t(16;21)(p11;q22) FUS/ERG

2005-01-01   Jean-Loup Huret 

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

Clinics and Pathology

Disease

de novo acute myeloid leukemia (AML); to be noted is one case of chronic myelogenous leukemia (CML) -blast crisis.

Phenotype stem cell origin

AML cases: mainly M1, M2, M4, M5a, M5b, or M7 AML; may be preceded by a myelodysplastic syndrome (MDS).

Epidemiology

about 40 reported cases, mainly found in young adults; children cases are described; median age is about 30 yrs; balanced sex ratio

Clinics

blood data: anemia, thrombocytopenia, mild hyperleucocytosis; with high monocytic cell count at times

Cytology

myelocytic and monocytoid features are often present; eosinophils in the bone marrow are sometimes abnormal and/or elevated; erythrophagocytosis may be found

Prognosis

seems poor: complete remission may not be achieved; there is high incidence of relapse within a year and a median of survival is about 22 months (cases herein reviewed)

Disease

Ewing tumours

Note

t(16;21)(p11;q22) has been found in rare cases of Ewing tumours, a paediatric neoplasm with small round-cells derived from neural crests cells usually associated with translocations involving EWSR1

Cytogenetics

Ewing tumours are usually associated with a t(11;22)(q24;q12) with 5 EWSR1 - 3 FLI1 involvement, less often associated with t(21;22)(q22;q12) with 5 EWSR1 - 3 ERG involvement, rarely associated with t(2;22)(q36; q12) (5 EWSR1 - 3 FEV) or with t(17;22)(q21;q12) (5 EWSR1-3 ETV4)

Prognosis

recent treatments have improved the prognosis of Ewings tumours. The prognosis is mainly determined by the presence of metastases at the time of diagnosis

Genes Involved and Proteins

Gene name
FUS (fusion involved in t (12;16) in malignant liposarcoma)
Location
16p11.2
Protein description
RNA binding protein; member of the TET family, like EWSR1
Gene name
ERG (v-ets erythroblastosis virus E26 oncogene like (avian))
Location
21q22.2
Protein description
ETS transcription factor

Result of the Chromosomal Anomaly

Description

5 FUS including exons 1 to 6, 7 or 8 - 3 ERG from exon 7, 8 or 9 to C-term.N-term FUS transactivation domain fused to the C-term DNA binding ETS domain of ERG

