Rearrangements of NTRK1 gene in papillary thyroid carcinoma

Greco, Angela; Miranda, Claudia; Pierotti, Marco A.

doi:10.1016/j.mce.2009.10.009

Cited by 172 publications

(123 citation statements)

References 56 publications

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“…Finally, the RABGAP1L-NTRK1 fusion detected in case 2 of this series has not been reported previously (based on database searches of PubMed and COSMIC in January 2013), and NTRK1 alterations have not been analyzed or studied in cholangiocarcinoma. NTRK1 has been recently considered as a potential target for neuroblastoma and metastatic thyroid cancer [20,21]. Of potential interest is the recent report of a non-small cell lung cancer patient whose tumor featured an MPRIP-NTRK1 fusion and who responded to the kinase inhibitor crizotinib [22].…”

Section: Discussionmentioning

confidence: 99%

New Routes to Targeted Therapy of Intrahepatic Cholangiocarcinomas Revealed by Next-Generation Sequencing

Wang²,

et al. 2014

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Background. Intrahepatic cholangiocarcinoma (ICC) is a subtype of primary liver cancer that is rarely curable by surgery and is rapidly increasing in incidence. Relapsed ICC has a poor prognosis, and current systemic nontargeted therapies are commonly extrapolated from those used in other gastrointestinal malignancies. We hypothesized that genomic profiling of clinical ICC samples would identify genomic alterations that are linked to targeted therapies and that could facilitate a personalized approach to therapy. Methods. DNA sequencing of hybridization-captured libraries was performed for 3,320 exons of 182 cancer-related genes and 36 introns of 14 genes frequently rearranged in cancer. Sample DNA was isolated from 40 mm of 28 formalin-fixed paraffin-embedded ICC specimens and sequenced to high coverage.

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Section: Discussionmentioning

confidence: 99%

New Routes to Targeted Therapy of Intrahepatic Cholangiocarcinomas Revealed by Next-Generation Sequencing

Wang²,

et al. 2014

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“…Whereas the physiologic role of TRKA is relatively well elucidated (4), its involvement in neoplastic transformation and tumor progression was until very recently limited to identification of rearrangements in papillary thyroid carcinoma (PTC), a tumor type characterized by a relatively good prognosis and reports of activation due to presence of putative autocrine loops in neuroblastoma, prostate, pancreatic, and breast cancer (5)(6)(7)(8)(9)(10). However, chromosomal rearrangements involving the NTRK1 gene, resulting in the expression of different TRKA fusion proteins were recently reported by Vaishnavi and colleagues (11) in NSCLC, along with robust preclinical demonstration of the oncogenic potential of the predicted chimeric proteins.…”

Section: Introductionmentioning

confidence: 99%

Entrectinib, a Pan–TRK, ROS1, and ALK Inhibitor with Activity in Multiple Molecularly Defined Cancer Indications

Ardini

Menichincheri

Banfi

et al. 2016

Molecular Cancer Therapeutics

248

191

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Activated ALK and ROS1 tyrosine kinases, resulting from chromosomal rearrangements, occur in a subset of non-small cell lung cancers (NSCLC) as well as other tumor types and their oncogenic relevance as actionable targets has been demonstrated by the efficacy of selective kinase inhibitors such as crizotinib, ceritinib, and alectinib. More recently, low-frequency rearrangements of TRK kinases have been described in NSCLC, colorectal carcinoma, glioblastoma, and Spitzoid melanoma. Entrectinib, whose discovery and preclinical characterization are reported herein, is a novel, potent inhibitor of ALK, ROS1, and, importantly, of TRK family kinases, which shows promise for therapy of tumors bearing oncogenic forms of these proteins. Proliferation profiling against over 200 human tumor cell lines revealed that entrectinib is exquisitely potent in vitro against lines that are dependent on the drug's pharmacologic targets. Oral administration of entrectinib to tumor-bearing mice induced regression in relevant human xenograft tumors, including the TRKA-dependent colorectal carcinoma KM12, ROS1-driven tumors, and several ALK-dependent models of different tissue origins, including a model of brain-localized lung cancer metastasis. Entrectinib is currently showing great promise in phase I/II clinical trials, including the first documented objective responses to a TRK inhibitor in colorectal carcinoma and in NSCLC. The drug is, thus, potentially suited to the therapy of several molecularly defined cancer settings, especially that of TRK-dependent tumors, for which no approved drugs are currently available.

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“…Subsequently, NTRK1 fusions have been detected at a frequency of 12% in papillary thyroid cancers, with TPM3-NTRK1 being the most common gene rearrangement [9][10][11]. In addition, TRKC and very recently TRKB have also been shown to form oncogenic chimeras in multiple tumor types [12,13].…”

Section: Introductionmentioning

confidence: 99%

NTRK gene amplification in patients with metastatic cancer

et al. 2017

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Purpose: Neurotropic tropomyosin receptor kinase (NTRK) fusions have been identified in a variety of cancers, and tyrosine kinase inhibitors targeting the tropomyosin receptor kinase (TRK) receptor are currently in clinical trials. However, no reports are available on the effects of NTRK gene amplification. Methods: Samples from patients enrolled in the sequencing program were analyzed using a next-generation sequencing (NGS) cancer panel. For cases in which NTRK amplification (defined as ≥ 4.0 copies) was identified, panTRK immunohistochemical (IHC) staining of tissue microarrays was performed. Results: A total of 1,250 tumor specimens collected between February 2014 and January 2016 were analyzed using the NGS cancer panel. NTRK amplification was detected in 28 cases of various types of cancer. Among 27 cases, only four were positive for pan-TRK IHC. These four cases were melanoma, sarcoma, lung cancer, and gastric cancer. We found that 2.2% of cancer patients showed NTRK amplification using NGS cancer panel and NTRK amplification resulted in protein overexpression in 14.8% of these patients. Conclusion: Patients with NTRK amplification and increased TRK protein expression may be considered for inclusion in clinical trials for NTRK inhibitors.

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Rearrangements of NTRK1 gene in papillary thyroid carcinoma

Cited by 172 publications

References 56 publications

New Routes to Targeted Therapy of Intrahepatic Cholangiocarcinomas Revealed by Next-Generation Sequencing

New Routes to Targeted Therapy of Intrahepatic Cholangiocarcinomas Revealed by Next-Generation Sequencing

Entrectinib, a Pan–TRK, ROS1, and ALK Inhibitor with Activity in Multiple Molecularly Defined Cancer Indications

NTRK gene amplification in patients with metastatic cancer

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