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BIOMARKER:

LMNA-NTRK1 fusion

i
Other names: LMNA, Prelamin-A/C, LMN1, Mandibuloacral dysplasia type A, Limb girdle muscular dystrophy 1B (autosomal dominant), Cardiomyopathy dilated 1A (autosomal dominant), Lamin A/C, FPLD2, LGMD1B, CMT2B1, Renal carcinoma antigen NY-REN-32, Progeria 1 (hutchinson-gilford type), NTRK1, MTC, TRK, TRKA, Neurotrophic tyrosine kinase, receptor, type 1
Entrez ID:
2ms
Translation into Clinical Practice of the G1-G7 Molecular Subgroup Classification of Glioblastoma: Comprehensive Demographic and Molecular Pathway Profiling. (PubMed, Cancers (Basel))
The correlations between the MAPK pathway G1-G7 subgroups and the PI3-kinase/PTEN, TERT, cell cycle G1 phase and p53 pathways defined characteristic subgroup pathway profiles amenable to personalized targeted therapy. This analysis validated the first all-inclusive molecular classification of glioblastoma, showed significant demographic and molecular differences between subgroups, and provided the first ethnic molecular comparison of glioblastoma.
Journal • Tumor mutational burden
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EGFR (Epidermal growth factor receptor) • TMB (Tumor Mutational Burden) • PTEN (Phosphatase and tensin homolog) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NF1 (Neurofibromin 1) • LMNA (Lamin A/C) • PTPRZ1 (Protein Tyrosine Phosphatase Receptor Type Z1)
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EGFR mutation • NTRK1 fusion • NF1 mutation • ROS1 fusion • GOPC-ROS1 fusion • LMNA-NTRK1 fusion • NTRK1 overexpression
4ms
Detection of Novel Tyrosine Kinase Fusion Genes as Potential Therapeutic Targets in Bone and Soft Tissue Sarcomas Using DNA/RNA-based Clinical Sequencing. (PubMed, Clin Orthop Relat Res)
DNA- and RNA-based screening systems may be useful for detecting tyrosine kinase fusion genes in specific fusion-negative sarcomas and identifying key therapeutic targets, leading to possible breakthroughs in the treatment of bone and soft tissue sarcomas. Given that current DNA sequencing misses fusion genes, RNA-based screening systems should be widely considered as a worldwide test for sarcoma. If standard treatments such as chemotherapy are not effective, or even if the sarcoma is of bone, RNA sequencing should be considered to identify as many therapeutic targets as possible.
Journal
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EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • RET (Ret Proto-Oncogene) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • KDR (Kinase insert domain receptor) • CDK4 (Cyclin-dependent kinase 4) • LMNA (Lamin A/C) • CLTC (Clathrin Heavy Chain) • NTRK (Neurotrophic receptor tyrosine kinase) • CEP290 (Centrosomal Protein 290) • FOXP2 (Forkhead Box P2)
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NTRK1 fusion • NTRK3 fusion • ALK fusion • LMNA-NTRK1 fusion • NTRK3 positive • NTRK positive • NTRK fusion
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TruSight Tumor 170 Assay
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Vitrakvi (larotrectinib)
6ms
The association between neurotrophic tropomycin receptor kinase (NTRK) variants of unknown significance (VUS’s) and response to immune checkpoint inhibitors in solid tumors (SITC 2023)
The statistical significance was limited to NTRK3 alterations but a trend for better mOS was evident in NTRK1 and NTRK2. Propsective validation and efforts to understand the underlying mechansims are warranted.
Checkpoint inhibition • IO biomarker
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NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • LMNA (Lamin A/C) • NTRK (Neurotrophic receptor tyrosine kinase)
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NTRK1 fusion • LMNA-NTRK1 fusion • NTRK fusion
6ms
Expanding the Spectrum of Fusion-driven Melanocytic Lesions: A Series of 4 Cases (ASDP 2023)
The spectrum of fusion-driven melanocytic lesions is rapidly expanding with the democratization of molecular testing. Tumors with CRTC1 :: TRIM11 are now known for their metastatic potential. Precise characterization of these entities may inform patient follow-up and management, including the opportunity for kinase inhibitor therapies.
