Abstract
Background
Gastrointestinal stromal tumours (GISTs) are prevalent mesenchymal tumours of the gastrointestinal tract, commonly exhibiting structural variations in
KIT
and
PDGFRA
genes. While the mutational profiling of somatic tumours is well described, the genes behind the susceptibility to develop GIST are not yet fully discovered. This study explores the genomic landscape of two primary GIST cases, aiming to identify shared germline pathogenic variants and shed light on potential key players in tumourigenesis.
Methods
Two patients with distinct genotypically and phenotypically GISTs underwent germline whole genome sequencing. CNV and single nucleotide variant (SNV) analyses were performed.
Results
Both patients harbouring low-risk GISTs with different mutations (
PDGFRA
and
KIT
) shared homozygous germline pathogenic deletions in both
CFHR1
and
CFHR3
genes. CNV analysis revealed additional shared pathogenic deletions in other genes such as
SLC25A24
. No particular pathogenic SNV shared by both patients was detected.
Conclusion
Our study provides new insights into germline variants that can be associated with the development of GISTs, namely,
CFHR1
and
CFHR3
deep deletions. Further functional validation is warranted to elucidate the precise contributions of identified germline mutations in GIST development.