t(5;12)(q13;p13) ?/ETV6

2013-12-01   Jean-Loup Huret 

1.Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

Clinics and Pathology


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).


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.


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

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)
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 IDYearTitleCitations
356722772022Identification of a novel PHIP::BRAF gene fusion in infantile fibrosarcoma.0
352588552022JACLS ALL-02 SR protocol reduced-intensity chemotherapy produces excellent outcomes in patients with low-risk childhood acute lymphoblastic leukemia.0
351563432022Cytological and molecular characterization of secretory breast carcinoma.0
346554082022Secretory Carcinoma of the Thyroid in a 49-Year-Old Man Treated with Larotrectinib: Protracted Clinical Course of Disease Despite the High-Grade Histologic Features.0
328355762022The Giant Infantile Fibrosarcoma of Fetal Oropharynx and Anterior Neck.0
357371552022Prediction of EVT6-NTRK3-Dependent Papillary Thyroid Cancer Using Minor Expression Profile.0
356708542022Low-grade tracheal adenocarcinoma with ETV6::NTRK3 fusion: unique morphology akin to subsets of sinonasal low-grade non-intestinal-type adenocarcinoma.0
352499922022Clear Cell Neoplasms of Salivary Glands: A Diagnostic Challenge.0
342552772022An Underappreciated Cytomorphological Feature of Secretory Carcinoma of Salivary Gland on Fine Needle Aspiration Biopsy: Case Report with Literature Review.0
357204852022A unique case of inflammatory myofibroblastic tumor of the liver manifesting with biloma: A case report.0
356859212022Low Prevalence of ETV6::RUNX1 Fusion Gene in a Hispanic Population.0
356460482022Whole-Genome/Exome Sequencing Uncovers Mutations and Copy Number Variations in Primary Diffuse Large B-Cell Lymphoma of the Central Nervous System.0
356441952022[Clinical features and prognosis of childhood B-lineage acute lymphoblastic leukemia expressing the PRAME gene].0
356122712022Clinical implications and genetic features of clonal cytopenia of undetermined significance compared to lower-risk myelodysplastic syndrome.0
356106282022Mutational landscape of chronic myelomonocytic leukemia in Chinese patients.0
355869672022ETV6-related thrombocytopenia: dominant negative effect of mutations as common pathogenic mechanism.0
355371152022Clonal hematopoiesis in patients with ANKRD26 or ETV6 germline mutations.0
355367332022Larotrectinib Treatment for Patients With TRK Fusion-Positive Salivary Gland Cancers.0
351068562022Fusion-associated carcinomas of the breast: Diagnostic, prognostic, and therapeutic significance.0
344865432022Secretory Carcinoma of the Salivary Gland: A Rarity in Children.0
357354232022TRK Inhibition with Entrectinib in Metastatic Salivary Secretory Carcinoma (SC): A Case Report.0
357126322022Immunoglobulin Heavy Chain High-Throughput Sequencing in Pediatric B-Precursor Acute Lymphoblastic Leukemia: Is the Clonality of the Disease at Diagnosis Related to Its Prognosis?0
355430762022Histologic characterization of paediatric mesenchymal neoplasms treated with kinase-targeted therapy.0
355116472022[Low-grade non-intestinal adenocarcinoma of the nasal cavity and paranasal sinuses with ETV6 gene rearrangement:report of a case].0
355068732022Apparent coexistence of ETV6::RUNX1 and KMT2A::MLLT3 fusions due to a nonproductive KMT2A rearrangement in B-ALL.0
347873762022Philadelphia-like acute lymphoblastic leukemia: Characterization in a pediatric cohort in a referral center in Colombia.0
355740462022Fibrous hamartoma of infancy with sarcomatous transformation: an unusual morphology.0
353935132022mRNA-miRNA bipartite networks reconstruction in different tissues of bladder cancer based on gene co-expression network analysis.0
352947222022In Utero Development and Immunosurveillance of B Cell Acute Lymphoblastic Leukemia.0
349534442022Mammary analogue secretory carcinoma: A challenging case arising in a young man with radiation exposure.0
348713732022Impact of high-risk cytogenetics on outcomes for children and young adults receiving CD19-directed CAR T-cell therapy.0
335263732022Precursor B-lineage acute lymphoblastic leukemia patients with aberrant natural killer cell and T cell - lineage antigen expression: experience from a tertiary cancer care center.0
355664072022Machine Learning Based Analysis of Relations between Antigen Expression and Genetic Aberrations in Childhood B-Cell Precursor Acute Lymphoblastic Leukaemia.0
355629652022Multi-Cohort Transcriptomic Subtyping of B-Cell Acute Lymphoblastic Leukemia.0
354838762022Acute myeloid leukemia with an MN1-ETV6 fusion in a young child with Down syndrome.0
