scholarly journals Unraveling the spectrum of KIT mutations in gastrointestinal stromal tumors: An Indian Tertiary Cancer Center Experience

2017 ◽  
Vol 06 (03) ◽  
pp. 113-117 ◽  
Author(s):  
Trupti Pai ◽  
Munita Bal ◽  
Omshree Shetty ◽  
Mamta Gurav ◽  
Vikas Ostwal ◽  
...  
Keyword(s):  
Gastrointestinal Stromal Tumors ◽  
Complete Analysis ◽  
Cancer Center ◽  
Kit Mutation ◽  
Stromal Tumors ◽  
Molecular Alterations ◽  
Kit Gene ◽  
Exon 9 ◽  
Substitution Mutations ◽  
Exon 11

Abstract Background: Primary mutations in the KIT gene are the driving force for gastrointestinal stromal tumors (GIST) tumorigenesis. Predictive role of KIT mutation status aids oncologists in patient management. There is a paucity of comprehensive data on the frequency of mutations in the KIT gene in GIST affecting Indian patients. The aims of this study were to determine the frequency and spectrum of molecular alterations affecting the KIT gene and assess their association with clinicopathologic features in a cohort of patients of GIST. Materials and Methods: Morphological and immunohistochemically confirmed GIST cases (n = 114) accessioned from August 2014-June 2015 were analyzed for mutations in KIT exons 9, 11, 13, and 17 and subjected to Sanger sequencing onto the ABI 3500 Genetic Analyzer. The sequences were analyzed using sequence analysis software: SeqScape® and Chromas Lite. Results: KIT mutations were seen in 70% of cases and the majority of KIT mutations involved exon 11 (57%), followed by exon 9 (10%), exon 13 (3%), and exon 17 (1%). Most common exon 11 mutations were in-frame deletions (61.4%) followed by substitution mutations (19.3%). Exon 9 mutations showed identical duplication of Ala-Tyr at codons 502–503. Simultaneous mutations affecting exon 11 and 13 were discovered. Novel variations, namely, p.Q556E (c.1666C>G), p.Q556dup (c.1666_1668dupCAG), p.K558_V559delinsS (c.1672_1677delAAGGTTinsAGT), p.Y503_F504insTY (c.1509_1510insACCTAT), and p.K642R (c.1925A>G) involving exons 11, 9, and 13, respectively, were observed. Interpretation and Conclusions: First study with complete analysis of all 4 exons of KIT (exons 9, 11, 13, and 17) in Indian GIST patients. Along with well-described KIT mutations, several rare double mutations as well as novel alterations were reported in this series.

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

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.

Laparoscopic surgery for familial multiple gastrointestinal stromal tumors with germ line c‐kit gene mutation

2020 ◽  
Author(s):  
Masahiro Hashimoto ◽  
Tsuyoshi Takahashi ◽  
Kiyokazu Nakajima ◽  
Yukinori Kurokawa ◽  
Yasuhiro Miyazaki ◽  
...  
Keyword(s):  
Laparoscopic Surgery ◽  
Gene Mutation ◽  
Gastrointestinal Stromal Tumors ◽  
Germ Line ◽  
Stromal Tumors ◽  
Kit Gene

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.

scholarly journals The importance of molecular biology in development, prognosis, treatment and resistance to targeted therapy in gastrointestinal stromal tumors

2011 ◽  
pp. 69-79
Author(s):  
Alessandro Comandone ◽  
Elisa Berno ◽  
Simona Chiadò Cutin ◽  
Antonella Boglione
Keyword(s):  
Tyrosine Kinase ◽  
Gastrointestinal Stromal Tumors ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Neoplastic Transformation ◽  
Response To Therapy ◽  
Mesenchymal Tumors ◽  
Kit Mutation ◽  
Stromal Tumors ◽  
Receive Treatment

Gastrointestinal stromal tumors (GISTs) are the commonest mesenchymal tumors of the gastroenteric tract, and are generally believed to originate from the neoplastic transformation of the interstitial cells of Cajal, the pacemaker structures of the stomach and intestine. Exon and genetic mutations (point/deletions) are fundamental for the development of GISTs: the constitutional characteristic of this neoplasm is the presence of the cell surface Kit receptor. Kit is the product of the proto-oncogene cKit, situated in chromosome 4. Ninety-eight percent of GISTs express mutated isoforms of Kit or of PDGFRA (Platelet growth factor receptor a). Kit mutation is the basic condition for autophosphorylation of tyrosine kinase residues in proteins. Autophosphorylation initiates pathogenetic processes in Cajal cells, toward a neoplastic transformation. Imatinib mesilate and, more recently, sunitinib are tyrosine kinase inhibitors, specific antagonists for Kit and PDGFRA, with good activity against GISTs. Most molecular and clinical data currently available concern imatinib. Exon mutations are strategic as prognostic and as predictive factors. In recent years, much evidence suggests that survival, response to therapy and resistance to imatinib are related to different mutations. In the near future, GIST patients will receive treatment differentiated by expressed Kit and PDGFRA mutations, thus truly individualized therapy.

scholarly journals Mutation status and immunohistochemical correlation of EGFR mutations in gastrointestinal stromal tumors

2021 ◽  
Vol 24 (1) ◽  
pp. 67-72
Author(s):  
H Ozkayalar ◽  
MC Ergoren ◽  
G Tuncel ◽  
S Kurt ◽  
E Cevik ◽  
...  
Keyword(s):  
Gastrointestinal Stromal Tumors ◽  
Kinase Inhibitors ◽  
Treatment Options ◽  
Growth Factor Receptor ◽  
Egfr Mutations ◽  
Stromal Tumors ◽  
Molecular Alterations ◽  
Treatment Regimes ◽  
Research Areas ◽  
Turkish Patients

Abstract Being one of the leading causes of cancer deaths worldwide and their resistance to conventional treatment methods, made gastrointestinal stromal tumors (GISTs) one of the hot topics in medical research areas in the past decade. To investigate molecular alterations underlying the tumor is of great importance to be able to develop new, targeted treatment options. In this study, GIST samples obtained from 40 Turkish patients were analyzed for actionable epidermal growth factor receptor (EGFR) mutations that are related to treatment regimes in non small cell lung cancer (NSCLC) to understand whether EGFR expression is altered in GISTs. Established alterations in EGFR can make the use of tyrosine kinase inhibitors possible, which are currently used in cancer therapy, especially in NSCLC. Our results indicated that EGFR mutations are rare in GISTs. Further research is needed to sequence whole coding regions of the gene to investigate new actionable mutations in EGFR in an increased sample size.

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