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Variants & evidence
7,750 evidence items mapped to this entity or its descendants, grouped by molecular profile, then therapy. 50 items per page.
| Therapy | Cancer | Type | Level | Direction · significance | Rating (1–5) | Status | Evidence | Source |
|---|---|---|---|---|---|---|---|---|
| LYN Fusion3 | ||||||||
| (diagnostic) | B Lymphoblastic Leukemia/Lymphoma, BCR-ABL1-Like | Diagnostic | C | Supports Positive | 3 | accepted | EID12801In this 2017 study, the authors characterized 284 cases of Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) identified from a cohort of 1,389 pediatric patients with high-risk B… (full text at CIViC) PMID 28408464 · Reshmi et al., 2017 · Open in CIViC | civic |
| 〃 | B Lymphoblastic Leukemia/Lymphoma, BCR-ABL1-Like | Diagnostic | C | Supports Positive | 3 | accepted | EID12802This retrospective Japanese multicenter study investigated kinase-activating gene fusions in pediatric B-lymphoblastic leukemia (B-ALL) lacking recurrent cytogenetic abnormalities, with the goal of de… (full text at CIViC) PMID 27176795 · Imamura et al., 2016 · Open in CIViC | civic |
| 〃 | B Lymphoblastic Leukemia/Lymphoma, BCR-ABL1-Like | Diagnostic | C | Supports Positive | 3 | accepted | EID12809In this 2020 case report, the authors present a pediatric patient with relapsed B-lymphoblastic leukemia (B-ALL), providing critical evidence for the diagnostic and therapeutic role of LYN fusions. Th… (full text at CIViC) PMID 32266142 · Dai et al., 2020 · Open in CIViC | civic |
| MAML2 Fusion3 | ||||||||
| (diagnostic) | Salivary Gland Mucoepidermoid Carcinoma | Diagnostic | B | Supports Positive | 4 | accepted | EID11591In this 2010 study, the authors included 55 salivary gland mucoepidermoid carcinomas (MEC) and a control group of 36 potential MEC mimics, including Warthin tumors, oncocytomas, squamous cell carcinom… (full text at CIViC) PMID 20588178 · Seethala et al., 2010 · Open in CIViC | civic |
| 〃 | Salivary Gland Mucoepidermoid Carcinoma | Diagnostic | B | Supports Positive | 3 | accepted | EID11592In this 2013 study, the authors investigated 95 salivary gland mucoepidermoid carcinomas (MEC) using FFPE material. RT-PCR and FISH were utilized to detect CRTC1::MAML2 and CRTC3::MAML2 fusions, as we… (full text at CIViC) PMID 23035786 · Noda et al., 2013 · Open in CIViC | civic |
| 〃 | Salivary Gland Mucoepidermoid Carcinoma | Diagnostic | B | Supports | ||||
| MITF Fusion1 | ||||||||
| (diagnostic) | Renal Cell Carcinoma with MiT Translocations | Diagnostic | C | Supports Positive | 1 | accepted | EID11702Bakouny, et al. (2022) performed a comprehensive study of the molecular and clinical features of 90 translocation renal cell carcinomas (tRCCs), defined as subtype of kidney cancer driven by MiT/TFE g… (full text at CIViC) PMID 34986355 · Bakouny et al., 2022 · Open in CIViC | civic |
| NCOA2 Fusion5 | ||||||||
| (diagnostic) | Spindle Cell Rhabdomyosarcoma | Diagnostic | B | Supports Positive | 4 | accepted | EID12699In this 2025 retrospective study, 14 spindle cell rhabdomyosarcoma (SCRMS) cases previously identified as possessing ZFP64::NCOA2 or ZFP64::NCOA3 fusions were pulled from clinical archives to assess c… (full text at CIViC) PMID 41075874 · Dehner et al., 2025 · Open in CIViC | civic |
