downstream effectors of GIST related
signalling pathways or aberrant expression of non-coding RNAs may be additional
contributing factors, the latter being increasingly recognized in carcinogenesis in
general. Recently, a substantial progress has been achieved in understanding the
functional roles of lncRNAs in GIST suggesting their potential employment as
biomarkers and therapeutic targets in GIST. Moreover, some miRNAs have recently
been found to be able to sensitize cells to imatinib, which could be an attractive option to
overcome the resistance to the drug, which hampers the efficacy of GIST treatment.
Therefore, the advantage can be taken of both coding and non-coding parts of the
genome in order to significantly improve prognostication and help find personalized
therapy for patients, depending on a subtype of GIST and personal characteristics.
