Novel association of CHEK2 mutation in gastrointestinal stromal tumor: A case report and literature review
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract, typically driven by mutations inc-KITorPDGFRA. TheCHEK2gene encodes a checkpoint kinase involved in DNA damage response and has been implicated in hereditary cancer syndromes. However, its r...
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| Veröffentlicht in: | Human Pathology Reports Jg. 42; S. 300794 |
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| Abstract | Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract, typically driven by mutations inc-KITorPDGFRA. TheCHEK2gene encodes a checkpoint kinase involved in DNA damage response and has been implicated in hereditary cancer syndromes. However, its role in GIST pathogenesis remains unexplored.We report the case of a 67-year-old male with recurrent GIST who was found to harbor aCHEK2mutation. The patient initially presented with an abdominal mass, and histopathologic evaluation confirmed a spindle cell neoplasm with strong immunoreactivity for CD117, DOG1, and CD34. Molecular analysis identified a pathogenicCHEK2mutation, a finding not previously described in GIST. The patient was managed with surgical resection following imatinib therapy, with ongoing surveillance for recurrence.The discovery of aCHEK2mutation in GIST raises important questions about its potential role in tumorigenesis and therapeutic response. Given the established involvement ofCHEK2in genomic stability and checkpoint regulation, its presence in GIST warrants further investigation. This case highlights the need to exploreCHEK2mutations in larger cohorts to determine their clinical significance and potential impact on treatment strategies. This case represents the first reported association ofCHEK2mutation with GIST, expanding the known genetic landscape of this tumor. Further studies are necessary to elucidate the implications of this mutation in GIST pathophysiology and treatment. |
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| AbstractList | Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract, typically driven by mutations inc-KITorPDGFRA. TheCHEK2gene encodes a checkpoint kinase involved in DNA damage response and has been implicated in hereditary cancer syndromes. However, its role in GIST pathogenesis remains unexplored.We report the case of a 67-year-old male with recurrent GIST who was found to harbor aCHEK2mutation. The patient initially presented with an abdominal mass, and histopathologic evaluation confirmed a spindle cell neoplasm with strong immunoreactivity for CD117, DOG1, and CD34. Molecular analysis identified a pathogenicCHEK2mutation, a finding not previously described in GIST. The patient was managed with surgical resection following imatinib therapy, with ongoing surveillance for recurrence.The discovery of aCHEK2mutation in GIST raises important questions about its potential role in tumorigenesis and therapeutic response. Given the established involvement ofCHEK2in genomic stability and checkpoint regulation, its presence in GIST warrants further investigation. This case highlights the need to exploreCHEK2mutations in larger cohorts to determine their clinical significance and potential impact on treatment strategies. This case represents the first reported association ofCHEK2mutation with GIST, expanding the known genetic landscape of this tumor. Further studies are necessary to elucidate the implications of this mutation in GIST pathophysiology and treatment. AbstractGastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract, typically driven by mutations in c-KITor PDGFRA. The CHEK2gene encodes a checkpoint kinase involved in DNA damage response and has been implicated in hereditary cancer syndromes. However, its role in GIST pathogenesis remains unexplored. We report the case of a 67-year-old male with recurrent GIST who was found to harbor a CHEK2mutation. The patient initially presented with an abdominal mass, and histopathologic evaluation confirmed a spindle cell neoplasm with strong immunoreactivity for CD117, DOG1, and CD34. Molecular analysis identified a pathogenic CHEK2mutation, a finding not previously described in GIST. The patient was managed with surgical resection following imatinib therapy, with ongoing surveillance for recurrence. The discovery of a CHEK2mutation in GIST raises important questions about its potential role in tumorigenesis and therapeutic response. Given the established involvement of CHEK2in genomic stability and checkpoint regulation, its presence in GIST warrants further investigation. This case highlights the need to explore CHEK2mutations in larger cohorts to determine their clinical significance and potential impact on treatment strategies. This case represents the first reported association of CHEK2mutation with GIST, expanding the known genetic landscape of this tumor. Further studies are necessary to elucidate the implications of this mutation in GIST pathophysiology and treatment. Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract, typically driven by mutations in c-KIT or PDGFRA. The CHEK2 gene encodes a checkpoint kinase involved in DNA damage response and has been implicated in hereditary cancer syndromes. However, its role in GIST pathogenesis remains unexplored. We report the case of a 67-year-old male with recurrent GIST who was found to harbor a CHEK2 mutation. The patient initially presented with an abdominal mass, and histopathologic evaluation confirmed a spindle cell neoplasm with strong immunoreactivity for CD117, DOG1, and CD34. Molecular analysis identified a pathogenic CHEK2 mutation, a finding not previously described in GIST. The patient was managed with surgical resection following imatinib therapy, with ongoing surveillance for recurrence. The discovery of a CHEK2 mutation in GIST raises important questions about its potential role in tumorigenesis and therapeutic response. Given the established involvement of CHEK2 in genomic stability and checkpoint regulation, its presence in GIST warrants further investigation. This case highlights the need to explore CHEK2 mutations in larger cohorts to determine their clinical significance and potential impact on treatment strategies. This case represents the first reported association of CHEK2 mutation with GIST, expanding the known genetic landscape of this tumor. Further studies are necessary to elucidate the implications of this mutation in GIST pathophysiology and treatment. |
| ArticleNumber | 300794 |
| Author | Hu, Trevor T Richman, Allison M. Henderson, Kathryn Abdulrahim, Ahmed F. Groh, Darren Pazhyattil, Joyce |
| Author_xml | – sequence: 1 givenname: Trevor T surname: Hu fullname: Hu, Trevor T email: trevorhu@creighton.edu organization: Creighton University School of Medicine, Omaha, Nebraska, United States – sequence: 2 givenname: Joyce surname: Pazhyattil fullname: Pazhyattil, Joyce email: joycepazhayattil@creighton.edu organization: Department of Pathology, Creighton University, Omaha, Nebraska, United States – sequence: 3 givenname: Allison M. surname: Richman fullname: Richman, Allison M. email: allierichman@creighton.edu organization: Department of Radiology, Creighton University, Omaha, Nebraska, United States – sequence: 4 givenname: Kathryn surname: Henderson fullname: Henderson, Kathryn email: kathrynhenderson@creighton.edu organization: Department of Pathology, Creighton University, Omaha, Nebraska, United States – sequence: 5 givenname: Darren surname: Groh fullname: Groh, Darren email: darrengroh@creighton.edu organization: Department of Pathology, Creighton University, Omaha, Nebraska, United States – sequence: 6 givenname: Ahmed F. surname: Abdulrahim fullname: Abdulrahim, Ahmed F. email: ahmedabdulrahim@creighton.edu organization: Department of Pathology, Creighton University, Omaha, Nebraska, United States |
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| Cites_doi | 10.1093/annonc/mdl274 10.1016/j.ejcb.2020.151075 10.21037/acr-20-83 10.1086/426403 10.5858/2006-130-1466-GSTROM 10.1093/labmed/lmz009 10.1038/sj.onc.1209877 10.1007/s10549-014-3206-1 10.1158/1078-0432.CCR-0778-03 10.4251/wjgo.v5.i6.102 10.1086/346094 |
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| Keywords | CHEK2 mutation c-KIT DNA damage response Tyrosine kinase inhibitors Gastrointestinal stromal tumor |
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| Snippet | Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract, typically driven by mutations inc-KITorPDGFRA.... AbstractGastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract, typically driven by mutations in c-KITor... Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract, typically driven by mutations in c-KIT or PDGFRA.... |
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| SubjectTerms | c-KIT CHEK2 mutation DNA damage response Gastrointestinal stromal tumor Pathology Tyrosine kinase inhibitors |
| Title | Novel association of CHEK2 mutation in gastrointestinal stromal tumor: A case report and literature review |
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