| 〃 | Spindle Cell Rhabdomyosarcoma | Diagnostic | B | Supports Positive | 3 | accepted | EID11566In this 2016 study, the authors analyzed 26 pediatric spindle and sclerosing rhabdomyosarcomas (SRMS) using FISH, targeted DNA, and whole transcriptome sequencing to define their molecular landscape. … (full text at CIViC) PMID 26501226 · Alaggio et al., 2016 · Open in CIViC | civic |
| (prognostic) | Spindle Cell Rhabdomyosarcoma | Prognostic | B | Supports Better Outcome | 3 | |||
| NR4A3 Fusion4 | ||||||||
| (diagnostic) | Acinar Cell CarcinomaALIAS | Diagnostic | B | Supports Positive | 4 | accepted | EID12816In this 2023 study, the authors evaluated the diagnostic utility of NR4A3 immunohistochemistry in acinic cell carcinoma (AciCC) of the salivary gland. The cohort included 128 AciCCs, comprising 85 cla… (full text at CIViC) PMID 36469101 · Klubíčková et al., 2023 · Open in CIViC | civic |
| 〃 | Acinar Cell CarcinomaALIAS | Diagnostic | B | Supports Positive | 4 | accepted | EID12828In this 2019 study, the authors aimed to evaluate the usefulness of NR4A3 immunostaining and compare it with NR4A3 Fluorescence in situ hybridization (FISH) for the differential diagnosis of acinic ce… (full text at CIViC) PMID 31094928 · Haller et al., 2019 · Open in CIViC | civic |
| 〃 | Acinar Cell CarcinomaALIAS | |||||||
| NRG1 Fusion4 | ||||||||
| Afatinib | Pancreatic Adenocarcinoma | Predictive | C | Supports Sensitivity Response | 4 | accepted | EID6273In patients with KRAS wild-type (KRASwt) tumors druggable gene fusions have been identified. These alterations included recurrent NRG1 rearrangements predicted to drive PDAC development through aberra… (full text at CIViC) PMID 29802158 · Heining et al., 2018 · Open in CIViC | civic |
| Erlotinib + PertuzumabCombination | Pancreatic Adenocarcinoma | Predictive | C | Supports Sensitivity Response | 3 | submitted | EID7534In patients with KRAS wild-type (KRASwt) tumors druggable gene fusions have been identified. These alterations included recurrent NRG1 rearrangements predicted to drive PDAC development through aberra… (full text at CIViC) PMID 29802158 · Heining et al., 2018 · Open in CIViC | civic |
| Zenocutuzumab-zbco | Lung Non-Small Cell CarcinomaCURATED_BROADER | |||||||
| NTRK1 Fusion11 | ||||||||
| Entrectinib | Solid NeoplasmCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 5 | accepted | EID11124Describes a meta-analysis of three separate phase I or II trials: ALKA-372-001, STARTRK-1, and STARTRK-2. All of these evaluate entrectinib in NTRK fusion-positive solid tumours. 31/54 had objective r… (full text at CIViC) PMID 31838007 · Doebele et al., 2020 · Open in CIViC | civic |
| 〃 | Solid NeoplasmCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 3 | accepted | EID2948The overall safety and antitumor activity of entrectinib was described for two phase I trials of patients with advanced solid tumors harboring NTRK1/2/3, ROS1, or ALK gene fusions. NTRK1 fusions were … (full text at CIViC) PMID 28183697 · Drilon et al., 2017 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | |||||||
| NTRK1 F589L + NTRK1 Fusion1 | ||||||||
| Larotrectinib | Solid NeoplasmCURATED_BROADER | Predictive | A | Supports Resistance | 2 | submitted | EID11542In this phase 1/2 study 55 patients from 4 months to 76 years old with TRK-fusion positive tumors were given NTRK inhibitor larotrectinib. Patients had 17 unique NTRK fusion types. Patient overall res… (full text at CIViC) PMID 29466156 · Drilon et al., 2018 · Open in CIViC | civic |
| NTRK1 G595R + NTRK1 Fusion1 | ||||||||