Clinical • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
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TMB (Tumor Mutational Burden) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • LMNA (Lamin A/C) • WWP2 (WW Domain Containing E3 Ubiquitin Protein Ligase 2) • CRTC1 (CREB Regulated Transcription Coactivator 1)
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TMB-H • NTRK1 fusion • LMNA-NTRK1 fusion
7ms
A child with LMNA-NTRK1 rearranged spindle cell neoplasm (EADV 2023)
All the findings confirmed the diagnosis of LMNA-NTRK1 rearranged spindle cell neoplasm, a recently described and rare molecularly-defined soft tissue tumor that may have a wide spectrum of morphologies and histological grades, with frequent co-expression of CD34 and S100. Due to the highly infiltrative growth pattern, the tumor has a propensity for local recurrence, if incompletely excised, but none has been shown to metastasize. In our patient, there was no recurrence more than 3 years after the excision.
Clinical
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NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • CD34 (CD34 molecule) • LMNA (Lamin A/C) • NTRK (Neurotrophic receptor tyrosine kinase)
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NTRK1 fusion • LMNA-NTRK1 fusion
9ms
Evaluating Gene Fusions in Solid Tumors by Next- Generation Sequencing: A Tertiary Centre Experience (AMP Europe 2023)
"Gene fusions represent crucial targets in the context of precision medicine. NGS testing for fusion detection not only allows analysis of multiple targets but also saves time and material. The identification of novel fusions in this study also highlights the potential for future therapeutic targets."
BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • MSI (Microsatellite instability) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • FGFR3 (Fibroblast growth factor receptor 3) • FGFR1 (Fibroblast growth factor receptor 1) • TACC3 (Transforming acidic coiled-coil containing protein 3) • ETV6 (ETS Variant Transcription Factor 6) • LMNA (Lamin A/C) • DCTN1 (Dynactin Subunit 1) • AGK (Acylglycerol Kinase) • SDC4 (Syndecan 4) • NTRK (Neurotrophic receptor tyrosine kinase)
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EGFR mutation • NTRK1 fusion • MET exon 14 mutation • ROS1 positive • EGFRvIII mutation • FGFR1 fusion • FGFR3 fusion • LMNA-NTRK1 fusion • SDC4-ROS1 fusion • NTRK fusion
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SOPHiA DDM™ Solid Tumor Plus Solution
11ms
Elaboration of NTRK-rearranged colorectal cancer: Integration of immunoreactivity pattern, cytogenetic identity, and rearrangement variant. (PubMed, Dig Liver Dis)
Regarding break-apart FISH, NTRK detection is difficult because of the diversity of signal patterns. Further research is warranted to identify the characteristics of NTRK-fusion CRCs.
Journal
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NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • EML4 (EMAP Like 4) • ETV6 (ETS Variant Transcription Factor 6) • TPM3 (Tropomyosin 3) • LMNA (Lamin A/C) • NTRK (Neurotrophic receptor tyrosine kinase)
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MSI-H/dMMR • NTRK1 fusion • NTRK3 fusion • ETV6-NTRK3 fusion • TPM3-NTRK1 fusion • LMNA-NTRK1 fusion • NTRK1 positive • NTRK positive • NTRK fusion
over1year
Intestinal LMNA::NTRK1-fused spindle cell neoplasm with S100 and CD34 coexpression: a new case. (PubMed, BMJ Case Rep)
Here, we present a recently encountered intestinal spindle cell neoplasm harbouring an LMNA::NTRK1 gene fusion in a woman in her early 20s, which was initially thought to represent a GIST or a solitary fibrous tumour. Awareness of this emerging tumour type in the gastrointestinal tract is important due to treatment implications.
Journal
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BRAF (B-raf proto-oncogene) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • RAS (Rat Sarcoma Virus) • CD34 (CD34 molecule) • LMNA (Lamin A/C) • SOX10 (SRY-Box 10) • NTRK (Neurotrophic receptor tyrosine kinase)
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NTRK1 fusion • BRAF wild-type • RAS wild-type • LMNA-NTRK1 fusion • PDGFR wild-type
over1year
Pan-Solid Tumor Identification of NTRK Fusions Utilizing RNA Sequencing Identifies Diverse Fusion Partners (AMP 2022)
NTRK1, NTRK2, and NTRK3 fusions are clinically relevant driver alterations across solid tumor types. These fusions are difficult to detect, as the breakpoints occur across large intronic regions and they have many partner genes, with 10 novel fusion partners identified in this study. These data emphasize how important CGP with RNA sequencing is to identify all NTRK fusions for optimal patient treatment.
