FGA7 (Fused Gene 7 to AML1)

Identity

HGNC
Location	4q28
	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.

DNA/RNA

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 196-bases 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. 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.

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.
Expression	FGA7 is not expressed in normal hematopoietic tissue. It is expressed in skeletal muscle and ovarian tissues with a transcript size of about 11kb.
Homology	FGA7 shows high homology to mouse and rat sequences.

Implicated in

Entity	t(4;21)(q28;q22) leading to AML1-FGA7 gene fusion
Disease	Pediatric T-cell ALL.
Prognosis	Poor.
Cytogenetics	Associated with del(7)(q22).
	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.
	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).
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 AML1-EAP 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.

External links

	Nomenclature
HGNC	-   -
Entrez_Gene	FGA7  -  -
	Cards
Atlas	FGA7ID525
GeneCards	FGA7
Ensembl	FGA7 [Search_View]    [Gene_View]
Genatlas	FGA7
GeneLynx	FGA7
eGenome	FGA7
euGene	-
	Genomic and cartography
GoldenPath	FGA7  -  4q28   chr4:138753188-138753105 -  4q28   [Description]    (hg18-Mar_2006)
Ensembl	FGA7 - 4q28 [CytoView]
NCBI	Mapview
HomoloGene	FGA7
	Gene and transcription
Genbank	- [ ENTREZ ]
AceView	FGA7 AceView - NCBI
	Protein : pattern, domain, 3D structure
	Protein Interaction databases
	Polymorphism : SNP, mutations, diseases
SNP	FGA7 [dbSNP-NCBI]
SNP	FGA7 [GeneSNPs - Utah]  FGA7] [HGBASE - SRS]
HAPMAP	FGA7 [HAPMAP]
HGMD	-
	General knowledge
Family Browser	FGA7 [UCSC Family Browser]
PubGene	FGA7
TreeFam	-
CTD	- [Comparative ToxicoGenomics Database]
	Other databases
	Probes
	PubMed

Bibliography

A new translocation that rearranges the AML1 gene in a patient with T-cell acute lymphoblastic leukemia.

Mikhail FM, Serry KA, Hatem N, Mourad ZI, Farawela HM, El Kaffash DM, Coignet L, Nucifora G

Cancer genetics and cytogenetics. 2002 ; 135 (1) : 96-100.

PMID 12072207

A novel gene, FGA7, is fused to RUNX1/AML1 in a t(4;21)(q28;q22) in a patient with T-cell acute lymphoblastic leukemia.

Mikhail FM, Coignet L, Hatem N, Mourad ZI, Farawela HM, El Kaffash DM, Farahat N, Nucifora G

Genes, chromosomes & cancer. 2004 ; 39 (2) : 110-118.

PMID 14695990

REVIEW articles	automatic search in PubMed
Last year publications	automatic search in PubMed

Search in all EBI   NCBI

Contributor(s)

Written	06-2004	Fady M Mikhail, Giuseppina Nucifora
		23 Francis street, Apt 18, Boulkely, Alexandria, Egypt

Citation

This paper should be referenced as such :

Mikhail FM, Nucifora G . FGA7 (Fused Gene 7 to AML1). Atlas Genet Cytogenet Oncol Haematol. June 2004 . URL : http://AtlasGeneticsOncology.org/Genes/FGA7ID525.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Mon Aug 11 21:13:53 2008