scholarly journals Specify PDGFRA Mutation

2020 ◽  
Author(s):  
Keyword(s):  
Pdgfra Mutation

Prognostic relevance of genetic aberrations in gastrointestinal stromal tumors.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 49-49
Author(s):  
N. N. Mazurenko ◽  
I. S. Beliakov ◽  
I. V. Tsyganova ◽  
E. M. Bardina ◽  
O. A. Anurova ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Point Mutation ◽  
Prognostic Significance ◽  
Specific Gene ◽  
Wild Type ◽  
Kit Mutation ◽  
Genetic Aberrations ◽  
Pdgfra Mutation ◽  
Prognostic Relevance ◽  
Exon 11

49 Background: Gastrointestinal stromal tumours (GISTs) contain oncogenic KIT or PDGFRA tyrosine kinase (TK) mutations leading to disturbance of downstream signaling pathways that contribute to GIST pathogenesis. Additional genetic aberrations were found in GISTs, demonstrating the involvement of other genes important in tumor progression. The aim of the study was to evaluate the prognostic relevance of different TK mutations in GISTs and to analyze the additional genetic aberrations in GISTs according to mutational status. Methods: 180 GIST patients were examined for KIT (9, 11, 13, 17 exons) and PDGFRA mutations (12, 14, 18 exons) by direct sequencing of DNA obtained from microdissected tumor sections. Tumor tissue DNA from 44 GISTs patients was screened for loss of heterozygosity (LOH) at 11 microsatellite loci on 1p, 9p, 14q, 15q and 22q arms. Results: KIT and PDGFRA mutations were identified in 76.1% and 10% of GISTs, respectively. 13.9% GISTs had no mutations (wild type). Most of KIT mutations were located in exon 11 (65%) and exon 9 (9.4%). Prognostic significance of TK mutations was evaluated. There was a trend of better survival for patients with PDGFRA mutation then with KIT mutation or wild type GISTs. The higher overall survival prior to target therapy was shown for patients with duplication or point mutation in KIT exon 11 in comparison to exon 11 deletion. Analysis of LOH revealed allelic deletions in 85% of GISTs, more frequently at 14q arm. There was a different LOH pattern in subgroups of GISTs. GISTs with PDGFRA mutation and with KIT exon 11 point mutation had LOH at 14q, while GISTs with KIT exon 11 deletions revealed high LOH frequency also on 22q, 15q and 1p arms. LOH in wild type GISTs occurred on all chromosomes with low frequency. LOH on 9p was found exclusively in metastatic and recurrent GISTs. Specific gene loci of frequent LOH were identified on 9p, 15q and 22q that may be contributed to GIST progression. Conclusions: Specific mutations are associated with GISTs prognosis. Tumors with point mutations and duplications in KIT exon 11 are associated with a better survival then GISTs with other KIT mutations. Specific pattern of allelic deletions was identified in subgroups of GISTs according to type of mutation and tumor progression. No significant financial relationships to disclose.

scholarly journals Gastrointestinal Stromal Tumors: A Review of Case Reports, Diagnosis, Treatment, and Future Directions

2012 ◽  
Vol 2012 ◽  
pp. 1-16 ◽  
Author(s):  
Christopher B. Tan ◽  
Wanqing Zhi ◽  
Ghulamullah Shahzad ◽  
Paul Mustacchia
Keyword(s):  
Molecular Biology ◽  
Drug Research ◽  
Case Reports ◽  
Tissue Growth ◽  
Signaling System ◽  
First Line ◽  
Future Directions ◽  
Stromal Tumors ◽  
Pdgfra Mutation

Gastrointestinal stromal tumor (GIST) is a nonepithelial, mesenchymal tumor first described by Mazur and Clark in 1983. Since then, its molecular biology has been studied in great detail. Special interest in the role of tyrosine kinase in its regulation has been the target by different drug research. Mutation in c-kit exons 9, 11, 13, 17 and PDGFRA mutation in exons 12, 14, 18 are responsible for activation of gene signaling system resulting in uncontrolled phosphorylation and tissue growth. However, 5 to 15% of GISTs does not harbor these mutations, which raises additional questions in another alternate signaling pathway mutation yet to be discovered. Diagnosis of GISTs relies heavily on KIT/CD117 immunohistochemical staining, which can detect most GISTs except for a few 3% to 5% that harbors PDGFRA mutation. Newer staining against PKC theta and DOG-1 genes showed promising results but are not readily available. Clinical manifestation of GISTs is broad and highly dependent on tumor size. Surgery still remains the first-line treatment for GISTs. The advancement of molecular biology has revolutionized the availability of newer drugs, Imatinib and Sunitinib. Together with its advancement is the occurrence of Imatinib/Sunitinib drug resistance. With this, newer monoclonal antibody drugs are being developed and are undergoing clinical trials to hopefully improve survival in patients with GISTs.