Tumor Mutational Burden • MSi-H Biomarker
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • LMNA (Lamin A/C) • KANK1 (KN Motif And Ankyrin Repeat Domains 1) • NTRK (Neurotrophic receptor tyrosine kinase) • PIAS4 (Protein Inhibitor Of Activated STAT 4) • PRKACA (Protein Kinase CAMP-Activated Catalytic Subunit Alpha)
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TMB-H • MSI-H/dMMR • KRAS G12C • HER-2 amplification • NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • ALK fusion • KRAS G13D • KRAS G12 • KRAS G13 • LMNA-NTRK1 fusion • NTRK fusion
over1year
Pan-tropomyosin receptor kinase immunohistochemistry is a feasible routine screening strategy for NTRK fusions in mismatch repair-deficient colorectal carcinomas. (PubMed, Hum Pathol)
Interestingly, pan-TRK positivity was observed in one case with precursor lesions in both precancerous and cancerous regions, whereas MLH1 loss was restricted to the cancerous region. In summary, an optimized multi-step algorithm using pan-TRK IHC as a screening method was proposed to identify CRC patients harboring NTRK fusions.
Journal • Mismatch repair
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NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • EML4 (EMAP Like 4) • ETV6 (ETS Variant Transcription Factor 6) • MLH1 (MutL homolog 1) • TPM3 (Tropomyosin 3) • LMNA (Lamin A/C) • NTRK (Neurotrophic receptor tyrosine kinase)
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MSI-H/dMMR • NTRK1 fusion • NTRK3 fusion • ETV6-NTRK3 fusion • TPM3-NTRK1 fusion • LMNA-NTRK1 fusion • NTRK fusion
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VENTANA pan-TRK (EPR17341) Assay
2years
Gene fusions and oncogenic mutations in MLH1 deficient and BRAFV600E wild-type colorectal cancers. (PubMed, Virchows Arch)
"Our results show that kinase fusions (20/30, 67%) and most importantly targetable NTRK1 fusions (7/30, 23%) are frequent in CRCs with dMLH1/BRAFV600Ewt/MLH1ph/RASwt. NGS was the most comprehensive method in finding the fusions, of which a subset can be screened by Idylla or IHC, provided that the result is confirmed by NGS."
Journal
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BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • RET (Ret Proto-Oncogene) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • MLH1 (MutL homolog 1) • TPM3 (Tropomyosin 3) • LMNA (Lamin A/C)
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BRAF V600E • BRAF V600 • NTRK1 fusion • RET fusion • ALK rearrangement • BRAF wild-type • ALK fusion • BRAF fusion • MLH1 mutation • TPM3-NTRK1 fusion • LMNA-NTRK1 fusion • NTRK expression
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Idylla™ GeneFusion Assay • Archer® FusionPlex® Lung Kit • VENTANA pan-TRK (EPR17341) Assay
2years
Primary NTRK-rearranged Spindle Cell Neoplasm of the Lung: A Clinicopathologic and Molecular Analysis of 3 Cases. (PubMed, Am J Surg Pathol)
All 3 patients are alive without the disease (median follow-up, 9 mo; range, 4 to 87 mo). The cases present herein demonstrate that NTRK-rearranged spindle cell neoplasms may occur primarily in the lung, albeit extremely rare, and should be included in the differential diagnosis of primary pulmonary spindle cell neoplasms.
Journal
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ALK (Anaplastic lymphoma kinase) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • TPM3 (Tropomyosin 3) • CD34 (CD34 molecule) • LMNA (Lamin A/C) • SOX10 (SRY-Box 10) • NTRK (Neurotrophic receptor tyrosine kinase) • STAT6 (Signal transducer and activator of transcription 6)
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NTRK1 fusion • TPM3-NTRK1 fusion • LMNA-NTRK1 fusion
over2years
Clinicopathologic Spectrum of NTRK fusion-positive Tumors Detected by Clinical RNA Sequencing Panel (USCAP 2022)
NTRK fusion-positive entities presented with a wide clinical and histologic spectrum, in a third of which the finding was unexpected. Uncommon/novel NTRK fusions may be present in classic entities negative for canonical fusions by targeted testing and comprehensive fusion detection should be pursued in such cases. Positivity for pan-TRK IHC, diffuse or focal, may be helpful in uncommon clinical presentations.
