Abdominal tumors in patients with neurofibromatosis type I: Genotype-phenotype relationships

Matas‐Nadal, Clara; Soria, Xavier Gimeno; Gonzalez-Farré, M; Baradad, M.; Tuset, N; Riu, Ferran Rius; González, Miguel; Gatius, Sònia; Vilardell, F.; López-Ortega, Ricard; Martí, Raquel

doi:10.1016/j.ejmg.2022.104609

Cited by 1 publication

(8 citation statements)

References 29 publications

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“…6,26,29 NF1-GISTs and SDH-GISTs are the most frequent wild-type GISTs without KIT and PDGFRA mutation in both adults and children, including adolescent and young adults (AYAs), respectively. 1,6,14,15 According to previous reports, [15][16][17] NF1-GISTs are predominantly found in the small intestine, are sometimes multicentric, and show spindle cell features, consistent with this report. NF1-GISTs are considered primarily refractory to all approved tyrosine kinase inhibitors, including imatinib, sunitinib, and regorafenib.…”

Section: Discussionsupporting

confidence: 91%

“…1,2 Most reports are series of wild-type GISTs but are not population based. [6][7][8][9][10][11][12][15][16][17]20,21 In our study, wild-type GISTs accounted for 7.7% Tumor size (mean ± SD; cm) 8.0 ± 7.9 6.9 ± 2.9 TA B L E 3 Clinicopathological features of wild-type GISTs according to genotyping.…”

Section: Discussionmentioning

confidence: 66%

“…However, most reports on wild-type GISTs are case series, and registry-based reports are rare-this study may be one of the largest. [6][7][8][9][10][11][12][15][16][17]20,21 Second, mutations found in the study included three SDH variants not reported in the ClinVar and COSMIC databases, indicating their unknown pathogenicity. However, these wild-type GISTs did not harbor other apparent potential driver mutations, which should be addressed by future studies.…”

Section: Discussionmentioning

confidence: 99%

“…Most NF1-GISTs were in the small intestine (N = 12; 75%), and 38% (6 out of 16 patients) had multiple tumors, as reported previously. [15][16][17] All NF1-GISTs but one showed the spindle cell type, and the proliferation activities appeared to be modest (mitosis count: 5.2 ± 5.4/50 HPF and Ki67: 4.7 ± 5.7%) compared with the other wild-type GISTs (Table 3). Nine NF1-GIST patients of 16 had multiple café au lait spots, and 10 patients had subcutaneous multiple neurofibromas (Table 1).…”

Section: Clinicopathological Features Of Gists With Nf1 Sdh or Braf M...mentioning

confidence: 98%

“…[6][7][8][9][10][11][12] Some wild-type GISTs may be presented in the context of syndromes with germline mutations involving the SDH complex or of the Carney triad associated with hypermethylation 13,14 and in the context of neurofibromatosis type 1 (NF1). [15][16][17] Nevertheless, as wild-type GIST is very rare, clinical and pathological features as well as prognostic outcomes are poorly understood.…”

Section: Introductionmentioning

confidence: 99%

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Molecular and clinicopathological features of KIT/PDGFRAwild‐type gastrointestinal stromal tumors

Nishida,

Naito,

Takahashi

et al. 2024

Cancer Science

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Approximately 10% of gastrointestinal stromal tumors (GISTs) harbor reportedly no KIT and PDGFRA mutations (wild‐type GISTs). The clinicopathological features and oncologic outcomes of wild‐type GISTs based on molecular profiles are unknown. We recruited 35 wild‐type GIST patients from the two registry studies of high‐risk GISTs between 2012 and 2015 and primary GISTs between 2003 and 2014. Molecular profiling of wild‐type GISTs was performed by targeted next‐generation sequencing (NGS) using formalin‐fixed paraffin‐embedded tumor samples. Among 35 wild‐type GISTs, targeted NGS analysis detected NF1, SDH, or BRAF mutation: 16 NF1‐GISTs with various NF1 mutations, 12 SDH‐GISTs (4 with SDHA mutations, 4 with SDHB mutations, and 4 with SDHB‐negative staining), and 5 BRAF‐GISTs with the V600E mutation. Two GISTs showed no mutations based on our targeted NGS analysis. Additional gene mutations were infrequent in primary wild‐type GISTs and found in TP53, CREBBP, CDKN2A, and CHEK2. Most NF1‐GISTs were located in the small intestine (N = 12; 75%) and showed spindle cell features (N = 15; 94%) and multiple tumors (N = 6, 38%) with modest proliferation activities. In contrast, SDH‐GISTs were predominantly found in the stomach (N = 11; 92%), exhibiting epithelioid cell (N = 6; 50%) and multiple (N = 6, 50%) features. The overall survival of patients with SDH‐GISTs appeared to be better than that of BRAF‐GISTs (p = 0.0107) or NF1‐GISTs (p = 0.0754), respectively. In conclusion, major molecular changes in wild‐type GISTs include NF1, SDH, and BRAF. NF1‐GISTs involved multifocal spindle cell tumors in the small intestine. SDH‐GISTs occurred in young patients and were multifocal in the stomach and clinically indolent.

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