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Variants & evidence
5,621 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 |
|---|---|---|---|---|---|---|---|---|
| PDGFRB Fusion4 | ||||||||
| (diagnostic) | Hematopoietic and Lymphoid Cell NeoplasmALIAS | Diagnostic | A | Supports Positive | 5 | accepted | EID1434The 2016 World Health Organization guidelines for the classification of myeloid malignancies and acute leukemia describes a new class of disease defined by myeloid or lymphoid neoplasms associated wit… (full text at CIViC) PMID 27069254 · Arber et al., 2016 · Open in CIViC | civic |
| 〃 | B Lymphoblastic Leukemia/Lymphoma, BCR-ABL1-Like | Diagnostic | A | Supports Positive | 4 | submitted | EID7022This study showed that, when detected in the context of B-cell lymphoblastic leukemia/lymphoma (B-ALL), PDGFRB fusions with different partner genes are associated with Ph-like molecular subtype of B-A… (full text at CIViC) PMID 25207766 · Roberts et al., 2014 · Open in CIViC | civic |
| Imatinib | Myeloproliferative NeoplasmCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 4 | accepted | EID1498Twelve patients with BCR-ABL-negative chronic myeloproliferative disease and reciprocal translocations involving PDGFRB received imatinib for a median of 47 months (range, 0.1-60 months). Eleven had p… (full text at CIViC) PMID 16960151 · David et al., 2007 · Open in CIViC | civic |
| 〃 | Myeloproliferative NeoplasmCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 4 | submitted | EID11272In this phase II, open-label, single-arm trial, 106 patients with 40 different malignancies were enrolled (78.5% solid tumours, 21.5% hematologic malignancies), including seven with myeloproliferative… (full text at CIViC) PMID 18451237 · Heinrich et al., 2008 · Open in CIViC | civic |
| NTRK3 e4::e11 | ||||||||
| (oncogenic) | Osteosarcoma | Oncogenic | C | Does Not Support Oncogenicity | 3 | accepted | EID11698Using next-generation DNA and RNA sequencing, three cases harboring NTRK fusions were identified in a cohort of 113 osteosarcomas (including primary tumors and metastases). Each of the three cases had… (full text at CIViC) PMID 32022484 · Ameline et al., 2020 · Open in CIViC | civic |
| RET Fusion10 | ||||||||
| Alectinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID4850Alectinib is an anaplastic lymphoma kinase tyrosine kinase inhibitor (TKI) that also has anti-RET activity in vitro. 4 patients with metastatic RET-rearranged NSCLC were identified. 3 of 4 had receive… (full text at CIViC) PMID 27544060 · Lin et al., 2016 · Open in CIViC | civic |
| Cabozantinib | Lung Adenocarcinoma | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID4847RET rearrangements are found in 1-2% of non-small-cell lung cancers. Cabozantinib is a multikinase inhibitor with activity against RET that produced a 10% overall response in unselected patients with … (full text at CIViC) PMID 27825636 · Drilon et al., 2016 · Open in CIViC | civic |
| Pralsetinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | ||||||
| ROS1 Fusion13 | ||||||||
| Ceritinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | submitted | EID11334In this phase II trial, 404 patients with advanced NSCLC underwent ROS1 pre-screening, and 32 patients with ROS1 rearrangement confirmed with FISH were enrolled. All patients except two were crizotini… (full text at CIViC) PMID 28520527 · Lim et al., 2017 · Open in CIViC | civic |
| Crizotinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 5 | accepted | EID7282In the ongoing phase 1 study PROFILE 1001, NSCLC patients with ROS1 rearrangement confirmed by FISH or RT-PCR received crizotinib 250mg twice daily. Among 53 patients, the ORR was 72% (95% CI, 58% to … (full text at CIViC) PMID 30980071 · Shaw et al., 2019 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell Carcinoma | |||||||
| TFCP2 Fusion2 | ||||||||
| (diagnostic) | Spindle Cell Rhabdomyosarcoma | Diagnostic | B | Supports Positive | 3 | accepted | EID12335In this study, the authors investigated the diagnostic role of TFCP2 fusions in spindle cell/sclerosing rhabdomyosarcoma (SC/S-RMS), a rare and aggressive subtype of rhabdomyosarcoma. While SC/S-RMS e… (full text at CIViC) PMID 31383960 · Le Loarer et al., 2020 · Open in CIViC | civic |
| 〃 | Spindle Cell Rhabdomyosarcoma | Diagnostic | C | Supports Positive | 4 | accepted | EID12325This study investigated the role of TFCP2-related gene fusions in primary intraosseous rhabdomyosarcomas (PIOS), particularly within spindle cell and sclerosing rhabdomyosarcoma subtypes. The analysis… (full text at CIViC) PMID 30720533 · Agaram et al., 2019 · Open in CIViC | civic |
| TFE3 Fusion6 | ||||||||
| (diagnostic) | Renal Cell Carcinoma with MiT Translocations | Diagnostic | B | Supports Positive | 4 | accepted | EID10150This study screened 983 Renal Cell Carcinoma (RCC) cases and identified 65 tumors with morphologic features suspicious of RCC with Xp11.2 translocation/TFE3 gene fusion (Xp11.2 RCC). TFE3 immunohistoc… (full text at CIViC) PMID 26169997 · He et al., 2015 · Open in CIViC | civic |
| 〃 | TFE3-Rearranged Renal Cell Carcinoma | Diagnostic | B | Supports Positive | 4 | accepted | EID11533Argani. et al,. (2016) included a total of 60 cases with known TFE3 gene rearrangements in this study of Xp11 translocation positive neoplasms (47 RCC, 8 PEComa, and 5 melanotic renal cancers). The ag… (full text at CIViC) PMID 26975036 · Argani et al., 2016 · Open in CIViC | civic |
| 〃 | Renal Cell Carcinoma with MiT Translocations | Diagnostic | B | Supports | ||||
| TFEB Fusion3 | ||||||||
| (diagnostic) | Renal Cell Carcinoma with MiT Translocations | Diagnostic | B | Supports Positive | 4 | accepted | EID11534Bakouny, et al. (2022) performed a comprehensive study of the molecular and clinical features of translocation renal cell carcinomas (tRCCs), defined as subtype of kidney cancer driven by MiT/TFE gene… (full text at CIViC) PMID 34986355 · Bakouny et al., 2022 · Open in CIViC | civic |
| 〃 | Renal Cell Carcinoma with MiT Translocations | Diagnostic | B | Supports Positive | 3 | accepted | EID11535Renal cell carcinomas (RCCs) with t(6;11)(p21;q12) are extremely rare and are characterized by a specific chromosome translocation involving the transcription factor EB (TFEB). Identification of eithe… (full text at CIViC) PMID 22895266 · Rao et al., 2012 · Open in CIViC | civic |
| 〃 | Renal Cell Carcinoma with MiT Translocations | Diagnostic | C | Supports | ||||
| TYK2 Fusion1 | ||||||||
| (diagnostic) | B Lymphoblastic Leukemia/Lymphoma, BCR-ABL1-Like | Diagnostic | C | Supports Positive | 4 | accepted | EID12803In this 2022 study, the authors investigate the oncogenic role of the MYB::TYK2 fusion gene in high-risk B-lymphoblastic leukemia (HR B-ALL). TYK2 rearrangements are identified as recurrent events in … (full text at CIViC) PMID 35022522 · Shirazi et al., 2022 · Open in CIViC | civic |