Familial PDGFRA -mutation syndrome: somatic and gastrointestinal phenotype

2018 ◽  
Vol 76 ◽  
pp. 52-57 ◽  
Author(s):  
Paul N. Manley ◽  
Suzy Abu-Abed ◽  
Richard Kirsch ◽  
Andrea Hawrysh ◽  
Nicole Perrier ◽  
...  
Keyword(s):  
Pdgfra Mutation

scholarly journals The Novel Marker, DOG1, Is Expressed Ubiquitously in Gastrointestinal Stromal Tumors Irrespective of KIT or PDGFRA Mutation Status

2004 ◽  
Vol 165 (1) ◽  
pp. 107-113 ◽  
Author(s):  
Robert B. West ◽  
Christopher L. Corless ◽  
Xin Chen ◽  
Brian P. Rubin ◽  
Subbaya Subramanian ◽  
...  
Keyword(s):  
Gastrointestinal Stromal Tumors ◽  
The Novel ◽  
Mutation Status ◽  
Stromal Tumors ◽  
Pdgfra Mutation

ACRIN 6665/RTOG 0132 phase II trial of neoadjuvant imatinib mesylate (IM) for primary and recurrent operable malignant GIST: Imaging findings and correlation with genotype and GLUT4 expression

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 10552-10552
Author(s):  
A. D. Van den Abbeele ◽  
C. Gatsonis ◽  
D. J. de Vries ◽  
Y. Melenevsky ◽  
A. Szot Barnes ◽  
...  
Keyword(s):  
Metabolic Disease ◽  
Fdg Pet ◽  
Metabolic Response ◽  
Objective Response ◽  
Wild Type ◽  
Genotype 4 ◽  
Mutation Status ◽  
Pdgfra Mutation ◽  
Glut4 Expression ◽  
Exon 11

10552 Background: IM has improved the treatment of GIST patients (pts), but few achieve objective response despite significant clinical benefit. Imaging of tumor metabolism may provide earlier assessment of therapeutic response. In this study, FDG-PET metabolic response (MR) was compared with RECIST, GLUT4 expression, and KIT/PDGFRA mutation status. Methods: FDG-PET was done at baseline, 1–7 days, and 4 or 8 weeks (wk) after IM initiation. Best objective response was defined by RECIST. Immunohistochemical (IHC) tumor GLUT4 expression and mutation analyses were done at baseline and/or surgery. Background-subtracted SUVmax was measured in all lesions and summed; MR based on EORTC criteria was compared to RECIST, GLUT4 expression, and KIT/PDGFRA mutation status. Results: FDG-PET showed high tumor glycolytic activity at baseline (mean SUVmax = 14.2, range: 1.3–53.2), decreasing after 1 wk of IM (5.5, range: 0.5–47.7, p < 0.001, n = 44), and again prior to surgery (3.0, range: 0.5–36.1, p < 0.001, n = 40). FDG-PET response at wk 1 was 3 complete MR (CMR), 33 partial MR (PMR), 6 stable metabolic disease (SMD), and 2 progressive metabolic disease (PMD). Prior to surgery, FDG-PET response was 3 CMR, 33 PMR, 4 SMD, and no PMD. For 39 pts, RECIST best response was 2 PR, 36 SD, and 1 PD. GLUT4 expression decreased in 19 pts with PMR, and 3 with SMD. Among 12 pts with exon 11 mutation, 11 had PMR, 1 SMD; among 5 pts with wild-type genotype, 4 had PMR, and 1 SMD. Conclusions: After IM initiation, MR by FDG-PET was documented earlier (1–7 days), and was of much greater magnitude (36/40) than that documented by RECIST (2/39). IHC data suggest that: (1) GLUT4 plays a role in FDG uptake in GIST; (2) GLUT4 decreases in most pts with PMR; and, (3) the biologic action of IM interacts with glycolysis and GLUT4 expression. No difference in PMR was seen in pts with exon 11 vs. wild type mutations. [Table: see text]

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