Molecular Profile of Gastrointestinal Stromal Tumors in Sixty-Eight Patients from a Single Swiss Institution

Haefliger, Simon; Marston, Katharina; Juškevičius, Darius; Meyer-Schaller, Nathalie; Förster, Anja; Nicolet, Stefan; Komminoth, Paul; Stauffer, Edouard; Cathomas, Gieri; Hoeller, Sylvia; Tornillo, Luigi; Dirnhofer, Stefan; Terracciano, Luigi; Bihl, Michel; Matter, Matthias S.

doi:10.1159/000505407

Cited by 8 publications

(3 citation statements)

References 25 publications

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“…Notably, we found that 11 of 74 cases (15%) ( Figure 3 ) harbored malignant BRAF-V600E mutations, which had not been detected in previous studies of small GISTs. These results contradict the previous studies which reported the mutation rate of BRAF ranges from 1~4% for large GISTs [ 31 ], suggesting that BRAF-mutated tumors might represent a low-risk subtype of small gastric GISTs. A previous study reported that 54.8% of BRAF-mutated GISTs, which were classified as intermediate or high risk [ 32 ], were located in the small bowel or colorectum, whereas stomach-derived tumors tended to have a low risk.…”

Section: Discussioncontrasting

confidence: 99%

Small Gastric Stromal Tumors: An Underestimated Risk

Guo

Yang

et al. 2022

Cancers

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Background and Objectives: Small gastrointestinal stromal tumors (GISTs) are defined as tumors less than 2 cm in diameter, which are often found incidentally during gastroscopy. There is controversy regarding the management of small GISTs, and a certain percentage of small GISTs become malignant during follow-up. Previous studies which used Sanger targeted sequencing have shown that the mutation rate of small GISTs is significantly lower than that of large tumors. The aim of this study was to investigate the overall mutational profile of small GISTs, including those of wild-type tumors, using whole-exome sequencing (WES) and Sanger sequencing. Methods: Thirty-six paired small GIST specimens, which were resected by endoscopy, were analyzed by WES. Somatic mutations identified by WES were confirmed by Sanger sequencing. Sanger sequencing was performed in an additional 38 small gastric stromal tumor samples for examining hotspot mutations in KIT, PDGFRA, and BRAF. Results: Somatic C-KIT/PDGFRA mutations accounted for 81% of the mutations, including three novel mutation sites in C-KIT at exon 11, across the entire small gastric stromal tumor cohort (n = 74). In addition, 15% of small GISTs harbored previously undescribed BRAF-V600E hotspot mutations. No significant correlation was observed among the genotype, pathological features, and clinical classification. Conclusions: Our data revealed a high overall mutation rate (~96%) in small GISTs, indicating that genetic alterations are common events in early GIST generation. We also identified a high frequency of oncogenic BRAF-V600E mutations (15%) in small GISTs, which has not been previously reported.

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Section: Discussioncontrasting

confidence: 99%

Small Gastric Stromal Tumors: An Underestimated Risk

Guo

Yang

et al. 2022

Cancers

View full text Add to dashboard Cite

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“…Notably, we found that 11 of 74 cases (15%) (Figure 3) harbored malignant BRAF-V600E mutations, which had not been detected in previous studies of small GISTs. These results contradict the previous studies which reported the mutation rate of BRAF ranges from 1~4% for large GISTs [31], suggesting that BRAF-mutated tumors might represent a low-risk subtype of small gastric GISTs. A previous study reported that 54.8% of BRAFmutated GISTs, which were classified as intermediate or high risk [32], were located in the small bowel or colorectum, whereas stomach-derived tumors tended to have a low risk.…”

Section: Discussioncontrasting

confidence: 99%

Small Gastric Stromal Tumors: An Underestimated Risk

Guo¹,

Ge²,

Yang³

et al. 2022

SSRN Journal

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“…Additional genomic/chromosomal alterations are required for tumor progression. Such aberrations have been studied by different techniques: banding analysis, fluorescence in situ hybridization (FISH), comparative genomic hybridization (CGH), array CGH, and high-throughput sequencing [ 8 – 14 ].…”

Section: Introductionmentioning

confidence: 99%

Cytogenetic and molecular analyses of 291 gastrointestinal stromal tumors: site-specific cytogenetic evolution as evidence of pathogenetic heterogeneity

et al. 2022

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Gastrointestinal stromal tumor (GIST) is a mesenchymal neoplasm with variable behavior. An increased understanding of the tumor pathogenesis may improve clinical decision-making. Our aim was to obtain more data about the overall chromosome aberrations and intratumor cytogenetic heterogeneity in GIST. We analyzed 306 GIST samples from 291 patients using G-banding, direct sequencing, and statistics. Clonal chromosome aberrations were found in 81% of samples, with 34% of 226 primary tumors demonstrating extensive cytogenetic heterogeneity. 135 tumors had simple (≤5 changes) and 91 had complex (>5 changes) karyotypes. The karyotypically complex tumors more often were non-gastric ( P < 0.001), larger ( P < 0.001), more mitotically active ( P = 0.009) and had a higher risk of rupture ( P < 0.001) and recurrence ( P < 0.001). Significant differences between gastric and non-gastric tumors were found also in the frequency of main chromosome losses: of 14q (79% vs. 63%), 22q (38% vs. 67%), 1p (23% vs. 88%), and 15q (18% vs. 77%). Gastric PDGFRA -mutated tumors, compared with gastric KIT -mutated, had a lower incidence of 22q losses (18% vs. 43%) but a higher rate of 1p losses (42% vs. 22%). The present, largest by far karyotypic study of GISTs provides further evidence for the existence of variable pathogenetic pathways operating in these tumors’ development.

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Molecular Profile of Gastrointestinal Stromal Tumors in Sixty-Eight Patients from a Single Swiss Institution

Cited by 8 publications

References 25 publications

Small Gastric Stromal Tumors: An Underestimated Risk

Small Gastric Stromal Tumors: An Underestimated Risk

Small Gastric Stromal Tumors: An Underestimated Risk

Cytogenetic and molecular analyses of 291 gastrointestinal stromal tumors: site-specific cytogenetic evolution as evidence of pathogenetic heterogeneity

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