Oncogenesis

seems to act as a transcriptional activator

Highly cited references

Pubmed IDYearTitleCitations
106550652000Fus deficiency in mice results in defective B-lymphocyte development and activation, high levels of chromosomal instability and perinatal death.122
81870691994An RNA-binding protein gene, TLS/FUS, is fused to ERG in human myeloid leukemia with t(16;21) chromosomal translocation.59
129076332003FUS/ERG gene fusions in Ewing's tumors.57
79707321994TLS/FUS fusion domain of TLS/FUS-erg chimeric protein resulting from the t(16;21) chromosomal translocation in human myeloid leukemia functions as a transcriptional activation domain.52
186485442008IGF1 is a common target gene of Ewing's sarcoma fusion proteins in mesenchymal progenitor cells.50
272864592016Effective molecular targeting of CDK4/6 and IGF-1R in a rare FUS-ERG fusion CDKN2A-deletion doxorubicin-resistant Ewing's sarcoma patient-derived orthotopic xenograft (PDOX) nude-mouse model.47
176203872007Ewing sarcoma with novel translocation t(2;16) producing an in-frame fusion of FUS and FEV.38
92425521997Consistent detection of TLS/FUS-ERG chimeric transcripts in acute myeloid leukemia with t(16;21)(p11;q22) and identification of a novel transcript.31
91788861997Inhibition of apoptosis by normal and aberrant Fli-1 and erg proteins involved in human solid tumors and leukemias.30
75335291994Fusion of the FUS gene with ERG in acute myeloid leukemia with t(16;21)(p11;q22).26
266908692016Ewing sarcoma with ERG gene rearrangements: A molecular study focusing on the prevalence of FUS-ERG and common pitfalls in detecting EWSR1-ERG fusions by FISH.23
301502062018Prognostic impact of t(16;21)(p11;q22) and t(16;21)(q24;q22) in pediatric AML: a retrospective study by the I-BFM Study Group.16
292625512017The combination of temozolomide-irinotecan regresses a doxorubicin-resistant patient-derived orthotopic xenograft (PDOX) nude-mouse model of recurrent Ewing's sarcoma with a FUS-ERG fusion and CDKN2A deletion: Direction for third-line patient therapy.16
308953782019DNA methylation profiling distinguishes Ewing-like sarcoma with EWSR1-NFATc2 fusion from Ewing sarcoma.15
221405322011ERG deregulation induces PIM1 over-expression and aneuploidy in prostate epithelial cells.15
261482302016The oncofusion protein FUS-ERG targets key hematopoietic regulators and modulates the all-trans retinoic acid signaling pathway in t(16;21) acute myeloid leukemia.14
197376552009Ewing sarcoma-peripheral neuroectodermal tumor of the kidney with a FUS-ERG fusion transcript.14
93151041997Characteristic sequence motifs at the breakpoints of the hybrid genes FUS/CHOP, EWS/CHOP and FUS/ERG in myxoid liposarcoma and acute myeloid leukemia.13
232105732013Detection and clinical significance of gene rearrangements in Chinese patients with adult acute lymphoblastic leukemia.11
206948422010CD56 antigen expression and hemophagocytosis of leukemic cells in acute myeloid leukemia with t(16;21)(p11;q22).11
323620122020The clinical heterogeneity of round cell sarcomas with EWSR1/FUS gene fusions: Impact of gene fusion type on clinical features and outcome.10
324335082020Gain of chromosome 21 in hematological malignancies: lessons from studying leukemia in children with Down syndrome.10
318502342019Donor-Derived CD123-Targeted CAR T Cell Serves as a RIC Regimen for Haploidentical Transplantation in a Patient With FUS-ERG+ AML.10
302771152019Panoramic view of common fusion genes in a large cohort of Chinese de novo acute myeloid leukemia patients.9
240683732013Cryptic FUS-ERG fusion identified by RNA-sequencing in childhood acute myeloid leukemia.9
105236521999Dual transforming activities of the FUS (TLS)-ERG leukemia fusion protein conferred by two N-terminal domains of FUS (TLS).9
294271882018Molecular characteristic of acute leukemias with t(16;21)/FUS-ERG.8