| WDR12 OVEREXPRESSION1 | ||||||||
| (prognostic) | GlioblastomaCURATED_BROADER | Prognostic | B | Supports Poor Outcome | 4 | submitted | EID8004Expression of WDR12 was found to be significantly higher in tumour than normal tissue from TCGA LGG and GBM datasets. Kaplan-Meier analysis showed high WDR12 expression to be significantly associated … (full text at CIViC) PMID 32180229 · Li et al., 2020 · Open in CIViC | civic |
| WEE1 Mutation1 | ||||||||
| (oncogenic) | Diffuse Large B-Cell LymphomaCURATED_BROADER | Oncogenic | E | Supports Oncogenicity | 3 | submitted | EID11995This gene was identified as recurrently mutated in an analysis of 574 DLBCL exomes. Incidence is less than 3% in most cohorts so its relevance remains unclear. PMID 29641966 · Schmitz et al., 2018 · Open in CIViC | civic |
| WEE1 Overexpression4 | ||||||||
| Adavosertib | Diffuse Midline Glioma, H3 K27-Altered | Predictive | D | Supports Sensitivity Response | 4 | submitted | EID7242Significant WEE1 protein overexpression was detected by IHC in VUMC-DIPG-1 tissue isolated from a patient's frontal lobe. Significant WEE1 protein levels were also found in E98-FM glioma cells. An i… (full text at CIViC) PMID 23270927 · Caretti et al., 2013 · Open in CIViC | civic |
| 〃 | Diffuse Midline Glioma, H3 K27-Altered | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID7243Two mouse xenograft models were used: one of tumor cells from a genetically engineered mouse with a BRAF V600E mutation, and the other using a patient's DIPG cells (SF8628). SF8628 was found to have … (full text at CIViC) PMID 24305702 · Mueller et al., 2014 · Open in CIViC | civic |
| 〃 | Esophageal Squamous Cell CarcinomaALIAS | Predictive | ||||||
| WEE1 RS39103841 | ||||||||
| Gemcitabine + Platinum CompoundCombination | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID814The presence of the WEE1 polymorphism rs3910384 correlated with OS and PFS of NSCLC patients treated with platinum-based chemotherapy. Especially the combination of two DNA-damaging agents was associa… (full text at CIViC) PMID 26057002 · Liu et al., 2015 · Open in CIViC | civic |
| WNK1 mutation1 | ||||||||
| (oncogenic) | Burkitt Lymphoma | Oncogenic | E | Supports Oncogenicity | 3 | submitted | EID11823Described in recent genome-wide study of BL and DLBCL PMID 36201743 · Thomas et al., 2023 · Open in CIViC | civic |
| WT1 Exon 7 Mutation2 | ||||||||
| (prognostic) | Acute Myeloid LeukemiaCURATED_BROADER | Prognostic | B | Does Not Support N/A | 4 | accepted | EID163Rates of complete remission and refractory disease are not different in patients with WT1 mutations (69% exon 7, 15% exon 9) than those without in young (16-60) patients with cytogenetically normal AM… (full text at CIViC) PMID 19221039 · Gaidzik et al., 2009 · Open in CIViC | civic |
| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Prognostic | B | Does Not Support N/A | 3 | accepted | EID162No differences in relapse-free or overall survival were identified between young (16-60) patients with or without WT1 mutations (69% exon 7, 15% exon 9) in cytogenetically normal AML. PMID 19221039 · Gaidzik et al., 2009 · Open in CIViC | civic |
Data updated 1 hour 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.