354266802022Discovery of the First Highly Selective and Broadly Effective Macrocycle-Based Type II TRK Inhibitors that Overcome Clinically Acquired Resistance.0
353856042022Secretory carcinoma of the salivary gland, a rare entity: An international multi-institutional study.0
353848762022Using pan-TRK and RET Immunohistochemistry for the Detection of Fusion Types of Salivary Gland Secretory Carcinoma.0
351927452022Genetic analysis and clinical significance of a rare t(1;12)(q21;p13) in a patient with high-risk myelodysplastic syndrome.1
350328962022Infantile fibrosarcoma with an EGFR kinase domain duplication: Underlining a close relationship with congenital mesoblastic nephroma and highlighting a similar morphological spectrum.0
349828292022A somatic UBA2 variant preceded ETV6-RUNX1 in the concordant BCP-ALL of monozygotic twins.0
349793552022t(5;12)(q31;p13)/ETV6::ACSL6 and t(6;9)(p23;q34)/DEK::NUP214 concurrence in acute myeloid leukemia: an unusual association of two rare abnormalities.0
348733002022Focal disruption of DNA methylation dynamics at enhancers in IDH-mutant AML cells.2
353266132022Towards a Molecular Classification of Sinonasal Carcinomas: Clinical Implications and Opportunities.1
353002162022The Mutation of BTG2 Gene Predicts a Poor Outcome in Primary Testicular Diffuse Large B-Cell Lymphoma.0
351069362022SGK1 mutation status can further stratify patients with germinal center B-cell-like diffuse large B-cell lymphoma into different prognostic subgroups.1
351026302022NTRK gene fusions are detected in both secretory and non-secretory breast cancers.0
349991802022Identification of diagnosis and prognosis gene markers in B-ALL with ETV6-RUNX1 fusion by integrated bioinformatics analysis.0
349157532022Unique Molecular Signatures Are Associated with Aggressive Histology in Pediatric Differentiated Thyroid Cancer.0
342313372022Diagnostic challenges and successful organ-preserving therapy in a case of secretory carcinoma of minor salivary glands.2
354257002022A Nomogram for Predicting Event-Free Survival in Childhood Acute Lymphoblastic Leukemia: A Multicenter Retrospective Study.0
353221952022Low-grade non-intestinal-type sinonasal adenocarcinoma: a histologically distinctive but molecularly heterogeneous entity.0
352670842022The evolving role of molecular pathology in the diagnosis of salivary gland tumours with potential pitfalls.0
351581212022Genomic landscape of secretory carcinoma of the breast with axillary lymph node metastasis.0
350844342022Association of Genetic Ancestry With the Molecular Subtypes and Prognosis of Childhood Acute Lymphoblastic Leukemia.3
346571282022Prognostic impact of chromosomal abnormalities and copy number alterations in adult B-cell precursor acute lymphoblastic leukaemia: a UKALL14 study.0
346063892022Secretory Carcinoma in Children and Young Adults: A Case Series.0
344488232022The molecular hallmarks of primary and secondary vitreoretinal lymphoma.1
352956132022NTRK Fusions Detection in Paediatric Sarcomas to Expand the Morphological Spectrum and Clinical Relevance of Selected Entities.0
351989112022Identification of new ETV6 modulators through a high-throughput functional screening.0
349333432022Whole-transcriptome analysis in acute lymphoblastic leukemia: a report from the DFCI ALL Consortium Protocol 16-001.1
349814322022Newly diagnosed ETV6-RUNX1-positive B-acute lymphoblastic leukemia localized to the left pelvic bone marrow.0
346174332022Characterization of Immunophenotypic Aberrancies with Respect to Common Fusion Transcripts in B-Cell Precursor Acute Lymphoblastic Leukemia: A Report of 986 Indian Patients0
345357622022ETV6-RUNX1 and RUNX1 directly regulate RAG1 expression: one more step in the understanding of childhood B-cell acute lymphoblastic leukemia leukemogenesis.0
352052402022Investigation of the Genetic Architecture of Pigs Subjected to Breeding Intensification.0
349919232022Primitive myxoid mesenchymal tumor of infancy: Case report and review of the literature.0
349585032022Mesenchymal neoplasms with NTRK and other kinase gene alterations.0
347940692022NTRK-Rearranged soft tissue neoplasms: A review of evolving diagnostic entities and algorithmic detection methods.0
347810942022Utilizing next-generation sequencing to characterize a case of acute myeloid leukemia with t(4;12)(q12;p13) in the absence of ETV6/CHIC2 and ETV6/PDGFRA gene fusions.0
347271702022Decreased IL-10 accelerates B-cell leukemia/lymphoma in a mouse model of pediatric lymphoid leukemia.0
346240962022ETV6-NCOA2 fusion induces T/myeloid mixed-phenotype leukemia through transformation of nonthymic hematopoietic progenitor cells.1
353069212022ETS variant transcription factor 6 enhances oxidized low-density lipoprotein-induced inflammatory response in atherosclerotic macrophages via activating NF-κB signaling.0