| Larotrectinib | Solid NeoplasmCURATED_BROADER | Predictive | A | Supports Resistance | 3 | submitted | EID11540In this phase 1/2 study 55 patients from 4 months to 76 years old with TRK-fusion positive tumors were given NTRK inhibitor larotrectinib. Patients had 17 unique NTRK fusion types. Patient overall res… (full text at CIViC) PMID 29466156 · Drilon et al., 2018 · Open in CIViC | civic |
| NTRK1 G667S + NTRK1 Fusion1 | ||||||||
| Larotrectinib | Solid NeoplasmCURATED_BROADER | Predictive | A | Supports Resistance | 2 | submitted | EID11543In this phase 1/2 study 55 patients from 4 months to 76 years old with TRK-fusion positive tumors were given NTRK inhibitor larotrectinib. Patients had 17 unique NTRK fusion types. Patient overall res… (full text at CIViC) PMID 29466156 · Drilon et al., 2018 · Open in CIViC | civic |
| NTRK1 Fusion + NTRK2 Fusion + NTRK3 FusionNTRK1NTRK3NTRK21 | ||||||||
| Entrectinib | Solid NeoplasmCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID12071In the STARTRK-NG (NCT02650401) phase 1/2 trial, 43 pediatric and young adult patients (age <22 years) with recurrent or refractory solid tumors, including primary CNS tumors, were evaluated for respo… (full text at CIViC) PMID 35395680 · Desai et al., 2022 · Open in CIViC | civic |
| NTRK2 Fusion3 | ||||||||
| (diagnostic) | Pilocytic Astrocytoma | Diagnostic | C | Supports Positive | 3 | submitted | EID7151Genetic alterations in pilocytic astrocytoma (PA) were evaluated. Two new NTRK2 fusion events were identified in this study. These two NTRK2 fusion events, namely QKI-NTRK2 (2 of 96 samples) and NACC2… (full text at CIViC) PMID 23817572 · Jones et al., 2013 · Open in CIViC | civic |
| Entrectinib | Solid NeoplasmCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 1 | accepted | EID1122254 patients aged 18 or older with metastatic or locally advanced NTRK-fusion positive solid tumours (including ten tumour types and 19 unique histologies) were enrolled in one of three phase 1 or 2 tr… (full text at CIViC) PMID 31838007 · Doebele et al., 2020 · Open in CIViC | civic |
| Larotrectinib | Solid NeoplasmCURATED_BROADER | Predictive | ||||||
| NTRK3 Fusion4 | ||||||||
| Entrectinib | Solid NeoplasmCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 5 | accepted | EID11125Describes a meta-analysis of three separate phase I or II trials: ALKA-372-001, STARTRK-1, and STARTRK-2. All of these evaluate entrectinib in NTRK fusion-positive solid tumours. 31/54 had objective r… (full text at CIViC) PMID 31838007 · Doebele et al., 2020 · Open in CIViC | civic |
| 〃 | Malignant NeoplasmALIAS | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID2949in two phase I studies in patients with advanced or metastatic solid tumors, including patients with active central nervous system (CNS) disease. Here, we summarize the overall safety and report the a… (full text at CIViC) PMID 28183697 · Drilon et al., 2017 · Open in CIViC | civic |
| Larotrectinib | Solid NeoplasmCURATED_BROADER | |||||||
| NTRK3 G623R + NTRK3 Fusion1 | ||||||||
| Larotrectinib | Solid NeoplasmCURATED_BROADER | Predictive | A | Supports Resistance | 3 | submitted | EID11541In this phase 1/2 study 55 patients from 4 months to 76 years old with TRK-fusion positive tumors were given NTRK inhibitor larotrectinib. Patients had 17 unique NTRK fusion types. Patient overall res… (full text at CIViC) PMID 29466156 · Drilon et al., 2018 · Open in CIViC | civic |
| NTRK3 G696A + NTRK3 Fusion1 | ||||||||
