Molecular Profiling of KIT/PDGFRA-Mutant and Wild-Type Gastrointestinal Stromal Tumors (GISTs) with Clinicopathological Correlation
In gastrointestinal stromal tumors (GISTs), identifying prototypical mutations in the KIT/PDGFRA oncogenes, or in rare alternate genes, is essential for prognostication and predicting response to tyrosine kinase inhibitors. Conversely, wild-type GISTs (WT-GIST), which lack known mutations, have limi...
Saved in:
| Main Author: | |
|---|---|
| Other Authors: | , , , , , , , , , , , |
| Published: |
2024
|
| Online Access: | http://hdl.handle.net/11675/12201 http://www.scopus.com/inward/record.url?scp=85202516640&partnerID=8YFLogxK |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1870679718779420672 |
|---|---|
| author | Ahmed, Amir A. |
| author2 | Alateeqi, Mona Ali, Rola H. Alkandari, Mohammad Almarzooq, Ammar Alnajjar, Abdulsalam Alqallaf, Zainab Alsaber, Ahmad Bahzad, Shakir Benobaid, Noelle Jama, Hiba Mohammed, Eiman M.A. Mohanty, Asit K. |
| author2_role | author author author author author author author author author author author author |
| author_facet | Ahmed, Amir A. Alateeqi, Mona Ali, Rola H. Alkandari, Mohammad Almarzooq, Ammar Alnajjar, Abdulsalam Alqallaf, Zainab Alsaber, Ahmad Bahzad, Shakir Benobaid, Noelle Jama, Hiba Mohammed, Eiman M.A. Mohanty, Asit K. |
| author_role | author |
| dc.creator.none.fl_str_mv | Ahmed, Amir A. Alateeqi, Mona Ali, Rola H. Alkandari, Mohammad Almarzooq, Ammar Alnajjar, Abdulsalam Alqallaf, Zainab Alsaber, Ahmad Bahzad, Shakir Benobaid, Noelle Jama, Hiba Mohammed, Eiman M.A. Mohanty, Asit K. |
| dc.date.none.fl_str_mv | 2024-08-21 2025-03-10T09:16:32Z 2025-03-10T09:16:32Z |
| dc.identifier.none.fl_str_mv | 10.3390/cancers16162907 http://hdl.handle.net/11675/12201 http://www.scopus.com/inward/record.url?scp=85202516640&partnerID=8YFLogxK |
| dc.publisher.none.fl_str_mv | Multidisciplinary Digital Publishing Institute (MDPI) |
| dc.relation.none.fl_str_mv | Department of Management- CBE Cancers |
| dc.title.none.fl_str_mv | Molecular Profiling of KIT/PDGFRA-Mutant and Wild-Type Gastrointestinal Stromal Tumors (GISTs) with Clinicopathological Correlation |
| dc.type.none.fl_str_mv | Journal Article Peer-reviewed info:eu-repo/semantics/publishedVersion |
| description | In gastrointestinal stromal tumors (GISTs), identifying prototypical mutations in the KIT/PDGFRA oncogenes, or in rare alternate genes, is essential for prognostication and predicting response to tyrosine kinase inhibitors. Conversely, wild-type GISTs (WT-GIST), which lack known mutations, have limited treatment options. Data on the mutational landscape of GISTs and their impact on disease progression are very limited in Kuwait. Using a targeted next-generation sequencing panel, we investigated the spectrum and frequency of KIT, PDGFRA, and RAS-pathway-related mutations in 95 out of 200 GISTs diagnosed at Kuwait Cancer Center from 2005 to 2023 and assessed their correlation with clinicopathological parameters. Among the 200 tumors (median age 55 years; 15–91), 54% originated in the stomach, 33% in the small bowel, 7% in the colorectum, 1.5% in the peritoneum, and 4.5% had an unknown primary site. Of the 95 molecularly profiled cases, 88% had a mutation: KIT (61%), PDGFRA (25%), NF1 (2%), and one NTRK1 rearrangement. Ten WT-GISTs were identified (stomach = 6, small bowel = 2, and colorectum = 2). WT-GISTs tended to be smaller (median 4.0 cm; 0.5–8.0) (p = 0.018), with mitosis ?5/5 mm2, and were of lower risk (p = 0.019). KIT mutations were an adverse indicator of disease progression (p = 0.049), while wild-type status did not significantly impact progression (p = 0.934). The genetic landscape in this cohort mirrors that of global studies, but regional collaborations are needed to correlate outcomes with genetic variants. |
| id | AUKR_1cc0cc1cbbad696b0a09865833efbe39 |