290677512018Monitoring of fusion gene transcripts to predict relapse in pediatric acute myeloid leukemia.6
292258302017Acute basophilic leukemia associated with the t(16;21)(p11;q22)/FUS-ERG fusion gene.6
90967021997Establishment of a novel human acute myeloblastic leukemia cell line (YNH-1) with t(16;21), t(1;16) and 12q13 translocations.6
243747192014RUNX1 mutation associated with clonal evolution in relapsed pediatric acute myeloid leukemia with t(16;21)(p11;q22).5
197814432009Detection of FUS-ERG chimeric transcript in two cases of acute myeloid leukemia with t(16;21)(p11.2;q22) with unusual characteristics.5
162635892005TLS/FUS-ERG fusion gene in acute lymphoblastic leukemia with t(16;21)(p11;q22) and monitoring of minimal residual disease.5
299594362019Allogeneic hematopoietic stem cell transplantation for children and adolescents with high-risk cytogenetic AML: distinctly poor outcomes of FUS-ERG-positive cases.4
271831482016A t(16;21)(p11;q22) in Acute Myeloid Leukemia (AML) Resulting in Fusion of the FUS/TLS and ERG Genes: A Review of the Literature.4
103541361999Myeloid differentiation antigen and cytokine receptor expression on acute myelocytic leukaemia cells with t(16;21)(p11;q22): frequent expression of CD56 and interleukin-2 receptor alpha chain.4
286819982018Eribulin regresses a doxorubicin-resistant Ewing's sarcoma with a FUS-ERG fusion and CDKN2A-deletion in a patient-derived orthotopic xenograft (PDOX) nude mouse model.3
206206042010Two childhood cases of acute leukemia with t(16;21)(p11.2;q22): second case report of infantile acute lymphoblastic leukemia with unusual type of FUS-ERG chimeric transcript.3
113402532001Detection of minimal residual disease in a patient having acute myelogenous leukemia with t(16;21)(p11;q22) treated by allogeneic bone marrow transplantation.3
258301332015A case of pediatric ALL with t(16;21)(p11.2;q22) and FUS-ERG rearrangement.2
198933462009[Two cases of acute myeloid leukemia with t(16;21)(p11;q22) and TLS/FUS-ERG fusion transcripts].2
115055302001[AML(M7) associated with t(16;21)(p11;q22) showing relapse after unrelated bone marrow transplantation and disappearance of TLS/FUS-ERG mRNA].2
337080412021Distribution of fusion transcripts and its clinical impact in patients with acute myeloid leukemia in Sudan.1
317882682019Salvage therapy with azacitidine for pediatric acute myeloid leukemia with t(16;21)(p11;q22)/FUS-ERG and early relapse after allogeneic blood stem cell transplantation: A case report.1
167379202006Unusual type of TLS/FUS-ERG chimeric transcript in a pediatric acute myelocytic leukemia with 47,XX,+10,t(16;21)(p11;q22).1
357388862022Gene of the month: ERG.0
355032612022A novel HNRNPH1::ERG rearrangement in aggressive acute myeloid leukemia.0
347475542022Endobronchial ultrasound-guided fine needle aspiration diagnosis of metastatic FUS-ERG-rearranged extraskeletal Ewing sarcoma following 15 years of untreated metastatic recurrence.0
338946452021Rare and favorable prognosis of pediatric acute lymphoblastic leukemia with TLS-ERG fusion gene: Case report with long-term follow-up and review of literature.0
338685292021Radiological and pathological diagnosis of an incidental Askin tumor.0
334423612020Sinonasal FUS-ERG-Rearranged Ewing's Sarcoma Mimicking Glomangiopericytoma.0
331863482020Acute myeloid leukemia associated with t(16:21)(p11;q22) in a pediatric patient.0
287669062017CD66c (KOR-SA3544) antigen expression of leukemic blasts in pediatric acute myeloid leukemia with TLS/FUS-ERG fusion transcript.0
270337582016[Clinical characteristics of acute myeloid leukemia with t (16;21) (p11;q22):nine cases report and literature review].0
267708122016FUS-ERG gene fusion in isolated myeloid sarcoma showing uncommon clinical features.0
215362422011Establishment and characterization of a novel acute myeloid leukemia cell line, JIH-4, carrying a t(16;21)(p11.2;q22) and expressing the FUS-ERG fusion.0

