Genomic and clinical characterization of a familial GIST kindred intolerant to imatinib
Abstract Familial gastrointestinal stromal tumors (GIST) are rare. We present a kindred with multiple family members affected with multifocal GIST who underwent whole genome sequencing of the germline and tumor. Affected individuals with GIST harbored a germline variant found within exon 13 of the K...
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Nature Portfolio
2024-03-01
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| Series: | npj Genomic Medicine |
| Online Access: | https://doi.org/10.1038/s41525-024-00405-z |
| _version_ | 1797233400018370560 |
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| author | K. M. Ingley M. Zatzman A. M. Fontebasso W. Lo V. Subasri A. Goldenberg Y. Li S. Davidson N. Kanwar L. Waldman L. Brunga Y. Babichev E. G. Demicco A. Gupta M. Szybowska S. Thipphavong D. Malkin A. Villani A. Shlien R. A. Gladdy R. H. Kim |
| author_facet | K. M. Ingley M. Zatzman A. M. Fontebasso W. Lo V. Subasri A. Goldenberg Y. Li S. Davidson N. Kanwar L. Waldman L. Brunga Y. Babichev E. G. Demicco A. Gupta M. Szybowska S. Thipphavong D. Malkin A. Villani A. Shlien R. A. Gladdy R. H. Kim |
| author_sort | K. M. Ingley |
| collection | DOAJ |
| description | Abstract Familial gastrointestinal stromal tumors (GIST) are rare. We present a kindred with multiple family members affected with multifocal GIST who underwent whole genome sequencing of the germline and tumor. Affected individuals with GIST harbored a germline variant found within exon 13 of the KIT gene (c.1965T>G; p.Asn655Lys, p.N655K) and a variant in the MSR1 gene (c.877 C > T; p.Arg293*, pR293X). Multifocal GISTs in the proband and her mother were treated with preoperative imatinib, which resulted in severe intolerance. The clinical features of multifocal GIST, cutaneous mastocytosis, allergies, and gut motility disorders seen in the affected individuals may represent manifestations of the multifunctional roles of KIT in interstitial cells of Cajal or mast cells and/or may be suggestive of additional molecular pathways which can contribute to tumorigenesis. |
| first_indexed | 2024-04-24T16:15:34Z |
| format | Article |
| id | doaj.art-7edfc5a77ead4ecca1d15f59767646b0 |
| institution | Directory Open Access Journal |
| issn | 2056-7944 |
| language | English |
| last_indexed | 2024-04-24T16:15:34Z |
| publishDate | 2024-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Genomic Medicine |
| spelling | doaj.art-7edfc5a77ead4ecca1d15f59767646b02024-03-31T11:27:36ZengNature Portfolionpj Genomic Medicine2056-79442024-03-01911810.1038/s41525-024-00405-zGenomic and clinical characterization of a familial GIST kindred intolerant to imatinibK. M. Ingley0M. Zatzman1A. M. Fontebasso2W. Lo3V. Subasri4A. Goldenberg5Y. Li6S. Davidson7N. Kanwar8L. Waldman9L. Brunga10Y. Babichev11E. G. Demicco12A. Gupta13M. Szybowska14S. Thipphavong15D. Malkin16A. Villani17A. Shlien18R. A. Gladdy19R. H. Kim20Division of Medical Oncology and Hematology, Princess Margaret Cancer CentreDepartment of Laboratory Medicine and Pathobiology, University of TorontoDivision of General Surgery, Sinai Health System, Department of Surgery, University of TorontoDepartment of Laboratory Medicine and Pathobiology, University of TorontoGenetics and Genome Biology Program, The Hospital for Sick ChildrenGenetics and Genome Biology Program, The Hospital for Sick ChildrenDepartment of Pediatric and Laboratory Medicine, The Hospital for Sick ChildrenGenetics and Genome Biology Program, The Hospital for Sick ChildrenDepartment of Pediatric and Laboratory Medicine, The Hospital for Sick ChildrenGenetics and Genome Biology Program, The Hospital for Sick ChildrenGenetics and Genome Biology Program, The Hospital for Sick ChildrenDivision of General Surgery, Sinai Health System, Department of Surgery, University of TorontoDepartment of Pathology and Laboratory Medicine, Sinai Health System, University of TorontoDivision of Medical Oncology and Hematology, Princess Margaret Cancer CentreDivision of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Fred A. Litwin Centre in Genetic Medicine, University Health NetworkDepartment of Radiology, Sinai Health System, University of TorontoDepartment of Pediatrics, Division of Haematology/ Oncology, The Hospital for Sick ChildrenDepartment of Pediatrics, Division of Haematology/ Oncology, The Hospital for Sick ChildrenGenetics and Genome Biology Program, The Hospital for Sick ChildrenDivision of General Surgery, Sinai Health System, Department of Surgery, University of TorontoDivision of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Fred A. Litwin Centre in Genetic Medicine, University Health NetworkAbstract Familial gastrointestinal stromal tumors (GIST) are rare. We present a kindred with multiple family members affected with multifocal GIST who underwent whole genome sequencing of the germline and tumor. Affected individuals with GIST harbored a germline variant found within exon 13 of the KIT gene (c.1965T>G; p.Asn655Lys, p.N655K) and a variant in the MSR1 gene (c.877 C > T; p.Arg293*, pR293X). Multifocal GISTs in the proband and her mother were treated with preoperative imatinib, which resulted in severe intolerance. The clinical features of multifocal GIST, cutaneous mastocytosis, allergies, and gut motility disorders seen in the affected individuals may represent manifestations of the multifunctional roles of KIT in interstitial cells of Cajal or mast cells and/or may be suggestive of additional molecular pathways which can contribute to tumorigenesis.https://doi.org/10.1038/s41525-024-00405-z |
| spellingShingle | K. M. Ingley M. Zatzman A. M. Fontebasso W. Lo V. Subasri A. Goldenberg Y. Li S. Davidson N. Kanwar L. Waldman L. Brunga Y. Babichev E. G. Demicco A. Gupta M. Szybowska S. Thipphavong D. Malkin A. Villani A. Shlien R. A. Gladdy R. H. Kim Genomic and clinical characterization of a familial GIST kindred intolerant to imatinib npj Genomic Medicine |
| title | Genomic and clinical characterization of a familial GIST kindred intolerant to imatinib |
| title_full | Genomic and clinical characterization of a familial GIST kindred intolerant to imatinib |
| title_fullStr | Genomic and clinical characterization of a familial GIST kindred intolerant to imatinib |
| title_full_unstemmed | Genomic and clinical characterization of a familial GIST kindred intolerant to imatinib |
| title_short | Genomic and clinical characterization of a familial GIST kindred intolerant to imatinib |
| title_sort | genomic and clinical characterization of a familial gist kindred intolerant to imatinib |
| url | https://doi.org/10.1038/s41525-024-00405-z |
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