<i><scp>EGFR</scp></i> gene mutation in gastrointestinal stromal tumours

Shi, Shanshan; Wu, Nan; He, Yan; Xue, Wei; Xia, Qiuyuan; Wang, Xuan; Ye, Sheng-Bin; Li, Rui; Rao, Qiu; Zhou, Xiaojun

doi:10.1111/his.13251

Cited by 15 publications

(13 citation statements)

References 19 publications

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“…Among these mutations, D770_N771insG and T790M occurred together with KIT , NRAS , or AKT1 mutations, whereas only the S752I/F mutation was harbored by KIT / PDGFRA WT GISTs. This result may overturn the hypothesis of Shi et al 19 that EGFR mutations are mutually exclusive with KIT , PDGFRA , KRAS , or BRAF mutations in primary GISTs. In addition, the EGFR mutation frequency detected in our study is higher compared with previous reports.…”

Section: Discussionsupporting

confidence: 57%

“… 18 However, there are very few literature on EGFR mutation in GISTs. 19 In the present study, 4 EGFR mutations (D770_N771insG, T790M, and S752I/F) were detected among the 40 GISTs. Among these mutations, D770_N771insG and T790M occurred together with KIT , NRAS , or AKT1 mutations, whereas only the S752I/F mutation was harbored by KIT / PDGFRA WT GISTs.…”

Section: Discussionsupporting

confidence: 46%

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Oncogene mutational analysis in Chinese gastrointestinal stromal tumor patients

Chen

Zhang

et al. 2018

OTT

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BackgroundGastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors and exhibit a high frequency of oncogenic KIT or PDGFRA mutations. Tyrosine kinase inhibitors (TKIs) have been mainly used in the treatment of GISTs bearing KIT/PDGFRA mutations. However, other mutation profiles have been found to affect the sensitivity to and effectiveness of TKIs in the treatment of GISTs.PurposeThe aim of the present study was to describe the mutational status of multiple genes in GIST samples and to provide information for finding potential predictive markers of therapeutic targets in Chinese GIST patients.Patients and methodsMassARRAY spectrometry was used to test 40 Chinese GIST patients for 238 mutations affecting 19 oncogenes.ResultsA total of 14 oncogenes with 43 mutations were detected in 38 samples, with a mutation frequency of 95%. Among these mutation samples, 26 GISTs were found for KIT or PDGFRA mutations, while 12 were KIT/PDGFRA wild-type. Approximately half of the GIST samples harbored multiple mutations. The most frequent mutations were found in KIT (62.5%), CDK4 (17.5%), NRAS (15%) and EGFR (12.5%). Other mutations included PIK3CA and AKT1 (10%), BRAF and ABL1 (7.5%), PDGFRA, ERBB2 and HRAS (5%), and AKT2, FLT3 and KRAS (2.5%). New mutated genes (CDK4, AKT2, FLT3, ERBB2, ABL1 and AKT1), a higher BRAF mutation frequency (7.5%) and new BRAF mutation sites (G464E) were found in Chinese GIST patients.ConclusionThis study demonstrated useful mutations in a small fraction of Chinese GIST, but targeted therapeutics on these potential predictive markers need to be investigated in depth especially in Oriental populations.

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Section: Discussionsupporting

confidence: 57%

Section: Discussionsupporting

confidence: 46%

Oncogene mutational analysis in Chinese gastrointestinal stromal tumor patients

Chen

Zhang

et al. 2018

OTT

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“…58 Additional genetic categories subsequently emerged, including succinate dehydrogenase (SDH)deficient GIST, 59,60 GIST with bi-allelic NF1 inactivation 61 and BRAF V600E-mutant GIST. 62,63 Exceptionally rare genetic alterations have also been reported, including EGFR mutations 64 and FGFR1, NTRK3 65 and ALK gene fusions. 66 Some genetic subtypes have predilections for particular locations within the gastrointestinal tract: for example, NF1-inactivated GIST occurs almost exclusively in the small intestine, while SDH-deficient GIST occurs almost exclusively in the stomach.…”

Section: Gastrointestinal Stromal Tumoursmentioning

confidence: 99%

Recent developments in gastroesophageal mesenchymal tumours

Papke

Hornick

2020

Histopathology

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The pathologist’s approach to gastroesophageal mesenchymal tumours has changed dramatically during the last 25 years. In particular, gastrointestinal stromal tumour (GIST) has evolved from a wastebasket mesenchymal tumour category to a precisely defined entity with an increasingly detailed genetic subclassification. This subclassification has brought gastrointestinal mesenchymal neoplasia into the realm of precision medicine, with specific treatments optimised for particular genetic subtypes. Molecular genetic data have also greatly improved our understanding of oesophageal mesenchymal tumours, including the discovery that so‐called ‘giant fibrovascular polyps’ in fact represent a clinically distinctive presentation of well‐differentiated liposarcoma. Here, we will focus on gastroesophageal mesenchymal tumours for which there have been recent developments in classification, molecular genetics or tumour biology: granular cell tumour, ‘giant fibrovascular polyp’/well‐differentiated liposarcoma, plexiform fibromyxoma, gastroblastoma and, of course, GIST.

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“…In addition to the mutations in well-known key driver genes, including KIT and PDGFRA, recent studies have revealed genetic alterations of other tumor-related genes in GISTs. For instance, EGFR mutations are found in 0.93% (3/323) of primary GISTs, and do not overlap with mutations in KIT, PDGFRA, KRAS or BRAF (89). EGFR mutations are associated with a stomach location, female gender and low recurrence rate.…”

Section: Other Gene Mutations In Gistmentioning

confidence: 99%

Molecular characterization and pathogenesis of gastrointestinal stromal tumor

Niinuma¹,

Suzuki²,

Sugai³

2018

Transl. Gastroenterol. Hepatol.

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Most gastrointestinal stromal tumors (GISTs) harbor activating mutations in the receptor tyrosine kinase gene or platelet-derived growth factor receptor alpha (), and the resultant activation of downstream signals plays a pivotal role in the development of GISTs. The sites of the tyrosine kinase gene mutations are associated with the biological behavior of GISTs, including risk category, clinical outcome and drug response. Mutations in RAS signaling pathway genes, including KRAS and BRAF, have also been reported in wild-type GISTs, though they are rare. Neurofibromin 1 () is a tumor suppressor gene mutated in neurofibromatosis type 1. Patients with mutations are at high risk of developing GISTs. Recent findings suggest that altered expression or mutation of members of succinate dehydrogenase (SDH) heterotetramer are causally associated with GIST development through induction of aberrant DNA methylation. At present, GISTs with no alterations in, RAS signaling genes or SDH family genes are referred to as true wild-type GISTs. and mutations are thought as the earliest events in GIST development, and subsequent accumulation of chromosomal aberrations and other molecular alterations are required for malignant progression. In addition, recent studies have shown that epigenetic alterations and noncoding RNAs also play key roles in the pathogenesis of GISTs.

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EGFR gene mutation in gastrointestinal stromal tumours

Abstract: We first established that GISTs carrying EGFR mutation are relatively benign tumours. Although EGFR mutations were rarely present in GIST, EGFR seems to play a significant role in the development and progression of GIST.

Cited by 15 publications

References 19 publications

Oncogene mutational analysis in Chinese gastrointestinal stromal tumor patients

Oncogene mutational analysis in Chinese gastrointestinal stromal tumor patients

Recent developments in gastroesophageal mesenchymal tumours

Molecular characterization and pathogenesis of gastrointestinal stromal tumor

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