t(5;12)(q13;p13) ?/ETV6
2013-12-01 Jean-Loup Huret Affiliation1.Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
Clinics and Pathology
Disease
Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), as well as acute lymphoblastic leukemia (ALL)
Phenotype stem cell origin
Five cases are available to date: 3 myeloid cases: an AML not otherwise specified, a M2-AML, and a RAEB transforming into M2-AML (Kobayashi et al., 1994; Yamamoto et al., 2000; Park et al., 2007); and 2 lymphoid cases: 2 ALLs (Heinonen et al., 1988; Sato et al., 1997). Is not taken into account in this review a case of translocation between 5q13, 12p13, 22q11, and 3q12 with no possible fusion transcript on any derivative chromosome, although ETV6 (12p13) and MN1 (22q12), with also sequences on 5q and on 3q are implicated in the rearrangements (Belloni et al., 2004). One case occurred after exposure to mutagenic agents: a patient experienced a renal carcinoma 3 years before onset of the secondary MDS (Yamamoto et al., 2000).
Epidemiology
The myeloid cases were a 58-year old female patient and two 65-year old male patients; the ALL cases were a 1-year old girl and a 12-year old girl.
Prognosis
Scarce data available: a M2-AML case was still alive but in relapse 9 months after diagnosis (Park et al., 2007), and the MDS case evolved towards a M2-AML and the patient died 4 months after diagnosis of the MDS (Yamamoto et al., 2000).
Genes Involved and Proteins
Note
The partner(s) of ETV6 in 5q13 remain(s) unknown. Both one myeloid and one lymphoid cases were tested, and it appears that the breakpoint in ETV6 is not identical: the breakpoint was located in intron 1, and exon 1 was deleted, in the treatment-related myeloid case (Yamamoto et al., 2000), whereas it was located 3 of the ETV6 coding sequence in an ALL case (Sato et al., 1997).
Gene name
ETV6 (ets variant 6)
Location
12p13.2
Protein description
452 amino acids. ETV6 is composed of a HLH domain responsible for hetero- and homodimerization in N-term, and an ETS domain responsible for sequence specific DNA-binding in C-term (binds to the DNA sequence 5-CCGGAAGT-3). Transcriptional regulator; tumor suppressor. Involved in bone marrow hematopoiesis.
Highly cited references
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 37686522 | 2023 | The Impact of ETV6-NTRK3 Oncogenic Gene Fusions on Molecular and Signaling Pathway Alterations. | 121 |
| 36766699 | 2023 | The Landscape of Secondary Genetic Rearrangements in Pediatric Patients with B-Cell Acute Lymphoblastic Leukemia with t(12;21). | 110 |
| 36350827 | 2023 | ETV6 Deficiency Unlocks ERG-Dependent Microsatellite Enhancers to Drive Aberrant Gene Activation in B-Lymphoblastic Leukemia. | 82 |
| 36658219 | 2023 | ETV6 dependency in Ewing sarcoma by antagonism of EWS-FLI1-mediated enhancer activation. | 75 |
| 36411286 | 2022 | Regulome analysis in B-acute lymphoblastic leukemia exposes Core Binding Factor addiction as a therapeutic vulnerability. | 71 |
| 28831010 | 2017 | Nasopharyngeal carcinoma super-enhancer-driven ETV6 correlates with prognosis. | 68 |
| 36543959 | 2023 | ETV3 and ETV6 enable monocyte differentiation into dendritic cells by repressing macrophage fate commitment. | 66 |
| 35198911 | 2022 | Identification of new ETV6 modulators through a high-throughput functional screening. | 66 |
| 34587239 | 2022 | t(4;12)(q12;p13) ETV6-rearranged AML without eosinophilia does not involve PDGFRA: relevance for imatinib insensitivity. | 66 |
| 37670323 | 2023 | RNA binding protein IGF2BP1 synergizes with ETV6-RUNX1 to drive oncogenic signaling in B-cell Acute Lymphoblastic Leukemia. | 65 |
| 35803545 | 2022 | Germline ETV6 mutation promotes inflammation and disrupts lymphoid development of early hematopoietic progenitors. | 63 |
