118P - Molecular diagnostics of gastrointestinal stromal tumors in the era of precision oncology

Background

Gastrointestinal stromal tumors (GISTs) form the most common mesenchymal tumor of the gastrointestinal tract. The majority of GISTs are characterized by activating mutations in the KIT and PDGFRA genes (80 – 85 %). Approximately 10 – 15 % of adult (and 85 % pediatric) GISTs do not have detectable mutations in KIT or PDGFRA genes (KIT/PDGFRA non-mutated GISTs). KIT/PDGFRA non-mutated GISTs are a very heterogeneous group of tumors with alteration in SDH (SDH-deficient GIST accounting for approximately 20–40% of all KIT/PDGFRA no-mutated GISTs), BRAF, NF1, KRAS genes or FGFR1::TACC1, ETV6::NTRK3 fusions.

Methods

We examine the patient's DNA and RNA using Sanger sequencing, High-Resolution Melting, Allele-Specific PCR, and NGS methods to identify mutations of selected genes.

Results

We detected primary mutations in KIT and PDGFRA genes in 84 % of samples (337 samples). The presence of secondary mutations we demonstrated in 17 patients (157 analyzed patients, 11 %) with the progression of the disease. We confirmed significant intratumor and also intertumor heterogeneity of secondary mutations. In the group of KIT/PDGFRA non-mutated GISTs (56 samples), we identify defects in the SDH complex subunits (12 samples, 21 %), mutations in the BRAF (2 samples, 3.5 %) and NF1 (1 sample, 2 %) genes, and alterations in the AKT1 (1 sample, 2 %) and ATR (1 sample, 2 %) genes.

Conclusions

Determination of the GISTsmolecular subtype is very important considering therapeutic decisions in both the adjuvant and metastatic setting. The recent search for therapeutic variants is a significant molecular-genetic contribution to the framework of personalized medicine.

Editorial acknowledgement

The study was supported by Ministry of Health, Czech Republic – conceptual development of research organization, University Hospital Motol, Prague, Czech Republic 00064203.

The funders had no role in the preparation of data, no relationship to the study.

Clinical trial identification

Legal entity responsible for the study

A. Kalfusova.

Funding

The study was supported by Ministry of Health, Czech Republic – conceptual development of research organization, University Hospital Motol, Prague, Czech Republic 00064203. The funders had no role in the preparation of data, no relationship to the study.

Disclosure

All authors have declared no conflicts of interest.