scholarly journals Not all KIT 557/558 codons mutations have the same prognostic impact: breaking the exon 11 mutations in Gastrointestinal Stromal Tumors

Qeios ◽  
2022 ◽  
Author(s):  
Antonio Russo
Keyword(s):  
Gastrointestinal Stromal Tumors ◽  
Prognostic Impact ◽  
Stromal Tumors ◽  
Exon 11

Gastrointestinal Stromal Tumors With KIT Exon 11 Deletions Are Associated With Poor Prognosis

2006 ◽  
Vol 130 (6) ◽  
pp. 1573-1581 ◽  
Author(s):  
Johanna Andersson ◽  
Per Bümming ◽  
Jeanne M. Meis–Kindblom ◽  
Harri Sihto ◽  
Nina Nupponen ◽  
...  
Keyword(s):  
Gastrointestinal Stromal Tumors ◽  
Poor Prognosis ◽  
Stromal Tumors ◽  
Exon 11

Imatinib in the Management of Multiple Gastrointestinal Stromal Tumors Associated With a Germline KIT K642E Mutation

2007 ◽  
Vol 131 (9) ◽  
pp. 1393-1396
Author(s):  
Janet Graham ◽  
Maria Debiec-Rychter ◽  
Christopher L. Corless ◽  
Robin Reid ◽  
Rosemarie Davidson ◽  
...  
Keyword(s):  
Gastrointestinal Stromal Tumors ◽  
Interstitial Cells Of Cajal ◽  
Germline Mutations ◽  
Mesenchymal Tumors ◽  
Stromal Tumors ◽  
Pdgfra Gene ◽  
Oncogenic Mutations ◽  
Esophageal Tumors ◽  
Exon 11 ◽  
Cells Of Cajal

Abstract Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gut and are distinguished by expression of CD117 (c-Kit). Oncogenic mutations in the KIT or PDGFRA gene are detected in approximately 85% of sporadic GISTs. In recent years, examples of familial GIST have been reported in which germline mutations of KIT or PDGFRA result in multiple GISTs, skin disorders, and other abnormalities. The most common germline mutations are in KIT exon 11, mutations in exons 8 and 17 have also been described, and there are 2 families with germline PDGFRA mutations. We present a case in which a germline KIT exon 13 mutation (K642E) was discovered in a patient with multiple GISTs of rectum, small intestine, and esophagus, as well as diffuse hyperplasia of the interstitial cells of Cajal. To our knowledge, this is only the second germline example of this particular mutation. The patient's esophageal tumors were stabilized with imatinib.

Abstract 3107: A single ddPCR assay to detect KIT exon 11 mutations in tumor and cell free plasma DNA of patients with gastrointestinal stromal tumors

2016 ◽  
Author(s):  
Pieter A. Boonstra ◽  
Marco Tibbesma ◽  
Lisette J. Bosman ◽  
Ron H.J. Mathijssen ◽  
Frits van Coevorden ◽  
...  
Keyword(s):  
Gastrointestinal Stromal Tumors ◽  
Plasma Dna ◽  
Stromal Tumors ◽  
Exon 11 ◽  
Free Plasma

Pharmacokinetics of escalated dose of imatinib in patients with advanced gastrointestinal stromal tumors.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10085-10085
Author(s):  
Changhoon Yoo ◽  
Min-Hee Ryu ◽  
Baek-Yeol Ryoo ◽  
Inkeun Park ◽  
Mo Youl Beck ◽  
...  
Keyword(s):  
Dose Escalation ◽  
Gastrointestinal Stromal Tumors ◽  
Standard Dose ◽  
Progression Free Survival ◽  
Hematologic Toxicity ◽  
Pharmacokinetic Data ◽  
Stromal Tumors ◽  
Percent Change ◽  
Liquid Chromatography Tandem Mass ◽  
Exon 11

10085 Background: Although escalated dose (ED, 800 mg daily) of imatinib (IM) is one of important options in resistant gastrointestinal stromal tumors (GIST) on standard dose (SD, 400mg daily), there has been lack of pharmacokinetic data at ED. We therefore explore the potential relationship between IM plasma trough level (Cmin), and clinical outcomes or toxicities in patients treated with ED. Methods: Between 2008 and 2011, steady-state IM Cmin was measured in 66 patients with GIST who received ED of IM using liquid chromatography-tandem mass spectrometry. Percent change from IM Cmin at SD was calculated in 43 patients that both SD and ED IM Cmin were measured. The association with efficacy and toxicity was analyzed with grouping patients into quartiles according to IM Cmin at ED and percent change. Results: Median age was 59 years (range, 36–77) and 40 patients were male. KIT exon 11 and 9 mutation was detected in 32 and 18 patients, respectively. At ED, partial response was achieved in 4 patients (6%) and stable disease was in 32 patients (48%). The median progression-free survival was 4.2 months (95% CI, 1.8-6.6) and overall survival was 38.5 months (95% CI, 7.6-69.3). The mean (± standard deviation) IM Cmin at ED was 3552 (± 1540) ng/mL. IM Cmin was significantly increased after dose escalation (p <0.001), and mean percent change from IM Cmin at SD was 162% (± 100). Body surface area (p=0.01), hemoglobin (p=0.001), and neutrophil count (p=0.006) were significant covariates for IM Cmin at ED in multivariate analysis. The group of quartiles of IM Cmin at ED and percent change was not associated with response and survival outcomes. However, grade 3-4 hematologic or grade 2-4 non-hematologic toxicity was observed in 9% (1/11) of patients in the lowest percent change quartile (Q1, <90%) compared with 56% (18/32) in Q2 to Q4 (p=0.012), although absolute values were not associated with toxicity. Conclusions: In GIST patients treated with ED of IM, IM Cmin was not associated with response and survival. Clinically significant toxicity following dose escalation was correlated with percent change of IM Cmin, rather than absolute values. Monitoring of IM Cmin might help to predict or manage ED of IM induced toxicity.