| Larotrectinib | Solid NeoplasmCURATED_BROADER | Predictive | A | Supports Resistance | 2 | submitted | EID11544In this phase 1/2 study 55 patients from 4 months to 76 years old with TRK-fusion positive tumors were given NTRK inhibitor larotrectinib. Patients had 17 unique NTRK fusion types. Patient overall res… (full text at CIViC) PMID 29466156 · Drilon et al., 2018 · Open in CIViC | civic |
| NUTM1 Fusion4 | ||||||||
| (diagnostic) | NUT CarcinomaALIAS | Diagnostic | B | Supports Positive | 4 | accepted | EID12050In this 2020 study, the authors included a total of 141 NUT carcinomas defined by rearrangement of NUTM1 detected by IHC, cytogenetics, FISH or sequencing. The median age at diagnosis was 24 years (ra… (full text at CIViC) PMID 32328562 · Chau et al., 2020 · Open in CIViC | civic |
| 〃 | NUT CarcinomaALIAS | Diagnostic | B | Supports Positive | 4 | accepted | EID12051In this 2004 study, the authors sought to identify carcinomas with translocation t(15;19)(q13, p13.1), which results in the novel oncogenic fusion BRD4::NUTM1 (described as NUT). The authors screened … (full text at CIViC) PMID 15483023 · French et al., 2004 · Open in CIViC | civic |
| 〃 | NUT CarcinomaALIAS | |||||||
| EGFR Fusion1 | ||||||||
| (oncogenic) | Malignant NeoplasmALIAS | Oncogenic | C | Supports Oncogenicity | 1 | submitted | EID12551Next generation sequencing was performed on 35023 Chinese cases with 13 different solid tumor types. EGFR Fusions were detected in 106 samples. All EGFR fusions contained the complete tyrosine kinase … (full text at CIViC) PMID 39054543 · Zhang et al., 2024 · Open in CIViC | civic |
| PDGFRA Fusion1 | ||||||||
| (diagnostic) | Chronic Myelomonocytic Leukemia | Diagnostic | A | Supports Negative | 5 | accepted | EID1425The 2016 World Health Organization guidelines for the classification of myeloid malignancies uses the detection of PCM1-JAK2 or rearrangements involving PDGFRA, PDGFRB, or FGFR1 as recommended exclusi… (full text at CIViC) PMID 27069254 · Arber et al., 2016 · Open in CIViC | civic |
Data updated 20 hours agoSource updated unknownsource: civic (CC0)
Evidence levels, directions and ratings are those assigned by CIViC curators. "Submitted" items have not completed curation review. This is not treatment guidance.
| 3 |
| accepted |
EID11593In this 2009 study, the authors investigated 101 mucoepidermoid carcinomas (MECs) and 89 non-MEC salivary gland tumors using RT-PCR to detect CRTC1::MAML2, CRTC2::MAML2, and CRTC3::MAML2 fusions. The … (full text at CIViC) PMID 19749740 · Nakayama et al., 2009 · Open in CIViC |
| civic |
| accepted |
EID11567This study looked at 26 spindle cell and sclerosing rhabdomyosarcomas. 11 were congenital/infantile type diagnosed at birth or within one year of age, 10 of which harbored recurrent fusions involving … (full text at CIViC) PMID 26501226 · Alaggio et al., 2016 · Open in CIViC |
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| (diagnostic) | Spindle Cell Rhabdomyosarcoma | Diagnostic | B | Supports Positive | 3 | accepted | EID12727In this 2022 study, the authors included 40 patients aged ≤12 months diagnosed with spindle cell rhabdomyosarcoma (SCRMS) enrolled in international trials and registries, of whom 39 presented with loc… (full text at CIViC) PMID 35452896 · Whittle et al., 2022 · Open in CIViC | civic |
| 〃 | Spindle Cell Rhabdomyosarcoma | Diagnostic | C | Supports Positive | 3 | accepted | EID12731In this 2013 study, the authors included 21 spindle cell and sclerosing rhabdomyosarcomas (RMS), and a control group of 4 embryonal RMS and 3 ectomesenchymomas. RNA sequencing and FISH were utilized t… (full text at CIViC) PMID 23463663 · Mosquera et al., 2013 · Open in CIViC | civic |
