REVIEW

An update on molecular genetics of gastrointestinal stromal tumours

L Tornillo and L M Terracciano

Institute of Pathology, University of Basel, Basel, Switzerland

Correspondence to:
Correspondence to:
Dr Luigi Tornillo
Institute of Pathology, University of Basel, Schönbeinstrasse 40, CH-4003 Basel, Switzerland; tornillol{at}uhbs.ch

Gastrointestinal stromal tumours (GISTs) are the most common primary mesenchymal tumours of the gastrointestinal tract. Most of them show activating mutations of the genes coding for KIT or platelet-derived growth factor receptor (PDGFR), two receptor tyrosine kinases (RTKs). The RTK inhibitor Imatinib (Gleevec®, Novartis, Switzerland), induces regression of the tumour. The level of response to treatment, together with other clinicopathological parameters is related to the type and site of the activating mutation, thus suggesting that these tumours should be classified according to the molecular context. This is confirmed also by the phenomenon of the resistance to treatment, which arises because of different mechanisms (second mutation, amplification, activation of other RTKs) and can be fought only by specific RTK inhibitors, that are at present under development. RTK activation involves an homogeneous transduction pathway whose components (MAPK, AKT, PI3K, mTOR and RAS) are possible targets of new molecular treatment. A new paradigm of classification integrating the classic pathological criteria with the molecular changes will permit personalised prognosis and treatment.

Abbreviations: GIST, gastrointestinal stromal tumours; ICC, interstitial cells of Cajal; PDGFR, Platelet-derived growth factor receptor; PI3K, phosphatidylinositol-3-kinase; RTK, receptor tyrosine kinases

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