Resected High-Risk Rectal GIST Harboring NTRK1 Fusion: a Case Report and Review of the Literature

Peixoto, Renata D’Alpino; Medeiros, Bruno Amaral; Cronemberger, Eduardo

doi:10.1007/s12029-020-00423-x

Cited by 8 publications

(6 citation statements)

References 13 publications

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“…Kinase-driven alterations, such as NTRK or FGFR fusion, have been recently reported in some GISTs [1][2][3][4][5][6][7][18][19][20][21][22][23]. The NTRK genes encode TRK proteins that exert oncogenic effects on tumors, and the activation of most TRK proteins is caused by NTRK fusions [8,9].…”

Section: Discussionmentioning

confidence: 99%

“…The NTRK genes encode TRK proteins that exert oncogenic effects on tumors, and the activation of most TRK proteins is caused by NTRK fusions [8,9]. NTRK fusions occur in a variety of cancers with different incidences [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23]. TRK inhibitors, such as Larotrectinib and Entrectinib, have shown encouraging antitumor efficacies in tumors with NTRK rearrangements and have been approved as treatments for multiple cancers harboring NTRK fusions [24][25][26][27][28][29][30].…”

Section: Discussionmentioning

confidence: 99%

“…The NTRK family consists of NTRK1, NTRK2, and NTRK3, which encode tropomyosin receptor kinase (TRK) [8,9]. NTRK fusion has been reported in many unrelated neoplasms, including infantile fibrosarcoma [10], mesoblastic nephroma [11], secretory breast carcinoma [12], mammary analog secretory carcinoma of the salivary gland [13], thyroid carcinoma [14], glioblastoma [15], cholangiocarcinoma [16], myofibroblast tumors [17], and WT GISTs [18][19][20][21][22][23]. Herein, we report a new case of quadruple WT with ETV6::NTRK3 gene fusion, a rare genetic event with only a few cases previously reported.…”

Section: Introductionmentioning

confidence: 99%

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ETV6::NTRK3 Fusion-Positive Wild-Type Gastrointestinal Stromal Tumor (GIST) with Abundant Lymphoid Infiltration (TILs and Tertiary Lymphoid Structures): A Report on a New Case with Therapeutic Implications and a Literature Review

Machado,

Claramunt-Alonso,

Lavernia

et al. 2024

IJMS

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Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract, with proto-oncogene, receptor tyrosine kinase (c-kit), or PDGFRα mutations detected in around 85% of cases. GISTs without c-kit or platelet-derived growth factor receptor alpha (PDGFRα) mutations are considered wild-type (WT), and their diverse molecular alterations and biological behaviors remain uncertain. They are usually not sensitive to tyrosine kinase inhibitors (TKIs). Recently, some molecular alterations, including neurotrophic tyrosine receptor kinase (NTRK) fusions, have been reported in very few cases of WT GISTs. This novel finding opens the window for the use of tropomyosin receptor kinase (TRK) inhibitor therapy in these subtypes of GIST. Herein, we report a new case of NTRK-fused WT high-risk GIST in a female patient with a large pelvic mass (large dimension of 20 cm). The tumor was removed, and the histopathology displayed spindle-predominant morphology with focal epithelioid areas, myxoid stromal tissue, and notable lymphoid infiltration with tertiary lymphoid structures. Ten mitoses were quantified in 50 high-power fields without nuclear pleomorphism. DOG1 showed strong and diffuse positivity, and CD117 showed moderate positivity. Succinate dehydrogenase subunit B (SDHB) was retained, Pan-TRK was focal positive (nuclear pattern), and the proliferation index Ki-67 was 7%. Next-generation sequencing (NGS) detected an ETV6::NTRK3 fusion, and this finding was confirmed by fluorescence in situ hybridization (FISH), which showed NTRK3 rearrangement. In addition, an RB1 mutation was found by NGS. The follow-up CT scan revealed peritoneal nodules suggestive of peritoneal dissemination, and Entrectinib (a TRK inhibitor) was administered. After 3 months of follow-up, a new CT scan showed a complete response. Based on our results and the cases from the literature, GISTs with NTRK fusions are very uncommon so far; hence, further screening studies, including more WT GIST cases, may increase the possibility of finding additional cases. The present case may offer new insights into the potential introduction of TRK inhibitors as treatments for GISTs with NTRK fusions. Additionally, the presence of abundant lymphoid infiltration in the present case may prompt further research into immunotherapy as a possible additional therapeutic option.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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ETV6::NTRK3 Fusion-Positive Wild-Type Gastrointestinal Stromal Tumor (GIST) with Abundant Lymphoid Infiltration (TILs and Tertiary Lymphoid Structures): A Report on a New Case with Therapeutic Implications and a Literature Review