| Diagnostic |
| B |
| Supports Positive |
| 3 |
| accepted |
EID12336In this 2022 study the authors included 4 cases of sinonasal acinic cell carcinoma and 10 acinic cell carcinoma cases of the parotid gland. All four sinonasal patients were male, aged from 27 to 70 ye… (full text at CIViC) PMID 34873305 · Wang et al., 2022 · Open in CIViC |
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| 〃 | Acinar Cell CarcinomaALIAS | Diagnostic | C | Supports Positive | 3 | accepted | EID12337In this 2023 study the authors included 4 cases of acinic cell carcinoma of the salivary gland. The age of the patients ranged from 13 to 16 years, and included 2 males and 2 females. Immunohistochemi… (full text at CIViC) PMID 36169793 · Cole et al., 2023 · Open in CIViC | civic |
| Predictive |
| A |
| Supports Sensitivity Response |
| 4 |
| accepted |
EID12246On December 4, 2024, the Food and Drug Administration granted accelerated approval to zenocutuzumab-zbco (Bizengri, Merus N.V.) for adults with advanced, unresectable, or metastatic non-small cell lun… (full text at CIViC) PMID 39908431 · Schram et al., 2025 · Open in CIViC |
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| 〃 | Pancreatic Adenocarcinoma | Predictive | A | Supports Sensitivity Response | 4 | accepted | EID12247On December 4, 2024, the Food and Drug Administration granted accelerated approval to zenocutuzumab-zbco (Bizengri, Merus N.V.) for adults with advanced, unresectable, or metastatic non-small cell lun… (full text at CIViC) PMID 39908431 · Schram et al., 2025 · Open in CIViC | civic |
| Predictive |
| C |
| Supports Sensitivity Response |
| 3 |
| rejected |
EID29471378 cases of NSCLC were screened. One patient (frequency 0.1%) with a NTRK1 gene rearrangement (SQSTM1-NTRK1 Fusion) was treated with entrectinib in a phase 1 study. The patient had resolution of pri… (full text at CIViC) PMID 26565381 · Farago et al., 2015 · Open in CIViC |
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| Larotrectinib | Solid NeoplasmCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 4 | accepted | EID6567This was a Phase 1/2 study of 55 patients from 4 months to 76 years old with TRK-fusion positive tumors given NTRK inhibitor Larotrectinib. Patients had 17 unique NTRK fusion types. Patient overall re… (full text at CIViC) PMID 29466156 · Drilon et al., 2018 · Open in CIViC | civic |
| 〃 | Sarcoma | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID6569In a Phase 1/2 study involving 15 pediatric patients with infantile fibrosarcoma or soft tissue sarcoma, 8 patients had NTRK1 fusions. The patients were administered Larotrectinib, and 7 out of 8 pati… (full text at CIViC) PMID 29606586 · Laetsch et al., 2018 · Open in CIViC | civic |
| 〃 | Malignant Pancreatic Neoplasm | Predictive | C | Supports Sensitivity Response | 3 | submitted | EID7649A patient with pancreatic cancer harboring NTRK fusion was treated with larotrectinib. The best overall response was PR at 2 months but the tumor progressed after 6 months. PMID 31605106 · O'Reilly et al., 2019 · Open in CIViC | civic |
| 〃 | Malignant NeoplasmALIAS | Predictive | C | Supports Sensitivity Response | 2 | accepted | EID2953Results from a phase I study show that the TRK inhibitor LOXO-101 is well tolerated and effective, with patients whose tumors bear NTRK fusions responding well and durably to this targeted therapy. Th… (full text at CIViC) PMID 26603524 · 2016 · Open in CIViC | civic |
