Open Access Highly Accessed Research article

Functional features of gene expression profiles differentiating gastrointestinal stromal tumours according to KIT mutations and expression

Jerzy Ostrowski12*, Marcin Polkowski12, Agnieszka Paziewska1, Magdalena Skrzypczak1, Krzysztof Goryca1, Tymon Rubel27, Katarzyna Kokoszyñska78, Piotr Rutkowski3, Zbigniew I Nowecki3, Anna Jerzak Vel Dobosz4, Dorota Jarosz125, Wlodzimierz Ruka3 and Lucjan S Wyrwicz67

Author Affiliations

1 Department of Gastroenterology and Hepatology, Medical Center for Postgraduate Education, Warsaw, Poland

2 Department of Gastroenterology, M Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland

3 Department of Soft Tissue/Bone Sarcoma and Melanoma, M Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland

4 Department of Molecular Biology, M Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland

5 Department of Pathology, M Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland

6 Department of Colorectal Cancer, M Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland

7 Laboratory of Bioinformatics and Systems Biology M Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland

8 Bioinfobank Institute, Poznan, Poland

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BMC Cancer 2009, 9:413  doi:10.1186/1471-2407-9-413

Published: 27 November 2009

Abstract

Background

Gastrointestinal stromal tumours (GISTs) represent a heterogeneous group of tumours of mesenchymal origin characterized by gain-of-function mutations in KIT or PDGFRA of the type III receptor tyrosine kinase family. Although mutations in either receptor are thought to drive an early oncogenic event through similar pathways, two previous studies reported the mutation-specific gene expression profiles. However, their further conclusions were rather discordant. To clarify the molecular characteristics of differentially expressed genes according to GIST receptor mutations, we combined microarray-based analysis with detailed functional annotations.

Methods

Total RNA was isolated from 29 frozen gastric GISTs and processed for hybridization on GENECHIP® HG-U133 Plus 2.0 microarrays (Affymetrix). KIT and PDGFRA were analyzed by sequencing, while related mRNA levels were analyzed by quantitative RT-PCR.

Results

Fifteen and eleven tumours possessed mutations in KIT and PDGFRA, respectively; no mutation was found in three tumours. Gene expression analysis identified no discriminative profiles associated with clinical or pathological parameters, even though expression of hundreds of genes differentiated tumour receptor mutation and expression status. Functional features of genes differentially expressed between the two groups of GISTs suggested alterations in angiogenesis and G-protein-related and calcium signalling.

Conclusion

Our study has identified novel molecular elements likely to be involved in receptor-dependent GIST development and allowed confirmation of previously published results. These elements may be potential therapeutic targets and novel markers of KIT mutation status.