| A |
| Supports Sensitivity Response |
| 4 |
| accepted |
EID11233In an open-label, phase 1/2 trial on 87 patients with NSCLC including RET-fusion were given 400 mg once-daily oral pralsetinib, with the outcome measured as overall response rate. Overall responses we… (full text at CIViC) PMID 34118197 · Gainor et al., 2021 · Open in CIViC |
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| Selpercatinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 4 | submitted | EID11318In a follow up publication on the NCT03157128 clinical trial, results of 316 RET fusion positive NSCLC patients treated with the RET inhibitor selpercatinib were reported. Of note, this includes 144 … (full text at CIViC) PMID 36122315 · Drilon et al., 2023 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID7066In this phase 1 trial, 57 patients with RET fusion- or mutation positive cancers were treated in 7 dose levels. Among patients with RET-Fusion positive NSCLC, objective response rates were 65% (n = 17… (full text at CIViC) | civic |
| 〃 | Thyroid Gland Papillary CarcinomaALIAS | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID7069In this phase 1 trial, patients with RET-fusion or mutation positive cancers were treated with the selective RET-inhibitor selpercatinib (LOXO-292). Among the 6 patients with RET-fusion positive papil… (full text at CIViC) | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID8850Patients with RET-fusion positive non-small cell lung cancer were enrolled in this phase 1-2 trial of RET inhibitor selpercatinib. Among 105 consecutively enrolled patients who had previously received… (full text at CIViC) PMID 32846060 · Drilon et al., 2020 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | submitted | EID12135In this arm of the trial (NCT03157128), the intracranial objective response rate (iORR) was assessed in 80 patients with RET fusion-positive non-small cell lung cancer (NSCLC) treated with selpercatin… (full text at CIViC) PMID 34088726 · Subbiah et al., 2021 · Open in CIViC | civic |
| Vandetanib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID4848RET rearrangements involving RET are found in about 1% of NSCLC and define a unique molecular subset. This study was a multi-center, open-label, phase II clinical trial to examine the safety and effi… (full text at CIViC) PMID 27803005 · Lee et al., 2017 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID4849We aimed to assess the efficacy and safety of vandetanib in patients with advanced RET-rearranged NSCLC. In this open-label, multicentre, phase 2 trial (LURET), patients with advanced RET-rearranged N… (full text at CIViC) PMID 27825616 · Yoh et al., 2017 · Open in CIViC | civic |
| Predictive |
| A |
| Supports Sensitivity Response |
| 4 |
| accepted |
EID688An expansion cohort of a phase-1 Crizotinib study found a 72% objective response rate among 50 patients with ROS1 rearrangement. The study did not compare to patients without rearrangement that were t… (full text at CIViC) PMID 25264305 · Shaw et al., 2014 · Open in CIViC |
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| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 4 | accepted | EID7933A phase 2 clinical trial studied the efficacy of Crizotinib in East Asian NSCLC patients positive for ROS1 rearrangements (detected by RT-PCR AmoyDx assay) and negative for ALK1 rearrangements. Of the… (full text at CIViC) PMID 29596029 · Wu et al., 2018 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 3 | accepted | EID1030In a retrospective study, 30 patients were evaluated after crizotinib treatment for stage IV NSCLC confirmed for ROS1 rearrangement. On crizotinib, 24 of the patients achieved objective responses incl… (full text at CIViC) PMID 25667280 · Mazières et al., 2015 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 3 | submitted | EID8916The phase 2 EUCROSS trial (NCT02183870) examined the safety and efficacy of 250mg crizotinib twice daily in European ROS1-rearranged NSCLC patients. ROS1 status was assessed by break-apart FISH or bot… (full text at CIViC) PMID 30978502 · Michels et al., 2019 · Open in CIViC | civic |
| 〃 | Minimally Invasive Lung AdenocarcinomaALIAS | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID1443Study describes a 31-year old male, never-smoker patient with advanced NSCLC. Testing did not indicate tumor had EGFR mutation or ALK rearrangement. First line erlotininb did not yield a response. Aft… (full text at CIViC) PMID 22215748 · Bergethon et al., 2012 · Open in CIViC | civic |