Clinical
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NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • ETV6 (ETS Variant Transcription Factor 6) • TPM3 (Tropomyosin 3) • LMNA (Lamin A/C) • KANK1 (KN Motif And Ankyrin Repeat Domains 1) • NTRK (Neurotrophic receptor tyrosine kinase)
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NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • ETV6-NTRK3 fusion • TPM3-NTRK1 fusion • LMNA-NTRK1 fusion • NTRK positive • NTRK fusion
over2years
[VIRTUAL] CANTRK: A Canadian Ring Study to Optimize Detection of NTRK Gene Fusions by Next-Generation Sequencing (NGS) (AMP 2021)
The CANTRK study demonstrated a high level of agreement in detection of NTRK fusions by NGS RNA testing across different NGS panels. Fusions not detected by certain panels were due either to absence of targets in amplicon primer panels, or potential bioinformatic challenges. Issues encountered during the study, such as defining quality criteria for reporting a positive result, types of results requiring confirmation, and reporting requirements, will be used to formulate a best practice guideline for analysis and reporting of gene fusions detected by NGS methods.
Next-generation sequencing
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ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • ETV6 (ETS Variant Transcription Factor 6) • TPM3 (Tropomyosin 3) • LMNA (Lamin A/C) • NTRK (Neurotrophic receptor tyrosine kinase)
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NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • ALK fusion • ETV6-NTRK3 fusion • ROS1 fusion • TPM3-NTRK1 fusion • LMNA-NTRK1 fusion • ALK-ROS1 fusion • NTRK fusion
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Oncomine™ Comprehensive Assay v3M • Archer® FusionPlex® Lung Kit • Oncomine Focus Assay • Oncomine Precision Assay
over2years
PBI-200: in vivo efficacy of a novel, highly CNS-penetrant next generation TRK inhibitor (SNO 2021)
A BaF3 xenograft model encoding the LMNA-NTRK1 gene fusion and G595R solvent front mutation showed superior efficacy with PBI-200 relative to first-generation compounds larotrectinib and entrectinib, and equivalent efficacy to the second-generation compound selitrectinib, in terms of tumor growth inhibition. Together, these data suggest that PBI-200 has potential as a best-in-class, highly CNS-penetrant next generation TRKi. A Phase 1/2 clinical trial evaluating PBI-200 in NTRK fusion-positive patients, including patients with PBT, is ongoing (NCT04901806).
Preclinical
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NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • LMNA (Lamin A/C) • NTRK (Neurotrophic receptor tyrosine kinase)
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NTRK1 fusion • LMNA-NTRK1 fusion • NTRK positive • NTRK1 G595R • NTRK fusion
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Vitrakvi (larotrectinib) • Rozlytrek (entrectinib) • selitrectinib (BAY 2731954) • PBI-200
over2years
NTRK oncogenic fusions are exclusively associated with the serrated neoplasia pathway in the colorectum and begin to occur in sessile serrated lesions. (PubMed, J Pathol)
NTRK fusions were detected only in SSLs of patients aged ?50?years, whereas BRAF mutation was found in younger age-onset SSLs. In conclusion, NTRK-rearranged colorectal tumors develop exclusively through the serrated neoplasia pathway and can be initiated from non-dysplastic SSLs without BRAF/KRAS mutations prior to full occurrence of MSI-high/CIMP-high.
