scholarly journals Cutaneous Hyperpigmentation and Familial Gastrointestinal Stromal Tumor Associated with Germline KIT Mutation Treated with Imatinib

2020 ◽  
Author(s):  
Wei Yuan ◽  
Wen Huang ◽  
Lei Ren ◽  
Chen Xu ◽  
Lijuan Luan ◽  
...  
Keyword(s):  
Abdominal Pain ◽  
Gastrointestinal Stromal Tumor ◽  
Mutational Analysis ◽  
Direct Sequencing ◽  
Correct Diagnosis ◽  
Saliva Sample ◽  
Stromal Tumor ◽  
Imatinib Treatment ◽  
Kit Mutation ◽  
Exon 11

Abstract Background: Familial gastrointestinal stromal tumor (GIST) has been identified with multiple GISTs containing the mutations in germline KIT and PDGFRA. There are only 35 kindreds with germline KIT and 6 with PDGFRA mutations have been reported so far. Familial GIST is often characterized by a series of manifestations, such as multiple lesions, hyperpigmentation, mastocytosis, and dysphagia. Only some kindreds have response to imatinib treatment.Materials and Methods: A 25-year-old Chinese woman went to hospital because of the abdominal pain, and through the computed tomography (CT) scan showed us the multiple tumors in the small intestine. Her father had a history of multifocal GISTs, and referred to the hospital with abdominal pain and tumor recurrences last year. Immuhistochemical analysis of CD117 and DOG-1 were performed on tumor samples from the two patients, while KIT mutational analysis was carried out by direct sequencing on DNA from paraffin-embedded specimens and saliva sample.Results: Multiple GISTs associated with diffuse interstitial cells of Cajal (ICC) hyperplasia were illustrated in these two patients. These tumors were positive for CD117 and DOG-1. The germline mutation at codon 560 of exon 11 (p.V560G) of the KIT gene were found. The treatment with imatinib resulted in favorable responses in both tumor and cutaneous hyperpigmentation.Conclusions: It is difficult to make a correct diagnosis of familial GIST at first time for its rarity. This case was finally diagnosed as familial GIST depending on the combination of diffuse ICC hyperplasia, germline KIT mutation, hyperpigmentation and its family history.

scholarly journals Cutaneous Hyperpigmentation and Familial Gastrointestinal Stromal Tumor Associated With Germline KIT Mutation Treated With Imatinib: A Chinese Case Report

2020 ◽  
Author(s):  
Wei Yuan ◽  
Wen Huang ◽  
Lei Ren ◽  
Jinghuan Lv ◽  
Chen Xu ◽  
...  
Keyword(s):  
Abdominal Pain ◽  
Gastrointestinal Stromal Tumor ◽  
Mutational Analysis ◽  
Direct Sequencing ◽  
Correct Diagnosis ◽  
Stromal Tumor ◽  
Kit Mutation ◽  
History Of ◽  
Exon 11 ◽  
Cells Of Cajal

Abstract BackgroundFamilial gastrointestinal stromal tumor (GIST) has been identified with multiple GISTs harboring the mutations in germline KIT and PDGFRA. There are only 35 kindreds with germline KIT and 6 with PDGFRA mutations have been reported to date. Familial GIST is often characterized by a series of manifestations, such as multiple lesions, hyperpigmentation, mastocytosis, and dysphagia. Only some kindreds have response to imatinib treatment.Materials and MethodsA 25-year-old Chinese woman presented to the hospital with abdominal pain, and computed tomography (CT) scan showed multiple tumors in the small intestine. Her father had a history of multifocal GISTs, and referred to the hospital with abdominal pain and tumor recurrences last year. Immuhistochemical analysis of CD117 and DOG-1 were performed on tumor samples from the two patients, while KIT mutational analysis was carried out by direct sequencing on DNA from paraffin-embedded specimens and saliva sample.ResultsMultiple GISTs associated with diffuse interstitial cells of Cajal (ICC) hyperplasia were illustrated in these two patients. These tumors were positive for CD117 and DOG-1. The germline mutation at codon 560 of exon 11 (p.V560G) of the KIT gene were found. Treatment with imatinib resulted in favorable responses in both tumor and cutaneous hyperpigmentation.ConclusionsIt is difficult to make a correct diagnosis of familial GIST at first time due to its rarity. This case was finally diagnosed as familial GIST depending on the combination of diffuse ICC hyperplasia, germline KIT mutation, hyperpigmentation and its family history.

scholarly journals Recurrent gastrointestinal stromal tumor (GIST) of the stomach associated with a novel c-kit mutation after imatinib treatment

2006 ◽  
Vol 9 (3) ◽  
pp. 235-239 ◽  
Author(s):  
Tomoki Koyama ◽  
Hiroshi Nimura ◽  
Katsutoshi Kobayashi ◽  
Hideki Marushima ◽  
Hironori Odaira ◽  
...  
Keyword(s):  
Gastrointestinal Stromal Tumor ◽  
Stromal Tumor ◽  
Imatinib Treatment ◽  
Kit Mutation

scholarly journals Benefit of imatinib adjuvant therapy for patients with intermediate risk gastrointestinal stromal tumor: a multi-center retrospective analysis in China