| 〃 | Colorectal Adenocarcinoma | Predictive | E | Supports Sensitivity Response | 2 | accepted | EID1301A tissue microarray of 268 patients with histologically confirmed colorectal adenocarcinoma was performed to search for ROS1 gene fusion events to guide potential targeted therapy in future cases. Bre… (full text at CIViC) PMID 24296758 · Aisner et al., 2014 · Open in CIViC | civic |
| Entrectinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 5 | accepted | EID11123Describes 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 ROS-1 fusion-positive NSCLC (locally advanced or metastat… (full text at CIViC) PMID 31838015 · Drilon et al., 2020 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 3 | accepted | EID2951Two phase I studies included 119 patients with advanced or metastatic solid tumors, which included 28 patients with ROS1 rearrangements (n=28) where the overall safety and antitumor activity of entrec… (full text at CIViC) PMID 28183697 · Drilon et al., 2017 · Open in CIViC | civic |
| Lorlatinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | submitted | EID11335In this open-label, single-arm, phase 1-2 trial, 364 patients with histologically or cytologically confirmed advanced ROS1-positive NSCLC, with or without CNS metastases were assessed. Of them, 69 wit… (full text at CIViC) PMID 31669155 · Shaw et al., 2019 · Open in CIViC | civic |
| Repotrectinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 4 | submitted | EID12021In a phase 1-2 trial (NCT03093116), the ROS1/ALK/NTRK inhibitor repotrectinib demonstrated efficacy in NSCLC with ROS1 fusions. Among the 71 ROS1-inhibitor-naive patients, 56 (79%; 95% CI, 68 to 88) h… (full text at CIViC) PMID 38197815 · Drilon et al., 2024 · Open in CIViC | civic |
| Taletrectinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | submitted | EID12240The TRUST-I study (NCT04395677) was a phase II, multicenter, single-arm, open-label trial conducted in China to evaluate taletrectinib for ROS1 fusion-positive, locally advanced, or metastatic non-sma… (full text at CIViC) PMID 38822758 · Li et al., 2024 · Open in CIViC | civic |
| 4 |
| accepted |
EID11701Bakouny, 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 |
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| (prognostic) | Renal Cell Carcinoma with MiT Translocations | Prognostic | B | Supports Better Outcome | 2 | submitted | EID10164This study screened 983 Renal Cell Carcinoma (RCC) cases and identified 65 tumors with morphologic features suspicious of RCC with Xp11.2 translocation/TFE3 gene fusion (Xp11.2 RCC). TFE3 immunohistoc… (full text at CIViC) PMID 26169997 · He et al., 2015 · Open in CIViC | civic |
| 〃 | Renal Cell Carcinoma with MiT Translocations | Prognostic | C | Supports Poor Outcome | 4 | submitted | EID10149This study evaluates 200 nephrectomy cases. Within the 200 cases, there are four cases that are Xp11.2 translocation renal cell carcinomas (RCC). Previous studies identified two stages (pediatric and … (full text at CIViC) PMID 34917511 · Ge et al., 2021 · Open in CIViC | civic |
| (diagnostic) | Renal Cell Carcinoma with MiT Translocations | Diagnostic | C | Supports Positive | 2 | accepted | EID11683A study of 443 renal cell carcinoma identified 7 cases with an Xp11 translocation. The median age of the 7 patients was 41 years (range, 15 to 59 years). Of the 244 cases with a successful karyotype, … (full text at CIViC) PMID 19228722 · Komai et al., 2009 · Open in CIViC | civic |
| 2 |
| accepted |
EID11539A subset of renal neoplasms of children and young adults contains t(6;11)(p21;q12), fusion of the MALAT1 (Alpha) gene with the transcription factor gene TFEB. Argani, et al. (2005) included 7 renal ne… (full text at CIViC) PMID 15644781 · Argani et al., 2005 · Open in CIViC |
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| D |
| Supports Sensitivity Response |
| 3 |
| submitted |
EID9232Within a preclinical study the inhibitory effects of AZD1775 in esophageal squamous cell carcinoma (ESCC) was demonstrated in both in vitro and in-vivo samples that predominantly displayed high expres… (full text at CIViC) PMID 31427973 · Bi et al., 2019 · Open in CIViC |
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| 〃 | Acute Lymphoblastic Leukemia | Predictive | D | Does Not Support Sensitivity Response | 2 | submitted | EID9231Through a preclinical trial WEE1 expression evaluated in acute lymphoblastic leukemia cell lines (ALL) shows exceptionally high expression in samples (n=58, 44 diagnosis samples and 14 unpaired relaps… (full text at CIViC) PMID 30068368 · Ghelli Luserna Di Rorà et al., 2018 · Open in CIViC | civic |