Download Gene Section FGA7 (Fused Gene 7 to AML1) in Oncology and Haematology

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FGA7 (Fused Gene 7 to AML1)
Fady M Mikhail, Giuseppina Nucifora
23 Francis Street, Apt 18, Boulkely, Alexandria, Egypt (FMM, GN)
Published in Atlas Database: June 2004
Online updated version: http://AtlasGeneticsOncology.org/Genes/FGA7ID525.html
DOI: 10.4267/2042/38101
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.
© 2004 Atlas of Genetics and Cytogenetics in Oncology and Haematology
FGA7 sequence is contained within three human
genomic BAC clones: RP11-104M2, RP11-153C5, and
RP11-595L6.
t(4;21)(q28;q22) generates two fusion transcripts due to
alternative splicing of AML1. Transcript I contains
AML1 exon 5 fused to FGA7, whereas transcript II
contains AML1 exon 6 fused to FGA7.
Identity
Location: 4q28
Protein
Description
AML1-FGA7 fusion encodes two variant chimeric
proteins, both of which consist of the N-terminus of
AML1 including the RUNT domain, but differ in the
inclusion of AML1 exon 6. Both predicted proteins
contain an identical C-terminus derived from FGA7
that adds 27 amino acids after the AML1 breakpoint.
Metaphase FISH analysis using the BAC probe RP11-104M2
labeled with FITC (green) hybridized to a normal metaphase
cell confirms the chromosomal localization of the probe (gene)
to 4q28.
Expression
DNA/RNA
FGA7 is not expressed in normal hematopoietic tissue.
It is expressed in skeletal muscle and ovarian tissues
with a transcript size of about 11kb.
Description
The gene has not been fully cloned at the present time.
A 476-base novel sequence fused to AML1 has been
identified and sequenced as a result of the molecular
cloning of the t(4;21)(q28;q22). The novel sequence
maps to chromosome band 4q28. Sequence analysis did
not show any significant homology with any of the
known genes in the human GenBank DNA database.
However the first 118-bases are identical to a part of
human ovarian EST-11116119. Also, the first 196bases of the sequence show 87% homology with a
mouse sequence, whereas the first 237-bases show 85%
homology with a rat sequence. Based on the high
degree of identity among the three species, it is very
likely that the novel sequence represents a part of a
novel gene, which was named FGA7.
Atlas Genet Cytogenet Oncol Haematol. 2004; 8(3)
Homology
FGA7 shows high homology to mouse and rat
sequences.
Implicated in
t(4;21)(q28;q22) leading to AML1-FGA7
gene fusion
Disease
Pediatric T-cell ALL.
Prognosis
Poor.
Cytogenetics
Associated with del(7)(q22).
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FGA7 (Fused Gene 7 to AML1)
Mikhail FM, Nucifora G
Oncogenesis
The predicted AML1-FGA7 chimeric proteins contain
a limited number of amino acid residues fused to
AML1 in a situation similar to that reported for AML1EAP fusion that is a product of t(3;21). It is possible
that the expression of a constitutively shortened AML1
could compete with full-length AML1 and act as a
dominant negative inhibitor of the promoters that the
core binding factor (CBF) activates.
Schematic representation of AML1 and AML1-FGA7 fusion
transcripts. Top, diagram of AML1 shows the RUNT domain
(RD) and the transactivation domain (TA) separated by exon 6.
Center, the fusion of AML1 exon 6 to FGA7 results in the
addition of 27 codons. The asterisks indicate the stop codon.
Bottom, the alternative splice form that does not include exon 6
is shown.
References
Mikhail FM, Serry KA, Hatem N, Mourad ZI, Farawela HM, El
Kaffash DM, Coignet L, Nucifora G. A new translocation that
rearranges the AML1 gene in a patient with T-cell acute
lymphoblastic leukemia. Cancer Genet Cytogenet. 2002
May;135(1):96-100
Mikhail FM, Coignet L, Hatem N, Mourad ZI, Farawela HM, El
Kaffash DM, Farahat N, Nucifora G. A novel gene, FGA7, is
fused to RUNX1/AML1 in a t(4;21)(q28;q22) in a patient with Tcell acute lymphoblastic leukemia. Genes Chromosomes
Cancer. 2004 Feb;39(2):110-8
Metaphase FISH analysis using the BAC probe RP11-104M2
hybridized to the patient's metaphase shows one normal green
signal on the intact chromosome 4 (dashed arrow) and two
smaller green signals on der(21) (arrowhead) and on der(4)
(arrow) as a result of the t(4;21)(q28;q22).
Atlas Genet Cytogenet Oncol Haematol. 2004; 8(3)
This article should be referenced as such:
Mikhail FM, Nucifora G. FGA7 (Fused Gene 7 to AML1). Atlas
Genet Cytogenet Oncol Haematol. 2004; 8(3):223-224.
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