167P - Molecular analysis of gastrointestinal stromal tumor (GIST): The experience of Regina Elena National Cancer Institute

Background

GISTs are rare soft tissue neoplasms harboring, in most cases, activating mutations in KIT and PDGFRA genes. The aim of this study is to describe the molecular characteristics of GIST samples from Regina Elena National Cancer Institute.

Methods

We collected sequencing data from 153 samples from GIST patients between January 2017 and March 2023. Next generation sequencing was performed on samples derived from surgical excision or biopsy of the primary or metastatic lesions. The Ion AmpliSeq Cancer Hotspot panel V2 and the Oncomine Focus Assay (Thermofisher Scientific) were used. The analysis was performed with R-4.2.2 and oncokb-annotator.

Results

The top 5 mutated genes were KIT (69% of the cases), TP53 (63%), PDGFRA (20%), KDR (20%), and PIK3CA (17%); the median number of variants per sample was 3. The most affected exons in KIT were 11 (51%), 9 (13.9%), 10 (13.3%); exon 17 harbored 3.3% of the variants; exon 13 1.3%. The most affected exons in PDGFRA were 18 (36.6%) and 10 (34.1%); the mutations in exons 14 and 12 accounted, respectively, for 7.3% and 4.9% of the cases. We annotated the variants according to OncoKB Therapeutic Levels of Evidence V2: 74 out of 631 total variants (11.7%) were annotated as oncogenic, 86 (13.6%) as likely oncogenic, 14 (2.2%) as likely neutral and 457 (72.4%) as inconclusive or unknown. Among the 160 oncogenic or likely oncogenic variants, 103 (64.4%) had a therapeutic level 1, 18 (11.3%) level 2, 9 (5.6%) level R1, 5 (3.1%) level R2. As for the KIT gene, 90 of the 151 variants (59.6%) were annotated as oncogenic or likely oncogenic, all of them had a therapeutic level 1, 5 (3.3%) had level R2. Regarding the PDGFRA gene, 14 out of 41 variants (34.1%) were annotated as oncogenic or likely oncogenic, all but one had a therapeutic level 1, 14 level 2, 9 level R1. The remaining oncogenic or likely oncogenic variants affected the following genes: KDR (19.4%), TP53 (8.8%), CTNNB1, JAK2, FBXW7, GNAS, NF1, PIK3CA, RB1, RET; 2 of them had a therapeutic level 3B, 1 level 4.

Conclusions

Most of the recorded variants were in KIT and PDGFRA genes. More than half of them are oncogenic and targetable. Notably, we found other oncogenic variants that can have a role in the development of the disease and in the onset of resistance to the treatment.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

B. Casini: Financial Interests, Personal, Other: Novartis, GSK.V. Ferraresi: Financial Interests, Personal, Invited Speaker: Novartis, Pierre Fabre, Bristol Myers Squibb, MSD, PharmaMar. All other authors have declared no conflicts of interest.