2019 ◽  
Author(s):  
Fan Feng ◽  
Yong Fang ◽  
Jun Zhang ◽  
Guoliang Zheng ◽  
Qing Qiao ◽  
...  
Keyword(s):  
Gastrointestinal Stromal Tumor ◽  
Univariate Analysis ◽  
Disease Free Survival ◽  
Stromal Tumor ◽  
Imatinib Treatment ◽  
Intermediate Risk ◽  
Free Survival ◽  
Mutational Status ◽  
Exon 11 ◽  
Disease Free

Abstract Background The benefit of postoperative imatinib therapy on intermediated risk gastrointestinal stromal tumor patients were still under debate. Thus, the present study aims to investigate the impact of imatinib adjuvant therapy on the prognosis of intermediate risk gastrointestinal stromal tumor patients.Methods From January 2000 to April 2018, a total of 450 intermediate risk gastrointestinal stromal tumor patients received R0 resection from eight centers in China were enrolled. The clinicopathological features and prognosis of patients were analyzed. Discrete variables were analyzed using the Chi-square test or Fisher's exact test. Significant predictors for survival identified by univariate analysis and multivariate analysis. Disease-free survival was evaluated by Kaplan-Meier method.Results Among the 450 patients, 109 patients (24.2%) received imatinib treatment. The recurrence rate of patients with and without imatinib treatment was 7.3% and 5.3%, respectively. For the entire cohort, gene mutational status was the only independent risk factor for disease-free survival of patients though univariate and multivariate analysis (P=0.028). For patients without imatinib treatment, tumor location (P=0.025) and gene mutation status (P=0.040) were prognostic factors in univariate analysis. However, only gene mutational status was independent prognostic factor (P=0.037). The disease-free survival of gastrointestinal stromal tumor with exon 11 deletion mutation with and without imatinib treatment were comparable (P=0.531).Conclusions Imatinib adjuvant treatment could not improve the prognosis of intermediate risk gastrointestinal stromal tumors. Intermediate gastrointestinal stromal tumors with exon 11 deletion mutation or non-gastric location may be candidates for imatinib treatment.

Effect of Imatinib Mesylate in a Patient with a Metastatic Gastrointestinal Stromal Tumor with a c-kit Mutation in Exon 11

2007 ◽  
Vol 52 (7) ◽  
pp. 1725-1729 ◽  
Author(s):  
Keisuke Kubota ◽  
Atom Katayama ◽  
Yutarou Takeshita ◽  
Koji Nozaki ◽  
Tetsuya Ueda ◽  
...  
Keyword(s):  
Gastrointestinal Stromal Tumor ◽  
Imatinib Mesylate ◽  
Stromal Tumor ◽  
Kit Mutation ◽  
Exon 11

Epithelioid Gastrointestinal Stromal Tumor of the Stomach with Liver Metastases in a 12-Year-old Girl: Aspiration Cytology and Molecular Study

2002 ◽  
Vol 5 (4) ◽  
pp. 386-394 ◽  
Author(s):  
Peng Li ◽  
Jianjun Wei ◽  
A. Brian West ◽  
MaryAnn Perle ◽  
M. Alba Greco ◽  
...  
Keyword(s):  
Liver Metastasis ◽  
Gastrointestinal Stromal Tumor ◽  
Mutational Analysis ◽  
Cytogenetic Study ◽  
Normal Karyotype ◽  
Molecular Study ◽  
Stromal Tumor ◽  
Gastric Tumor ◽  
Autonomic Nerve ◽  
Kit Mutation

Gastrointestinal stromal tumor (GIST), a stromal tumor of the gastrointestinal tract defined as CD117 (c- kit)-positive neoplasm, occurs primarily in adults. GIST with CD117 (c- kit) mutation and certain cytogenetic abnormalities is associated with malignancy, though a definite relationship between prognosisand molecular alterations remains to be elucidated. We report the cytologic features of an epithelioid GIST arising in the stomach of a child and metastatic to the liver, and the molecular mutational analysis of both the primary gastric tumor and the liver metastasis. Literature of pediatric GISTs was also reviewed. Fine needle aspiration of the liver metastasis, processed by Ultrafast Papanicolaou stain, showed fragments of cohesive small epithelioid cells with bland oval nuclei and unipolar cytoplasm transected by capillaries. Immunohistochemically, all nodules in the stomach and liver expressed CD117 (c- kit). Interestingly, some of the gastric tumor clusters were uniformly CD34 positive, whereas others were uniformly CD34 negative, suggesting heterogeneity of tumor clones. The presence of neurosecretory granules further subtyped the tumor into gastric autonomic nerve tumor (GANT). Molecular mutational analysis, performed in both the gastric tumor and the liver metastasis, showed no sequence abnormality in exons 9, 11, and 13 of CD117 (c- kit). Cytogenetic study revealed normal karyotype. These features might suggest a different molecular mechanism leading to malignancy in certain GISTs arising in children.