Bibliography

Pubmed IDLast YearTitleAuthors
23576841990Acute nonlymphocytic leukemia with t(16;21)Berkowicz M et al
120913562002Cytogenetic profile of childhood and adult megakaryoblastic leukemia (M7): a study of the Groupe Français de Cytogénétique Hématologique (GFCH).Dastugue N et al
16065691992t(16;21) in a Ph positive CML.Ferro MR et al
95498301997Detection of minimal residual disease in cerebro-spinal fluid of a patient with acute myelogenous leukemia with t(16;21)(p11;q22) translocation by reverse transcriptase-polymerase chain reaction.Harigae H et al
146549492004Breakpoint differentiation in chromosomal aberrations of hematological malignancies: Identification of 33 previously unrecorded breakpoints.Heller A et al
87198981995Acute non-lymphoblastic leukaemia with t(16;21): case report with a review of the literature.Hiyoshi M et al
77947651995Establishment and characterization of IRTA17 and IRTA21, two novel acute non-lymphocytic leukaemia cell lines with t(16;21) translocation.Hiyoshi M et al
104464931999Hemophagocytosis by leukemic blasts in a case of acute megakaryoblastic leukemia with t(16;21)(p11;q22).Imashuku S et al
92425521997Consistent detection of TLS/FUS-ERG chimeric transcripts in acute myeloid leukemia with t(16;21)(p11;q22) and identification of a novel transcript.Kong XT et al
20653161991Translocation (16;21)(p11;q22) in acute monoblastic leukemia with erythrophagocytosis.Marosi C et al
84531031993The 8;21 chromosome translocation in acute myeloid leukemia is always detectable by molecular analysis using AML1.Maseki N et al
38602821985Acute nonlymphoblastic leukemia with bone marrow eosinophilia and structural anomaly of chromosome 16.Mecucci C et al
31642431988Translocation (8;21) and its variants in acute nonlymphocytic leukemia. The relative importance of chromosomes 8 and 21 to the genesis of the disease.Minamihisamatsu M et al
20366421991t(16;21)(p11.2;q22): a recurrent primary rearrangement in ANLL.Morgan R et al
82425971993Acute non-lymphocytic leukemia with t(16;21).Nobbs MC et al
80391661994Translocation (16;21)(p11;q22) in acute nonlymphocytic leukemia.Okada K et al
106346492000Acute myeloid leukemia possessing jumping translocation is related to highly elevated levels of EAT/mcl-1, a Bcl-2 related gene with anti-apoptotic functions.Okita H et al
75335291994Fusion of the FUS gene with ERG in acute myeloid leukemia with t(16;21)(p11;q22).Panagopoulos I et al
105720831999Chromosomal abnormalities in 478 children with acute myeloid leukemia: clinical characteristics and treatment outcome in a cooperative pediatric oncology group study-POG 8821.Raimondi SC et al
2125791199016;21 translocation in acute nonlymphocytic leukemia with abnormal eosinophils: a unique subtype.Sadamori N et al
81391141994[Acute monoblastic leukemia (M5a) with dysmegakaryocytopoiesis associated with t(16;21) (p11;q22)].Satoh K et al
75172111994HLA-DR-, CD33+, CD56+, CD16- myeloid/natural killer cell acute leukemia: a previously unrecognized form of acute leukemia potentially misdiagnosed as French-American-British acute myeloid leukemia-M3.Scott AA et al
103541361999Myeloid differentiation antigen and cytokine receptor expression on acute myelocytic leukaemia cells with t(16;21)(p11;q22): frequent expression of CD56 and interleukin-2 receptor alpha chain.Shikami M et al
129076332003FUS/ERG gene fusions in Ewing's tumors.Shing DC et al
95921831998Cytogenetic analysis of de novo acute myeloid leukemia with trilineage myelodysplasia in comparison with myelodysplastic syndrome evolving to acute myeloid leukemia.Tamura S et al

Summary

Fusion gene

FUS/ERG FUS (16p11.2) ERG (21q22.2) M t(16;21)(p11;q22) t(16;21;22)(p11;q22;p11)|FUS/ERG FUS (16p11.2) ERG (21q22.2) TIC
Atlas Image
t(16;21)(p11;q22) G- banding - Courtesy Melanie Zenger and Claudia Haferlach.

Citation

Jean-Loup Huret

t(16;21)(p11;q22) FUS/ERG

Atlas Genet Cytogenet Oncol Haematol. 2005-01-01

Online version: http://atlasgeneticsoncology.org/haematological/1037/t(16;21)(p11;q22)

Historical Card

1998-02-01 t(16;21)(p11;q22) FUS/ERG by  Christine Pérot 

External Links