| 34624096 | 2022 | ETV6-NCOA2 fusion induces T/myeloid mixed-phenotype leukemia through transformation of nonthymic hematopoietic progenitor cells. | 63 |
| 32326970 | 2020 | A novel ETV6-miR-429-CRKL regulatory circuitry contributes to aggressiveness of hepatocellular carcinoma. | 60 |
| 32841218 | 2020 | ETV6 germline mutations cause HDAC3/NCOR2 mislocalization and upregulation of interferon response genes. | 60 |
| 27229714 | 2016 | Characterization of leukemias with ETV6-ABL1 fusion. | 59 |
| 37469802 | 2023 | Optical Genome Mapping Identifies Novel Recurrent Structural Alterations in Childhood ETV6::RUNX1+ and High Hyperdiploid Acute Lymphoblastic Leukemia. | 59 |
| 28637624 | 2017 | ETV6 in hematopoiesis and leukemia predisposition. | 58 |
| 33450226 | 2021 | Biophysical characterization of the ETV6 PNT domain polymerization interfaces. | 58 |
| 26711002 | 2016 | Determination of ETV6-RUNX1 genomic breakpoint by next-generation sequencing. | 57 |
| 26102509 | 2015 | Germline ETV6 Mutations Confer Susceptibility to Acute Lymphoblastic Leukemia and Thrombocytopenia. | 55 |
| 39880832 | 2025 | Molecular and pharmacological heterogeneity of ETV6::RUNX1 acute lymphoblastic leukemia. | 55 |
| 30087163 | 2018 | Transcription factor Etv6 regulates functional differentiation of cross-presenting classical dendritic cells. | 55 |
| 36292767 | 2022 | Elevated ETV6 Expression in Glioma Promotes an Aggressive In Vitro Phenotype Associated with Shorter Patient Survival. | 52 |
| 31248877 | 2019 | ETV6-related thrombocytopenia and leukemia predisposition. | 51 |
| 32693409 | 2021 | Molecular basis of ETV6-mediated predisposition to childhood acute lymphoblastic leukemia. | 50 |
| 38356460 | 2024 | ETV6::ACSL6 translocation-driven super-enhancer activation leads to eosinophilia in acute lymphoblastic leukemia through IL-3 overexpression. | 50 |
| 25281506 | 2015 | ETV6 (TEL1) regulates embryonic hematopoiesis in zebrafish. | 50 |
| 37522715 | 2023 | ETV6 represses inflammatory response genes and regulates HSPC function during stress hematopoiesis in mice. | 48 |
| 31822803 | 2020 | Characterization of novel genetic alterations in salivary gland secretory carcinoma. | 48 |
| 28219927 | 2017 | Molecular role of the PAX5-ETV6 oncoprotein in promoting B-cell acute lymphoblastic leukemia. | 43 |
| 35685921 | 2022 | Low Prevalence of ETV6::RUNX1 Fusion Gene in a Hispanic Population. | 40 |
| 32957984 | 2020 | Clinicopathological findings of pediatric NTRK fusion mesenchymal tumors. | 38 |
| 9050885 | 1997 | Functional characterization of ETV6 and ETV6/CBFA2 in the regulation of the MCSFR proximal promoter. | 33 |
| 37895201 | 2023 | Complex Genomic Rearrangements Involving ETV6::ABL1 Gene Fusion in an Individual with Myeloid Neoplasm. | 33 |
| 29254279 | 2017 | Modeling the process of childhood ETV6-RUNX1 B-cell leukemias. | 31 |
| 30940639 | 2019 | Germline deletion of ETV6 in familial acute lymphoblastic leukemia. | 30 |
| 33677868 | 2021 | [Clinical features and prognosis of ETV6-RUNX1-positive childhood B-precursor acute lymphocyte leukemia]. | 29 |
| 23204479 | 2012 | Modeling ETV6-JAK2-induced leukemia: insights from the zebrafish. | 26 |
| 32406789 | 2021 | ETV6-related thrombocytopenia and platelet dysfunction. | 23 |
| 39101978 | 2024 | ETV6 Molecular Heterogeneity in Salivary Secretory Carcinoma: A Case Series Report and Literature Review. | 22 |
| 32723365 | 2020 | ETV6-ACSL6 fusion gene in myeloid neoplasms: clinical spectrum, current practice, and outcomes. | 22 |
| 38203288 | 2023 | ETV6::ABL1-Positive Myeloid Neoplasm: A Case of a Durable Response to Imatinib Mesylate without Additional or Previous Treatment. | 21 |
| 37503586 | 2023 | Myeloproliferative Neoplasm Driven by ETV6-ABL1 in an Adolescent with Recent History of Burkitt Leukemia. | 21 |