| identifier_str_mv | 10.3390/cancers16162907 |
| network_acronym_str | AUKR |
| network_name_str | AU Kuwait Rep |
| oai_identifier_str | oai:dspace.auk.edu.kw:11675/12201 |
| publishDate | 2024 |
| publisher.none.fl_str_mv | Multidisciplinary Digital Publishing Institute (MDPI) |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| spelling | Molecular Profiling of KIT/PDGFRA-Mutant and Wild-Type Gastrointestinal Stromal Tumors (GISTs) with Clinicopathological CorrelationAhmed, Amir A.Alateeqi, MonaAli, Rola H.Alkandari, MohammadAlmarzooq, AmmarAlnajjar, AbdulsalamAlqallaf, ZainabAlsaber, Ahmad Bahzad, ShakirBenobaid, NoelleJama, HibaMohammed, Eiman M.A.Mohanty, Asit K.In gastrointestinal stromal tumors (GISTs), identifying prototypical mutations in the KIT/PDGFRA oncogenes, or in rare alternate genes, is essential for prognostication and predicting response to tyrosine kinase inhibitors. Conversely, wild-type GISTs (WT-GIST), which lack known mutations, have limited treatment options. Data on the mutational landscape of GISTs and their impact on disease progression are very limited in Kuwait. Using a targeted next-generation sequencing panel, we investigated the spectrum and frequency of KIT, PDGFRA, and RAS-pathway-related mutations in 95 out of 200 GISTs diagnosed at Kuwait Cancer Center from 2005 to 2023 and assessed their correlation with clinicopathological parameters. Among the 200 tumors (median age 55 years; 15–91), 54% originated in the stomach, 33% in the small bowel, 7% in the colorectum, 1.5% in the peritoneum, and 4.5% had an unknown primary site. Of the 95 molecularly profiled cases, 88% had a mutation: KIT (61%), PDGFRA (25%), NF1 (2%), and one NTRK1 rearrangement. Ten WT-GISTs were identified (stomach = 6, small bowel = 2, and colorectum = 2). WT-GISTs tended to be smaller (median 4.0 cm; 0.5–8.0) (p = 0.018), with mitosis ?5/5 mm2, and were of lower risk (p = 0.019). KIT mutations were an adverse indicator of disease progression (p = 0.049), while wild-type status did not significantly impact progression (p = 0.934). The genetic landscape in this cohort mirrors that of global studies, but regional collaborations are needed to correlate outcomes with genetic variants.Multidisciplinary Digital Publishing Institute (MDPI)2025-03-10T09:16:32Z2025-03-10T09:16:32Z2024-08-21Journal ArticlePeer-reviewedinfo:eu-repo/semantics/publishedVersion10.3390/cancers16162907http://hdl.handle.net/11675/12201http://www.scopus.com/inward/record.url?scp=85202516640&partnerID=8YFLogxKDepartment of Management- CBECancersoai:dspace.auk.edu.kw:11675/122012025-06-22T10:24:15Z |
| spellingShingle | Molecular Profiling of KIT/PDGFRA-Mutant and Wild-Type Gastrointestinal Stromal Tumors (GISTs) with Clinicopathological Correlation Ahmed, Amir A. |
| status_str | publishedVersion |
| title | Molecular Profiling of KIT/PDGFRA-Mutant and Wild-Type Gastrointestinal Stromal Tumors (GISTs) with Clinicopathological Correlation |
| title_full | Molecular Profiling of KIT/PDGFRA-Mutant and Wild-Type Gastrointestinal Stromal Tumors (GISTs) with Clinicopathological Correlation |
| title_fullStr | Molecular Profiling of KIT/PDGFRA-Mutant and Wild-Type Gastrointestinal Stromal Tumors (GISTs) with Clinicopathological Correlation |
| title_full_unstemmed | Molecular Profiling of KIT/PDGFRA-Mutant and Wild-Type Gastrointestinal Stromal Tumors (GISTs) with Clinicopathological Correlation |
| title_short | Molecular Profiling of KIT/PDGFRA-Mutant and Wild-Type Gastrointestinal Stromal Tumors (GISTs) with Clinicopathological Correlation |
| title_sort | Molecular Profiling of KIT/PDGFRA-Mutant and Wild-Type Gastrointestinal Stromal Tumors (GISTs) with Clinicopathological Correlation |
| url | http://hdl.handle.net/11675/12201 http://www.scopus.com/inward/record.url?scp=85202516640&partnerID=8YFLogxK |