Clinicopathological and molecular features of a large cohort of gastrointestinal stromal tumors (GISTs) and review of the literature: BRAF mutations in KIT/PDGFRA wild-type GISTs are rare events

Huss, Sebastian; Pasternack, Helen; Ihle, Michaela A.; Merkelbach‐Bruse, Sabine; Heitkötter, Birthe; Hartmann, Wolfgang; Trautmann, Marcel; Gevensleben, Heidrun; Büttner, Reinhard; Schildhaus, Hans–Ulrich; Wardelmann, Eva

doi:10.1016/j.humpath.2017.01.005

Cited by 55 publications

(57 citation statements)

References 40 publications

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“…More than 80% of primary tumors harbor mutations in the KIT or PDGFRA proto-oncogene [6,8]. Several phase II trials have demonstrated the safety and efficacy of preoperative imatinib, and if an imatinib-sensitive mutation is present, the drug is the first choice for neoadjuvant treatment.…”

Section: Preoperative Treatment Of Locally Advanced Gistmentioning

confidence: 99%

“…Imatinib is active in GIST with mutations in the exon 11 and 9 of KIT gene and non-D842V PDGFRA mutations which comprise more than 80% of all primary tumors [8]. Imatinib is not active in exon 13, 14 and 17 mutations of KIT, in D842V PDGFR mutations, and in BRAF-mutated GIST, which comprise another 15% of all tumors.…”

Section: Preoperative Treatment Of Locally Advanced Gistmentioning

confidence: 99%

“…Approximately 80% of GIST tumors have a gain-of-function mutation of the c-kit or PDGF receptor [6,7,8]. Targeted therapy with the small-molecule RTKI imatinib has led to a dramatic improvement of the prognosis of patients with metastatic GIST [9,10,11].…”

Section: Introductionmentioning

confidence: 99%

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Neoadjuvant Therapy to Downstage the Extent of Resection of Gastrointestinal Stromal Tumors

Jakob¹,

Hohenberger²

2018

Visc Med

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Introduction: Gastrointestinal stromal tumors (GIST) are rare malignant tumors in terms of incidence, and they are not linked to specific symptoms. Often, primary tumors, particularly of the stomach, rectum, or rectovaginal space, are quite large when detected, and multivisceral resection seems to be the treatment of choice as the mainstay of therapy is complete tumor removal. If a gain-of-function mutation in the KIT gene is present, drug therapy with receptor tyrosine kinase inhibitors (RTKIs) might significantly downstage primary GIST tumors. Methods: A review of the literature was performed to identify the current evidence for preoperative treatment of GIST regarding toxicity, efficacy, and oncological outcome, including mutational data from our own database. Results: Four phase II as well as several cohort studies showed acceptable toxicity and no increased perioperative morbidity of preoperative imatinib. Progressive disease during preoperative treatment was a rare event, and partial response was achieved in 40-80% of all patients. For methodological reasons, the trials cannot prove an oncological long-term superiority of preoperative treatment. Conclusion: Preoperative therapy with imatinib is safe and recommended for patients with locally advanced GIST. Neoadjuvant imatinib therapy may enable less invasive and organ-sparing surgery, avoid tumor rupture during extensive resectional procedures, and improve the quality of perioperative RTKI treatment.

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Section: Preoperative Treatment Of Locally Advanced Gistmentioning

confidence: 99%

Section: Preoperative Treatment Of Locally Advanced Gistmentioning

confidence: 99%

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Neoadjuvant Therapy to Downstage the Extent of Resection of Gastrointestinal Stromal Tumors

Jakob¹,

Hohenberger²

2018

Visc Med

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“…However, the precise incidence of each rare subtype is unknown, although SDH-deficient GIST is the most frequent wild-type GIST. Each molecular subtype may have some specific features including location, clinical presentation and pathological characteristics as shown in Table 1, though, they are based on small retrospective studies (6)(7)(8)(9)(10)(11)(12)(13). Wild-type GISTs consistently express KIT tyrosine kinase, however, KIT and PDGFRA tyrosine kinases are, typically, not activated because the kinases lack auto-activation mechanisms, such as gain-of-function mutations or autocrine-loop.…”

mentioning

confidence: 99%

“…The several reports including Weldon et al suggest that, compared with KIT or PDGFRA-mutated GISTs, wild-type GISTs are generally indolent in clinicopathological features and show relatively good prognosis even after recurrence (5)(6)(7)(8)(9)(10)(11)(12)(13). Limited resection, taking account of organ-function, is recommended for primary wild-type GIST, and roles of surgery are limited for recurrent disease of wild-type GIST.…”

mentioning

confidence: 99%

Therapeutic strategies for wild-type gastrointestinal stromal tumor: is it different from KIT or PDGFRA-mutated GISTs?

Nishida¹

2017

Transl. Gastroenterol. Hepatol.

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Gastrointestinal stromal tumors with BRAF gene fusions. A report of two cases showing low or absent KIT expression resulting in diagnostic pitfalls

Torrence

Xie

Zhang

et al. 2021

Genes Chromosomes & Cancer

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Clinicopathological and molecular features of a large cohort of gastrointestinal stromal tumors (GISTs) and review of the literature: BRAF mutations in KIT/PDGFRA wild-type GISTs are rare events

Cited by 55 publications

References 40 publications

Neoadjuvant Therapy to Downstage the Extent of Resection of Gastrointestinal Stromal Tumors

Neoadjuvant Therapy to Downstage the Extent of Resection of Gastrointestinal Stromal Tumors

Therapeutic strategies for wild-type gastrointestinal stromal tumor: is it different from KIT or PDGFRA-mutated GISTs?

Gastrointestinal stromal tumors with BRAF gene fusions. A report of two cases showing low or absent KIT expression resulting in diagnostic pitfalls

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