| 38952502 | 2024 | Mixed-phenotype (B-lymphocytic/myeloid) acute leukemia with ETV6-ABL1 expression. | 20 |
| 38806630 | 2024 | Backtracking NOM1::ETV6 fusion to neonatal pathogenesis of t(7;12) (q36;p13) infant AML. | 15 |
| 39066837 | 2024 | ETV6::ABL1 fusion: from overlooked minor clone in myeloproliferative neoplasm to major player in leukemic transformation. | 15 |
| 34535762 | 2022 | ETV6-RUNX1 and RUNX1 directly regulate RAG1 expression: one more step in the understanding of childhood B-cell acute lymphoblastic leukemia leukemogenesis. | 15 |
| 35586967 | 2022 | ETV6-related thrombocytopenia: dominant negative effect of mutations as common pathogenic mechanism. | 14 |
| 35537115 | 2022 | Clonal hematopoiesis in patients with ANKRD26 or ETV6 germline mutations. | 13 |
| 37381775 | 2023 | ETV6 fusions from insertions of exons 3-5 in pediatric hematologic malignancies. | 12 |
| 29471895 | 2018 | ETV6/FLT3 Fusion Is a Novel Client Protein of Hsp90. | 12 |
| 36538046 | 2023 | ETS Fight Club on Microsatellite Enhancers. | 10 |
| 37601849 | 2023 | Leukaemic cells expressing ETV6::FRK are sensitive to dasatinib in vivo. | 9 |
| 24335410 | 2014 | "There will be blood" from fibroblasts. | 8 |
| 26219557 | 2015 | ETV6 mutations define a new cancer predisposition syndrome. | 7 |
| 28299659 | 2017 | Mechanism of ETV6-RUNX1 Leukemia. | 0 |
| 33226740 | 1993 | ETV6 Thrombocytopenia and Predisposition to Leukemia. | 0 |
| 27450272 | 2017 | Transcription factor defects causing platelet disorders. | 0 |
| 28693791 | 2017 | ETV6 and ETV7: Siblings in hematopoiesis and its disruption in disease. | 0 |
| 38824653 | 2024 | ETV6::RUNX1-like Acute Lymphoblastic Leukemia. | 0 |
| 28555414 | 2017 | Germline ETV6 mutations and predisposition to hematological malignancies. | 0 |
| 29894279 | 2018 | Acute myeloid leukemia carrying ETV6 mutations: biologic and clinical features. | 0 |
| 37144345 | 2023 | The clinical and molecular spectrum of ETV6 mutated myeloid neoplasms. | 0 |
| 22578774 | 2012 | ETV6 fusion genes in hematological malignancies: a review. | 0 |
| 37085035 | 2023 | Single-cell analysis of megakaryopoiesis in peripheral CD34(+) cells: insights into ETV6-related thrombocytopenia. | 0 |
| 28299660 | 2017 | ETV6-RUNX1 (+) Acute Lymphoblastic Leukaemia in Identical Twins. | 0 |
| 15826831 | 2005 | ETV6: a versatile player in leukemogenesis. | 0 |
| 32836179 | 2020 | Siblings with ETV6/RUNX1-positive B-lymphoblastic leukemia: A single site experience and review of the literature. | 0 |
| 38629245 | 2024 | RAF1 gene fusions are recurrent driver events in infantile fibrosarcoma-like mesenchymal tumors. | 0 |
| 39017849 | 2024 | The Diverse Roles of ETV6 Alterations in B-Lymphoblastic Leukemia and Other Hematopoietic Cancers. | 0 |
| 32659251 | 2020 | ETV6 gene aberrations in non-haematological malignancies: A review highlighting ETV6 associated fusion genes in solid tumors. | 0 |
| 9031109 | 1996 | ETV6 gene rearrangements in hematopoietic malignant disorders. | 0 |
| 36069745 | 2022 | Myeloid neoplasm with ETV6::ACSl6 fusion: landscape of molecular and clinical features. | 0 |
| 33475741 | 2021 | Germline ETV6 variants: not ALL created equally. | 0 |
| 36274330 | 2022 | Myxoid spindle cell sarcoma with ETV6-NTRK3 fusion. | 0 |
| 37597896 | 2023 | Translate or differentiate? Molecular mechanisms of ETV6-related thrombocytopenia. | 0 |
| 35228392 | 2022 | ETV6 Regulates Hemin-Induced Erythroid Differentiation of K562 Cells through Mediating the Raf/MEK/ERK Pathway. | 0 |
| 29034503 | 2018 | Detection of a new heterozygous germline ETV6 mutation in a case with hyperdiploid acute lymphoblastic leukemia. | 0 |
| 9523202 | 1998 | The second ETV6 allele is not necessarily deleted in acute leukemias with a ETV6/ABL fusion. | 0 |