352426632022Cellular congenital mesoblastic nephroma detected by prenatal MRI: a case report and literature review.0
352283922022ETV6 Regulates Hemin-Induced Erythroid Differentiation of K562 Cells through Mediating the Raf/MEK/ERK Pathway.0
351587432022Recent Advances on Immunohistochemistry and Molecular Biology for the Diagnosis of Adnexal Sweat Gland Tumors.0
350749942022Erythrophagocytosis in a patient with B-cell acute lymphoblastic leukemia with t(12;21) (p13.2; q22.1); ETV6-RUNX1: Case report and review of the literature.0
350535002022High ETV6 Levels Support Aggressive B Lymphoma Cell Survival and Predict Poor Outcome in Diffuse Large B-Cell Lymphoma Patients.0
350442922022Infantile Fibrosarcoma and Other Spindle Cell Neoplasms of Infancy. A Review of Morphologically Overlapping yet Molecularly Distinctive Entities.0
349915632022Clinicopathological investigation of secretory carcinoma cases including a successful treatment outcome using entrectinib for high-grade transformation: a case report.0
348193032022Hi-C detects genomic structural variants in peripheral blood of pediatric leukemia patients.0
345974662022Clonal dynamics in pediatric B-cell precursor acute lymphoblastic leukemia with very early relapse.3
345912922022Successful treatment of hepatosplenic T-cell lymphoma with fludarabine, high-dose cytarabine and subsequent unrelated umbilical cord blood transplantation.0
345872392022t(4;12)(q12;p13) ETV6-rearranged AML without eosinophilia does not involve PDGFRA: relevance for imatinib insensitivity.0
350046012021Risk Factors for Childhood Leukemia: Radiation and Beyond.2
349880262021Prognostic Value and Outcome for ETV6/RUNX1-Positive Pediatric Acute Lymphoblastic Leukemia: A Report From the South China Children's Leukemia Group.1
345519052021Comprehensive Molecular Analysis of Inflammatory Myofibroblastic Tumors Reveals Diverse Genomic Landscape and Potential Predictive Markers for Response to Crizotinib.0
345477662021Distinct clinical characteristics of DUX4- and PAX5-altered childhood B-lymphoblastic leukemia.0
344599812021RAF1-rearranged spindle cell tumour: report of two additional cases with identification of a novel FMR1-RAF1 fusion.0
344025292021NTRK oncogenic fusions are exclusively associated with the serrated neoplasia pathway in the colorectum and begin to occur in sessile serrated lesions.2
343782832021An unusual fusion gene EML4-ALK in a patient with congenital mesoblastic nephroma.0
343714362021Proposal and clinical application of molecular genetic risk scoring system, "MRplus", for BCR-ABL1 negative pediatric B-cell acute lymphoblastic leukemia- report from a single centre.1
333943792021A Poorly Differentiated Non-keratinizing Sinonasal Squamous Cell Carcinoma with a Novel ETV6-TNFRSF8 Fusion Gene.1
349435212021Cytopathological Findings of Secretory Carcinoma of the Salivary Gland and the Diagnostic Utility of Giemsa Staining.0
348284362021Genomewide Association Analyses of Lactation Persistency and Milk Production Traits in Holstein Cattle Based on Imputed Whole-Genome Sequence Data.0
347905772021Anti-Tumor Activity of AZD4547 Against NTRK1 Fusion Positive Cancer Cells Through Inhibition of NTRKs.0
347539262021Cancer drivers and clonal dynamics in acute lymphoblastic leukaemia subtypes.1
345701792021Mutational patterns and their correlation to CHIP-related mutations and age in hematological malignancies.2
349401232021Molecular Genetics of Pre-B Acute Lymphoblastic Leukemia Sister Cell Lines during Disease Progression.0
348849972021Integrated Clinical Genotype-Phenotype Characteristics of Blastic Plasmacytoid Dendritic Cell Neoplasm.0
348308092021Transcriptional and Mutational Profiling of B-Other Acute Lymphoblastic Leukemia for Improved Diagnostics.1


Pubmed IDLast YearTitleAuthors
153345512004A new complex rearrangement involving the ETV6, LOC115548, and MN1 genes in a case of acute myeloid leukemia.Belloni E et al
31813971988Cytogenetic study of 105 children with acute lymphoblastic leukemia.Heinonen K et al
79491011994Fluorescence in situ hybridization mapping of translocations and deletions involving the short arm of human chromosome 12 in malignant hematologic diseases.Kobayashi H et al
178546752007t(5;12)(q13;p13) in acute myeloid leukemia with preceding granulocytic sarcoma.Park TS et al
93897051997Heterogeneity 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
108671452000Interstitial 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


Jean-Loup Huret

t(5;12)(q13;p13) ?/ETV6

Atlas Genet Cytogenet Oncol Haematol. 2013-12-01

Online version: http://atlasgeneticsoncology.org/haematological/1662/t(5;12)(q13;p13)-etv6

External Links