A Review of Genomic Testing and SDH‐ Deficiency in Gastrointestinal Stromal Tumors: Getting to the GIST
ABSTRACT Gastrointestinal Stromal Tumors (GISTs) have seen significant advancements in their diagnosis and management, driven by targeted therapeutic development and molecular testing. The identification of mutations in genes such as KIT and PDGFRA has transformed treatment approaches, particularly...
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| Format: | Article |
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Wiley
2025-02-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.70669 |
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| author | Vaia Florou Michelle F. Jacobs Ruth Casey Denisse Evans Becky Owens Margarita Raygada Sara Rothschild Samantha E. Greenberg |
| author_facet | Vaia Florou Michelle F. Jacobs Ruth Casey Denisse Evans Becky Owens Margarita Raygada Sara Rothschild Samantha E. Greenberg |
| author_sort | Vaia Florou |
| collection | DOAJ |
| description | ABSTRACT Gastrointestinal Stromal Tumors (GISTs) have seen significant advancements in their diagnosis and management, driven by targeted therapeutic development and molecular testing. The identification of mutations in genes such as KIT and PDGFRA has transformed treatment approaches, particularly through targeted therapies like imatinib, which have improved patient outcomes. This review explores the critical role of genomic testing in GIST, highlighting its importance in accurate diagnosis, treatment planning, and long‐term surveillance for KIT/PDGFRA negative, SDH‐deficient GISTs. SDH‐deficient GISTs arise from mutations or epigenetic changes affecting the succinate dehydrogenase complex. The complexity of SDH‐deficient GISTs, including their association with hereditary syndromes such as Hereditary Paraganglioma‐Pheochromocytoma and/or hypermethylation of the SDHC promoter, underscores the need for comprehensive germline testing. Despite the availability of guidelines, variability exists in genomic testing recommendations across different regions, necessitating a unified approach. This review proposes a simplified algorithm for the genomic workup of GIST, and suggests all individuals with SDH‐deficient GIST, regardless of germline testing result, require monitoring for additional SDHx‐related tumors, given the lack of widely available methylation and full gene SDHA analysis. |
| format | Article |
| id | doaj-art-e77c09fabd364bcda122824304c10744 |
| institution | OA Journals |
| issn | 2045-7634 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj-art-e77c09fabd364bcda122824304c107442025-08-20T02:22:09ZengWileyCancer Medicine2045-76342025-02-01143n/an/a10.1002/cam4.70669A Review of Genomic Testing and SDH‐ Deficiency in Gastrointestinal Stromal Tumors: Getting to the GISTVaia Florou0Michelle F. Jacobs1Ruth Casey2Denisse Evans3Becky Owens4Margarita Raygada5Sara Rothschild6Samantha E. Greenberg7Division of Oncology, Department of Internal Medicine, Huntsman Cancer Institute University of Utah Salt Lake City Utah USADivision of Genetic Medicine, Department of Internal Medicine University of Michigan Ann Arbor Michigan USADepartment of Medical Genetics Cambridge University Cambridge UKLife Raft Group Wayne New Jersey USALife Raft Group Wayne New Jersey USAPediatric Oncology and Neuro‐Oncology Branch National Cancer Institute/National Institutes of Health Bethesda Maryland USALife Raft Group Wayne New Jersey USADepartment of Health Care Sciences UT Southwestern Medical Center Dallas Texas USAABSTRACT Gastrointestinal Stromal Tumors (GISTs) have seen significant advancements in their diagnosis and management, driven by targeted therapeutic development and molecular testing. The identification of mutations in genes such as KIT and PDGFRA has transformed treatment approaches, particularly through targeted therapies like imatinib, which have improved patient outcomes. This review explores the critical role of genomic testing in GIST, highlighting its importance in accurate diagnosis, treatment planning, and long‐term surveillance for KIT/PDGFRA negative, SDH‐deficient GISTs. SDH‐deficient GISTs arise from mutations or epigenetic changes affecting the succinate dehydrogenase complex. The complexity of SDH‐deficient GISTs, including their association with hereditary syndromes such as Hereditary Paraganglioma‐Pheochromocytoma and/or hypermethylation of the SDHC promoter, underscores the need for comprehensive germline testing. Despite the availability of guidelines, variability exists in genomic testing recommendations across different regions, necessitating a unified approach. This review proposes a simplified algorithm for the genomic workup of GIST, and suggests all individuals with SDH‐deficient GIST, regardless of germline testing result, require monitoring for additional SDHx‐related tumors, given the lack of widely available methylation and full gene SDHA analysis.https://doi.org/10.1002/cam4.70669gastrointestinal stromal tumor (GIST)genomic testinghereditary paraganglioma‐pheochromocytomaSDH‐deficient GISTsuccinate dehydrogenase complex |
| spellingShingle | Vaia Florou Michelle F. Jacobs Ruth Casey Denisse Evans Becky Owens Margarita Raygada Sara Rothschild Samantha E. Greenberg A Review of Genomic Testing and SDH‐ Deficiency in Gastrointestinal Stromal Tumors: Getting to the GIST Cancer Medicine gastrointestinal stromal tumor (GIST) genomic testing hereditary paraganglioma‐pheochromocytoma SDH‐deficient GIST succinate dehydrogenase complex |
| title | A Review of Genomic Testing and SDH‐ Deficiency in Gastrointestinal Stromal Tumors: Getting to the GIST |
| title_full | A Review of Genomic Testing and SDH‐ Deficiency in Gastrointestinal Stromal Tumors: Getting to the GIST |
| title_fullStr | A Review of Genomic Testing and SDH‐ Deficiency in Gastrointestinal Stromal Tumors: Getting to the GIST |
| title_full_unstemmed | A Review of Genomic Testing and SDH‐ Deficiency in Gastrointestinal Stromal Tumors: Getting to the GIST |
| title_short | A Review of Genomic Testing and SDH‐ Deficiency in Gastrointestinal Stromal Tumors: Getting to the GIST |
| title_sort | review of genomic testing and sdh deficiency in gastrointestinal stromal tumors getting to the gist |
| topic | gastrointestinal stromal tumor (GIST) genomic testing hereditary paraganglioma‐pheochromocytoma SDH‐deficient GIST succinate dehydrogenase complex |
| url | https://doi.org/10.1002/cam4.70669 |
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