Metastatic Gastrointestinal Stromal Tumor with an Exon 11 c-Kit Mutation Responding to the Tyrosine Kinase Inhibitor Imatinib

2004 ◽  
Vol 21 (1) ◽  
pp. 74-77 ◽  
Author(s):  
Haruhiko Cho ◽  
Osamu Kobayashi ◽  
Akira Tsuburaya ◽  
Yuka Sugiyama ◽  
Motonori Sairenji ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Gastrointestinal Stromal Tumor ◽  
Tyrosine Kinase Inhibitor ◽  
Kinase Inhibitor ◽  
Stromal Tumor ◽  
Kit Mutation ◽  
Exon 11

Critical Update and Emerging Trends in Imatinib Treatment for Gastrointestinal Stromal Tumor

2007 ◽  
Vol 2 (1) ◽  
pp. 43-48 ◽  
Author(s):  
Ugo De Giorgi ◽  
Alberto Pupi ◽  
Gina Turrisi ◽  
Iolanda Montenora ◽  
Stefano Morini ◽  
...  
Keyword(s):  
Gastrointestinal Stromal Tumor ◽  
Stromal Tumor ◽  
Imatinib Treatment ◽  
Emerging Trends

scholarly journals Combined Inhibition of AKT and KIT Restores Expression of Programmed Cell Death 4 (PDCD4) in Gastrointestinal Stromal Tumor

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3699
Author(s):  
Marya Kozinova ◽  
Shalina Joshi ◽  
Shuai Ye ◽  
Martin G. Belinsky ◽  
Dinara Sharipova ◽  
...  
Keyword(s):  
Cell Death ◽  
Gastrointestinal Stromal Tumor ◽  
Cell Lines ◽  
Synergistic Effects ◽  
Single Agent ◽  
Xenograft Model ◽  
Stromal Tumor ◽  
In Vivo Studies ◽  
Preclinical Model ◽  
Kit Mutation

The majority of gastrointestinal stromal tumor (GIST) patients develop resistance to the first-line KIT inhibitor, imatinib mesylate (IM), through acquisition of secondary mutations in KIT or bypass signaling pathway activation. In addition to KIT, AKT is a relevant target for inhibition, since the PI3K/AKT pathway is crucial for IM-resistant GIST survival. We evaluated the activity of a novel pan-AKT inhibitor, MK-4440 (formerly ARQ 751), as monotherapy and in combination with IM in GIST cell lines and preclinical models with varying IM sensitivities. Dual inhibition of KIT and AKT demonstrated synergistic effects in IM-sensitive and -resistant GIST cell lines. Proteomic analyses revealed upregulation of the tumor suppressor, PDCD4, in combination treated cells. Enhanced PDCD4 expression correlated to increased cell death. In vivo studies revealed superior efficacy of MK-4440/IM combination in an IM-sensitive preclinical model of GIST compared with either single agent. The combination demonstrated limited efficacy in two IM-resistant models, including a GIST patient-derived xenograft model possessing an exon 9 KIT mutation. These studies provide strong rationale for further use of AKT inhibition in combination with IM in primary GIST; however, alternative agents will need to be tested in combination with AKT inhibition in the resistant setting.

Multiple Bowel Perforations Complicating Imatinib Treatment for Advanced Gastrointestinal Stromal Tumor

2008 ◽  
Vol 206 (2) ◽  
pp. 386-387 ◽  
Author(s):  
Massimo Chiarugi ◽  
Christian Galatioto ◽  
Piero V. Lippolis ◽  
Massimo Seccia
Keyword(s):  
Gastrointestinal Stromal Tumor ◽  
Stromal Tumor ◽  
Imatinib Treatment

scholarly journals Successful Perioperative and Surgical Treatment of a Rare Case of Extra-Gastrointestinal Stromal Tumor Arising in the Prostate Gland

2019 ◽  
Vol 12 (1) ◽  
pp. 183-191 ◽  
Author(s):  
Patrick Schöffski ◽  
Raf Sciot ◽  
Maria Debiec-Rychter ◽  
Johan Van Ongeval ◽  
André D'Hoore ◽  
...  
Keyword(s):  
Gastrointestinal Stromal Tumor ◽  
Prostate Gland ◽  
Interstitial Cells ◽  
Stromal Tumor ◽  
Imatinib Treatment ◽  
Smooth Muscle Contractility ◽  
Double Mutation ◽  
Primary Gist ◽  
Common Precursor ◽  
Cells Of Cajal

We report a very uncommon case of a primary, non-metastatic gastrointestinal stromal tumor (GIST) arising in the prostate gland in a 60-year-old patient. The morphology and immunohistochemical profile of the disease resembled GIST of gastrointestinal origin, and the molecular driver of this malignancy was a double mutation in exons 11 and 13 of the KIT gene. The tumor was proliferating slowly, did respond to neoadjuvant therapy with the KIT-inhibiting agent imatinib and was cured by radical, retro-pubic prostatectomy followed by adjuvant imatinib treatment. We postulate that primary GIST tumors of the prostate can arise from prostatic interstitial cells, which are the pacemakers of smooth muscle contractility in the gland, and possibly share a common precursor with typical GIST and the interstitial cells of Cajal in the gastrointestinal tract.

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