Journal • MSi-H Biomarker
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KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • MSI (Microsatellite instability) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • EML4 (EMAP Like 4) • ETV6 (ETS Variant Transcription Factor 6) • MLH1 (MutL homolog 1) • TPM3 (Tropomyosin 3) • LMNA (Lamin A/C) • NTRK (Neurotrophic receptor tyrosine kinase)
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MSI-H/dMMR • BRAF mutation • NTRK1 fusion • NTRK3 fusion • TPM3-NTRK1 fusion • LMNA-NTRK1 fusion • NTRK fusion
over2years
[VIRTUAL] NTRK gene fusions in MLH1 deficient and BRAFV600E wild-type colorectal cancers (ECP 2021)
"Our study shows that Pan-Trk IHC detects NTRK1 fusions with 100% specificity in CRC. Our results confirm that NTRK1 fusions are frequently detected in dMLH1/BRAFV600Ewt (11%) and especially in dMLH1/MLH1ph/BRAFV600Ewt (16%) CRCs justifying screening for NTRK fusions in these subsets of CRCs. Our findings of NTRK1 fusions with partners LMNA, PLEKHA6 and TPM3 in CRC are consis- tent with previous studies but noteworthy, we introduce a novel IRF2BP2-NTRK1 fusion in CRC."
NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • MLH1 (MutL homolog 1) • TPM3 (Tropomyosin 3) • LMNA (Lamin A/C) • NTRK (Neurotrophic receptor tyrosine kinase)
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BRAF V600E • BRAF V600 • NTRK1 fusion • TPM3-NTRK1 fusion • LMNA-NTRK1 fusion • NTRK fusion
|
Archer® FusionPlex® Comprehensive Thyroid & Lung (CTL) Kit • VENTANA pan-TRK (EPR17341) Assay
over2years
[VIRTUAL] Genomic Testing Approaches Used to Identify Neurotrophic Tyrosine Receptor Kinase (NTRK) Gene Fusions for Patient Enrollment in Clinical Trials of Larotrectinib (ECP 2021)
NTRK gene fusions occur with many partners with the majority occurring at a low frequency across multiple tumour types, supporting the need for validated and appropriate testing methodologies that work agnostic of 5’ partners.
Clinical
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NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • ETV6 (ETS Variant Transcription Factor 6) • TPM3 (Tropomyosin 3) • LMNA (Lamin A/C) • NTRK (Neurotrophic receptor tyrosine kinase)
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NTRK1 fusion • NTRK3 fusion • ETV6-NTRK3 fusion • TPM3-NTRK1 fusion • LMNA-NTRK1 fusion • NTRK fusion
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Vitrakvi (larotrectinib)
3years
NTRK fusion-positive colorectal cancer in Japanese population. (PubMed, Pathol Int)
Both NTRK1 fusion-positive cases lacked activating mutations in KRAS and BRAF and were mismatch repair-deficient with loss of MLH1 and PMS2 expression and MLH1 promoter methylation. Our results show that receptor tyrosine kinase fusions are rare but present in colorectal cancers in Japanese patients, with a prevalence similar to that reported in other countries.
Clinical • Journal
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KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • MLH1 (MutL homolog 1) • PMS2 (PMS1 protein homolog 2) • TPM3 (Tropomyosin 3) • LMNA (Lamin A/C) • NTRK (Neurotrophic receptor tyrosine kinase)
|
KRAS mutation • MSI-H/dMMR • BRAF mutation • NTRK1 fusion • ALK positive • ROS1 fusion • ROS1 positive • TPM3-NTRK1 fusion • PMS2 mutation • LMNA-NTRK1 fusion • NTRK1 positive • NTRK positive • NTRK fusion
3years
Enrichment of Kinase Fusions in ESR1 Wild Type, Metastatic Breast Cancer Revealed by a Systematic Analysis of 4,854 Patients. (PubMed, Ann Oncol)
Kinase fusions in breast cancers are extremely rare, and appear to be enriched in hormone-resistant, metastatic carcinomas and mutually exclusive with ESR1 mutations. The present study expands the spectrum of genetic alterations activating MAPK signaling that can substitute for ESR1 mutations in this setting. Molecular testing at progression after endocrine therapy should include fusion testing, particularly in the absence of ESR1 hotspot alterations, in an effort to identify additional therapeutic options which may provide substantial clinical benefit.