| 〃 | Sarcoma | Predictive | C | Supports Sensitivity Response | 2 | rejected | EID2956LOXO-101 is an orally administered inhibitor of the TRK kinase and is highly selective only for the TRK family of receptors. The tumor of a 41-year-old woman with soft-tissue sarcoma metastatic to the… (full text at CIViC) PMID 26216294 · Doebele et al., 2015 · Open in CIViC | civic |
| 〃 | Malignant Pancreatic Neoplasm | Predictive | C | Supports Sensitivity Response | 2 | submitted | EID6051In a Phase I/II study of Larotrectinib, highly selective TRK inhibitor, one patient with pancreatic cancer with NTRK fusion showed PR. PMID 29466156 · Drilon et al., 2018 · Open in CIViC | civic |
| 〃 | Cholangiocarcinoma | Predictive | C | Supports Sensitivity Response | 2 | submitted | EID6052In a Phase I/II study of Larotrectinib, highly selective TRK inhibitor, two patient with cholangiocarcinoma with NTRK fusion was enrolled. One of the two patient showed PR. PMID 29466156 · Drilon et al., 2018 · Open in CIViC | civic |
| Crizotinib + Larotrectinib + LestaurtinibSubstitutes | Lung Adenocarcinoma | Predictive | D | Supports Sensitivity Response | 3 | accepted | EID1019Two patients were found to harbor gene fusions maintaining the kinase domain of NTRK1 (3' partner), specifically: MPRIP-NTRK1 and CD74-NTRK1. Both of these fusions lead to constitutive kinase activit… (full text at CIViC) PMID 24162815 · Vaishnavi et al., 2013 · Open in CIViC | civic |
| Supports Sensitivity Response |
| 2 |
| accepted |
EID10392A pooled analysis of three phase 1/2 clinical trials investigating the efficacy and safety of larotrectinib in 159 NTRK fusion positive solid tumor patients (1 month - 84 years old) confirmed larotrec… (full text at CIViC) PMID 32105622 · Hong et al., 2020 · Open in CIViC |
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| Predictive |
| A |
| Supports Sensitivity Response |
| 4 |
| accepted |
EID6568This was a Phase 1/2 study of 55 patients from 4 months to 76 years old with TRK-fusion positive tumors given NTRK inhibitor Larotrectinib. Patients had 17 unique NTRK fusion types. Patient overall re… (full text at CIViC) PMID 29466156 · Drilon et al., 2018 · Open in CIViC |
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| 〃 | Malignant NeoplasmALIAS | Predictive | B | Supports Sensitivity Response | 2 | submitted | EID2954Results from a phase I study show that the TRK inhibitor LOXO-101 is well tolerated and effective, with patients whose tumors bear NTRK fusions responding well and durably to this targeted therapy. PMID 26603524 · 2016 · Open in CIViC | civic |
| C |
| Supports Positive |
| 2 |
| accepted |
EID12009RNA sequencing identified NUTM1 fusions in six patients with primary undifferentiated soft tissue and visceral tumors. Fusions included BRD4::NUTM1 (three cases), BRD3::NUTM1, MXD1::NUTM1, and BCORL1… (full text at CIViC) PMID 29356724 · Dickson et al., 2018 · Open in CIViC |
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| Molibresib | NUT CarcinomaALIAS | Predictive | B | Supports Sensitivity Response | 3 | submitted | EID12055NUT carcinoma is known to be driven by BET fusion proteins, including BRD4::NUTM1 and BRD3::NUTM1, raising the possibility of response to BET inhibitors. Of 19 patients with NUT carcinoma treated wit… (full text at CIViC) PMID 32328561 · Piha-Paul et al., 2020 · Open in CIViC | civic |