@article {812, title = {Shared germline genomic variants in two patients with double primary gastrointestinal stromal tumours (GISTs).}, journal = {J Med Genet}, volume = {61}, year = {2024}, month = {2024 Sep 24}, pages = {927-934}, abstract = {

BACKGROUND: Gastrointestinal stromal tumours (GISTs) are prevalent mesenchymal tumours of the gastrointestinal tract, commonly exhibiting structural variations in and 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 ( and ) shared homozygous germline pathogenic deletions in both and genes. CNV analysis revealed additional shared pathogenic deletions in other genes such as . 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, and deep deletions. Further functional validation is warranted to elucidate the precise contributions of identified germline mutations in GIST development.

}, keywords = {DNA Copy Number Variations, Female, Gastrointestinal Neoplasms, Gastrointestinal Stromal Tumors, Genetic Predisposition to Disease, Germ-Line Mutation, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Proto-Oncogene Proteins c-kit, Receptor, Platelet-Derived Growth Factor alpha, Whole Genome Sequencing}, issn = {1468-6244}, doi = {10.1136/jmg-2024-110109}, author = {Moura, David S and L{\'o}pez L{\'o}pez, Daniel and di Lernia, Davide and Martin-Ruiz, Marta and Lopez-Alvarez, Maria and Ramos, Rafael and Merino, Jose and Dopazo, Joaquin and Lopez-Guerrero, Jose and Mondaza-Hernandez, Jose L and Romero, Pablo and Hindi, Nadia and Garcia-Foncillas, Jesus and Martin-Broto, Javier} }