Clinical • Journal
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HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • ER (Estrogen receptor) • ALK (Anaplastic lymphoma kinase) • FGFR2 (Fibroblast growth factor receptor 2) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • FGFR3 (Fibroblast growth factor receptor 3) • FGFR1 (Fibroblast growth factor receptor 1) • LMNA (Lamin A/C)
|
NTRK1 fusion • FGFR2 fusion • ER mutation • FGFR fusion • FGFR1 fusion • FGFR3 fusion • LMNA-NTRK1 fusion
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Vitrakvi (larotrectinib)
over3years
[VIRTUAL] Use of pan-TRK immunohistochemistry for identification of NTRK fusions in mesenchymal neoplasms – real life experience (ECP 2020)
Pan-TRK (clone EPR17341, Roche/Ventana) immunhistochemistry is a reliable, highly sensitive but less specific diagnostic marker that can be expressed in non-NTRK-rearranged mesenchymal neoplasms. Conclusion Pan-TRK (clone EPR17341, Roche/Ventana) can be used as a surrogate marker for an identification of NTRK fusion, nevertheless, an RNA-based NGS for detection of the specific fusion should be performed to confirm the rearrangement if patients are undergoing targeted therapy.
Clinical
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NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • ETV6 (ETS Variant Transcription Factor 6) • LMNA (Lamin A/C) • NTRK (Neurotrophic receptor tyrosine kinase)
|
NTRK1 fusion • LMNA-NTRK1 fusion • NTRK expression • NTRK fusion
|
VENTANA pan-TRK (EPR17341) Assay
over3years
[VIRTUAL] Use of pan-TRK immunohistochemistry for identification of NTRK fusions in mesenchymal neoplasms – real life experience (ECP 2020)
Pan-TRK (clone EPR17341, Roche/Ventana) immunhistochemistry is a reliable, highly sensitive but less specific diagnostic marker that can be expressed in non-NTRK-rearranged mesenchymal neoplasms. Conclusion Pan-TRK (clone EPR17341, Roche/Ventana) can be used as a surrogate marker for an identification of NTRK fusion, nevertheless, an RNA-based NGS for detection of the specific fusion should be performed to confirm the rearrangement if patients are undergoing targeted therapy.
Clinical
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NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • ETV6 (ETS Variant Transcription Factor 6) • LMNA (Lamin A/C) • NTRK (Neurotrophic receptor tyrosine kinase)
|
NTRK1 fusion • LMNA-NTRK1 fusion • NTRK expression • NTRK fusion
|
VENTANA pan-TRK (EPR17341) Assay
over3years
[VIRTUAL] Use of pan-TRK immunohistochemistry for identification of NTRK fusions in mesenchymal neoplasms – real life experience (ECP 2020)
Pan-TRK (clone EPR17341, Roche/Ventana) immunhistochemistry is a reliable, highly sensitive but less specific diagnostic marker that can be expressed in non-NTRK-rearranged mesenchymal neoplasms. Conclusion Pan-TRK (clone EPR17341, Roche/Ventana) can be used as a surrogate marker for an identification of NTRK fusion, nevertheless, an RNA-based NGS for detection of the specific fusion should be performed to confirm the rearrangement if patients are undergoing targeted therapy.
Clinical
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NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • ETV6 (ETS Variant Transcription Factor 6) • LMNA (Lamin A/C) • NTRK (Neurotrophic receptor tyrosine kinase)
|
NTRK1 fusion • LMNA-NTRK1 fusion • NTRK expression • NTRK fusion
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VENTANA pan-TRK (EPR17341) Assay
over3years
[VIRTUAL] Rare Case of Lipofibromatosis-Like Neural Tumor in a 50-Year-Old Man (CAP 2020)
Histologic examination revealed a spindle cell neoplasm with fascicular proliferation of relatively plump, bland, fibroblastic to somewhat neural-appearing cells growing in an infiltrative fashion through the preexisting connective tissue (Figure 212, B and C). Immunohistochemistry showed coexpression of S100 protein, CD34, and TRK, and the lesion was found to be positive for the LMNA-NTRK1 fusion by next-generation sequencing.