Machado,

Claramunt-Alonso,

Lavernia

et al. 2024

IJMS

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“…The NTRK family consists of NTRK1 , NTRK2 , and NTRK3 genes encoding the tropomyosin receptor kinase (TRK) A, B, and C, respectively. Oncogenic TRK activation is mainly due to the fusion of NTRK genes and is involved in the pathogenesis of many tumors, including WT -GISTs [ 7 , 84 , 85 , 86 ]. GISTs with NTRK rearrangements occur less frequently in the stomach are frequently larger, and the epithelioid type has a higher risk of recurrence [ 87 ].…”

Section: Other Mutations In Gistsmentioning

confidence: 99%

Emerging Targeted Therapeutic Strategies to Overcome Imatinib Resistance of Gastrointestinal Stromal Tumors

Masucci

Motti

Minopoli

et al. 2023

IJMS

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Gastrointestinal stromal tumors (GISTs) are the most common malignant mesenchymal neoplasms of the gastrointestinal tract. The gold standard for the diagnosis of GISTs is morphologic analysis with an immunohistochemical evaluation plus genomic profiling to assess the mutational status of lesions. The majority of GISTs are driven by gain-of-function mutations in the proto-oncogene c-KIT encoding the tyrosine kinase receptor (TKR) known as KIT and in the platelet-derived growth factor-alpha receptor (PDGFRA) genes. Approved therapeutics are orally available as tyrosine kinase inhibitors (TKIs) targeting KIT and/or PDGFRA oncogenic activation. Among these, imatinib has changed the management of patients with unresectable or metastatic GISTs, improving their survival time and delaying disease progression. Nevertheless, the majority of patients with GISTs experience disease progression after 2–3 years of imatinib therapy due to the development of secondary KIT mutations. Today, based on the identification of new driving oncogenic mutations, targeted therapy and precision medicine are regarded as the new frontiers for GISTs. This article reviews the most important mutations in GISTs and highlights their importance in the current understanding and treatment options of GISTs, with an emphasis on the most recent clinical trials.

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“…14 Wild-type GISTs consist of a heterogeneous and uncommon group of diseases with alternative proliferative signals, such as mutations in succinate dehydrogenase (SDH), neuro-fibromatosis type 1 (NF1), BRAF, KRAS, NTRK, or FGFR. 15…”

Section: Endoscopic Submucosal Dissection (Esd) Is a Well-establishedmentioning

confidence: 99%

Endoscopic submucosal dissection for ultra‐low large rectal stromal tumor after preoperative imatinib therapy: A case report and review

Liu

Feng

2022

J of Digest Diseases

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Resected High-Risk Rectal GIST Harboring NTRK1 Fusion: a Case Report and Review of the Literature

Cited by 8 publications

References 13 publications

ETV6::NTRK3 Fusion-Positive Wild-Type Gastrointestinal Stromal Tumor (GIST) with Abundant Lymphoid Infiltration (TILs and Tertiary Lymphoid Structures): A Report on a New Case with Therapeutic Implications and a Literature Review

ETV6::NTRK3 Fusion-Positive Wild-Type Gastrointestinal Stromal Tumor (GIST) with Abundant Lymphoid Infiltration (TILs and Tertiary Lymphoid Structures): A Report on a New Case with Therapeutic Implications and a Literature Review

Emerging Targeted Therapeutic Strategies to Overcome Imatinib Resistance of Gastrointestinal Stromal Tumors

Endoscopic submucosal dissection for ultra‐low large rectal stromal tumor after preoperative imatinib therapy: A case report and review

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