| 11173830 | 2000 | Fusion genes in leukemia: an emerging network. | 0 |
| 33396988 | 2021 | [ETV6-rearranged low-grade sinonasal non-intestinal-type adenocarcinoma: a clinicopathological analysis]. | 0 |
| 15826836 | 2005 | ETV6-NTRK3: a chimeric protein tyrosine kinase with transformation activity in multiple cell lineages. | 0 |
| 39138661 | 2025 | Correction to: ETV6::ABL1 fusion: from overlooked minor clone in myeloproliferative neoplasm to major player in leukemic transformation. | 0 |
| 38441775 | 2024 | Characteristics and literature review of ETV6::ABL1 fusion gene-positive acute myeloid leukemia. | 0 |
| 37157849 | 2023 | Cannibalism in an ETV6::RUNX1 paediatric B acute lymphoblastic leukaemia. | 0 |
| 39037342 | 2024 | Acute myeloid leukemia with ETV6::CHIC2 fusion gene: 'Pitfalls' in diagnosis. | 0 |
| 28063378 | 2017 | Overexpression of PTP4A3 in ETV6-RUNX1 acute lymphoblastic leukemia. | 0 |
| 25850516 | 2015 | Functional analysis of truncated forms of ETV6. | 0 |
| 11066076 | 2000 | t(7;12)(q36;p13), a new recurrent translocation involving ETV6 in infant leukemia. | 0 |
| 35787922 | 2022 | Therapeutic targeting of RBPJ, an upstream regulator of ETV6 gene, abrogates ETV6-NTRK3 fusion gene transformations in glioblastoma. | 0 |
| 33660258 | 2021 | Management of ETV6-ABL1-positive childhood acute lymphoblastic leukaemia: report of two cases, a literature review and a call for action. | 0 |
| 37985135 | 2024 | Platelet expression of the transcription factor ETV6 associates with ETV6-related thrombocytopenia and can be detected by immunofluorescence on the blood film. | 0 |
| 22373549 | 2012 | Detection of ETV6 gene rearrangements in adult acute lymphoblastic leukemia. | 0 |
| 21156245 | 2010 | B lymphoblastic leukemia with ETV6 amplification. | 0 |
| 38712034 | 2024 | Enigmatic missense mutations can cause disease via creation of de novo nuclear export signals. | 0 |
| 31482743 | 2020 | Myeloid neoplasm with eosinophilia and ETV6-JAK2 fusion. | 0 |
| 28395118 | 2017 | ETV6/RUNX1-like acute lymphoblastic leukemia: A novel B-cell precursor leukemia subtype associated with the CD27/CD44 immunophenotype. | 0 |
| 35506873 | 2022 | Apparent coexistence of ETV6::RUNX1 and KMT2A::MLLT3 fusions due to a nonproductive KMT2A rearrangement in B-ALL. | 0 |
| 33345679 | 2021 | A Multipronged Screening Approach Targeting Inhibition of ETV6 PNT Domain Polymerization. | 0 |
| 24740533 | 2014 | False positivity of ETV6/RUNX1 detected by FISH in healthy newborns and adults. | 0 |
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 15334551 | 2004 | A new complex rearrangement involving the ETV6, LOC115548, and MN1 genes in a case of acute myeloid leukemia. | Belloni E et al |
| 3181397 | 1988 | Cytogenetic study of 105 children with acute lymphoblastic leukemia. | Heinonen K et al |
| 7949101 | 1994 | Fluorescence in situ hybridization mapping of translocations and deletions involving the short arm of human chromosome 12 in malignant hematologic diseases. | Kobayashi H et al |
| 17854675 | 2007 | t(5;12)(q13;p13) in acute myeloid leukemia with preceding granulocytic sarcoma. | Park TS et al |
| 9389705 | 1997 | Heterogeneity in the breakpoints in balanced rearrangements involving band 12p13 in hematologic malignancies identified by fluorescence in situ hybridization: TEL (ETV6 ) is involved in only one half. | Sato Y et al |
| 10867145 | 2000 | Interstitial deletion of the short arm of chromosome 12 during clonal evolution in myelodysplastic syndrome with t(5;12)(q13;p13) involving the ETV6 gene. | Yamamoto K et al |
Citation
Jean-Loup Huret
t(5;12)(q13;p13) ?/ETV6
Atlas Genet Cytogenet Oncol Haematol. 2013-12-01
Online version: http://atlasgeneticsoncology.org/haematological/1662/gene-explorer/cancer-prone-explorer/meetings/helping-you