Clinical
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NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • CD34 (CD34 molecule) • LMNA (Lamin A/C)
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NTRK1 fusion • LMNA-NTRK1 fusion
over3years
Clinicopathological findings of pediatric NTRK fusion mesenchymal tumors. (PubMed, Diagn Pathol)
All cases of NTRK1 and NTRK3 fusion-positive pediatric tumors robustly expressed the Trk protein. A Trk immunopositive pattern and CD34/S100/nestin/CD10/SMA immunohistochemical expression may suggest the presence of NTRK fusion partner genes. LMNA-NTRK1 fusion sarcoma might be a low-grade subtype of infantile fibrosarcoma. Interestingly, more than half of the infantile fibrosarcoma cases were positive for S100 protein and CD10. The follow-up period of TPR-NTRK1 and LMNA-NTRK1 fusion-positive tumors are not enough to predict prognosis. However, ETV6-NTRK3 fusion-positive infantile fibrosarcomas showed an excellent prognosis with no evidence of disease for an average of 11.7 years, after gross total resection of the tumor.
Clinical • Journal
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NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • ETV6 (ETS Variant Transcription Factor 6) • CD34 (CD34 molecule) • LMNA (Lamin A/C) • NTRK (Neurotrophic receptor tyrosine kinase)
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NTRK1 fusion • NTRK3 fusion • ETV6-NTRK3 fusion • LMNA-NTRK1 fusion • NTRK1 positive • NTRK3 positive • NTRK positive • TPR-NTRK1 fusion • NTRK expression • NTRK fusion
over3years
Broadening the spectrum of NTRK rearranged mesenchymal tumors and usefulness of pan-TRK immunohistochemistry for identification of NTRK fusions. (PubMed, Mod Pathol)
"It can be used as a surrogate marker for identification of NTRK fusion, nevertheless, an RNA-based NGS for detection of the specific fusion should be performed to confirm the rearrangement, if patients are undergoing targeted therapy. Additionally, we identified NTRK-fusion-positive, primary mesenchymal tumors of the lung and the skin."
Journal
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NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • ETV6 (ETS Variant Transcription Factor 6) • LMNA (Lamin A/C) • NTRK (Neurotrophic receptor tyrosine kinase)
|
NTRK1 fusion • NTRK2 fusion • LMNA-NTRK1 fusion • NTRK positive • NTRK expression • NTRK fusion
|
VENTANA pan-TRK (EPR17341) Assay
over3years
[VIRTUAL] Neurotrophin tyrosine receptor kinase (NTRK) partners identified by next-generation sequencing in Chinese patients with solid tumours (ESMO 2020)
More than 20 different fusion partner genes of NTRK have been reported and most of these NTRK fusions respond well to NTRK inhibitors larotrectinib and/or entrectinib. Legal entity responsible for the study: The authors. Funding: Has not received any funding.
Clinical • Next-generation sequencing
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NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • CD74 (CD74 Molecule) • ETV6 (ETS Variant Transcription Factor 6) • LMNA (Lamin A/C) • NTRK (Neurotrophic receptor tyrosine kinase)
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NTRK1 fusion • LMNA-NTRK1 fusion • NTRK fusion
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Vitrakvi (larotrectinib) • Rozlytrek (entrectinib)
almost4years
[VIRTUAL] Large-scale study of NTRK fusions in Chinese solid tumors and using next generation sequencing: A multicenter study (AACR-II 2020)
TRK inhibitors such as LOXO-101, entrectinib, X396, AB-106, TL118 had remarkable and durable antitumor activities in patients (pts) with TRK fusion-positive cancers, regardless of age or tumor type. NTRK fusions are a rare molecular subtype in Chinese solid tumors. The NTRK gene fusions more commonly occurred in NSCLC (0.3%), CRC (0.4%) and BC (0.2%), and may occur without other targetable alterations such as EGFR, ALK, ROS1. The clinical evidence for responsiveness of NTRK fusions driven solid tumors provides an opportunity to personalize treatments and improve clinical outcomes for patients (pts).
Clinical • Next-generation sequencing
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EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • ETV6 (ETS Variant Transcription Factor 6) • TPM3 (Tropomyosin 3) • LMNA (Lamin A/C) • SQSTM1 (Sequestosome 1) • ESRP1 (Epithelial Splicing Regulatory Protein 1) • NTRK (Neurotrophic receptor tyrosine kinase)
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NTRK1 fusion • NTRK2 fusion • ETV6-NTRK3 fusion • TPM3-NTRK1 fusion • LMNA-NTRK1 fusion • NTRK fusion
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Vitrakvi (larotrectinib) • Rozlytrek (entrectinib) • Ensacove (ensartinib) • taletrectinib (AB-106) • Hamsa-1 (TL-118)