Mutations in Exon 11 of the c-kit Gene in a Myogenic Tumor and a Neurogenic Tumor as Well as in Gastrointestinal Stromal Tumors

2003 ◽  
Vol 20 (3) ◽  
pp. 183-191 ◽  
Author(s):  
Rie Yasuoka ◽  
Chohei Sakakura ◽  
Katsumi Shimomura ◽  
Yoshifumi Fujita ◽  
Masayoshi Nakanishi ◽  
...  
Keyword(s):  
Gastrointestinal Stromal Tumors ◽  
Neurogenic Tumor ◽  
Stromal Tumors ◽  
Kit Gene ◽  
Exon 11

scholarly journals Gastrointestinal stromal tumors (gists): Definition, clinical, histological, immunohistochemical and molecular genetic features and predictors of malignant potential and differential diagnosis

2002 ◽  
Vol 10 (4) ◽  
pp. 267-271 ◽  
Author(s):  
Vesna Zivkovic ◽  
Vuka Katic ◽  
Aleksandar Nagorni ◽  
Ljubinka Velickovic ◽  
Maja Milentijevic ◽  
...  
Keyword(s):  
Gastrointestinal Stromal Tumors ◽  
Molecular Genetic ◽  
Malignant Potential ◽  
Gi Tract ◽  
Mesenchymal Tumors ◽  
Stromal Tumors ◽  
Cellular Origin ◽  
Genetic Features ◽  
Exon 11 ◽  
Malignant Gists

Gastrointestinal stromal tumors (GISTs) represent a distinct and the most important subset of mesenchymal tumors of the gastrointestinal (GI) tract GISTs occur throughout the GI tract but are usually located in the stomach and small intestine. The cellular origin, differentiation, nomenclature and prognosis of GISTs are controversial. Because GISTs, like the interstitial cells of Cajal, the GI pacemaker cells, express CD117 (c-kit protein), the origin of GISTs from the Cajal cells has recently been suggested. GISTs are also known for their wide variability in clinical behavior and for the difficulty to determine their malignant condition The most reproducible predictors of malignancy are mitotic count >1-5 per10 high-powered fields (HPF), size >5 cm, tumor necrosis, infiltration and metastasis to other sites. However, some tumors with mitotic activity <1/10 HPF may metastasize indicating some uncertainty in malignant potential of GISTs, especially those larger than 5 cm. Recently, mutations in c-kit gene (exon 11) preferentially occur in malignant GISTs and may be a clinically useful adjunct marker in evaluation of GISTs. In conclusion, the strong CD117 expression mostly defines primary GI mesenchymal tumors as GIST. Specific identification of GIST may become clinically important if therapies targeting the c-kit tyrosine kinase activation become available.

The real world outcomes of 3-year adjuvant therapy with imatinib in patients with high-risk molecular profiled gastrointestinal stromal tumors (GIST).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e23524-e23524
Author(s):  
Piotr Rutkowski ◽  
Marcin Zietek ◽  
Bozena Cybulska-Stopa ◽  
Joanna Streb ◽  
Stanislaw Gluszek ◽  
...  
Keyword(s):  
Clinical Trials ◽  
High Risk ◽  
Adjuvant Therapy ◽  
Real World ◽  
Gastrointestinal Stromal Tumors ◽  
Disease Relapse ◽  
Adjuvant Imatinib ◽  
Stromal Tumors ◽  
Exon 9 ◽  
Exon 11

e23524 Background: The real-world data on outcomes of adjuvant therapy in high-risk gastrointestinal stromal tumors (GIST) are very limited. Methods: We have analyzed the data of 107 consecutive patients (52 male, 56 female) with GIST after resection treated with adjuvant imatinib (for planned 3 years with initial dose 400 mg daily, started not later than 4 months after operation) in 6 oncological centers in 2013-2018. All patients were required to have high risk of recurrence (at least 50% according to NCCN/AFIP criteria), known mutational status to exclude PDGFRA D842V mutants and KIT/PDGFRA-wild type cases from therapy. Median follow-up time was 24 months. Results: The most common primary localization of GIST was small bowel (63 patients; 59%), followed by the stomach (40 patients; 37%). The majority of GIST cases harbored exon 11 KIT mutations (88 cases, 82%), 11 cases had exon 9 KIT mutations (10%), 8 had other KIT/PDGFRA mutations potentially sensitive to imatinib. Thirty three patients (31%) finished 3-year adjuvant imatinib therapy as planned, 59 (55%) still continue therapy, 4 (4%) patients had finished adjuvant therapy prematurely due to toxicity, 6 (6%) due to disease progression on treatment and 5 (4%) due to other reasons. The disease relapse was detected in 16 patients, of them in 4 cases in exon 9 KIT mutants (36%), and 10 cases in patients with exon 11 KIT mutations (11%) [p < 0.05]. Estimated 4-year relapse-free survival (RFS) rate is 78%. Conclusions: The early results of adjuvant therapy with imatinib in routine practice outside clinical trials in high-risk mutation-drive GIST patients only confirm high efficacy of this therapy with better tolerability than in clinical trials. Moreover, overrepresentation of exon 9 KIT mutants in a group of patients with disease relapse may indicate that standard 400 mg dose in adjuvant treatment is not sufficient for prevention of disease relapse.

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