FGA7 (Fused Gene 7 to AML1)

2004-06-01 Fady M Mikhail , Giuseppina Nucifora Affiliation

23 Francis street, Apt 18, Boulkely, Alexandria, Egypt

Identity

HGNC

LOCATION

4q28

IMAGE

LEGEND

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.

LOCUSID

ALIAS

FGA7

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.

Proteins

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 name

t(4;21)(q28;q22) leading to RUNX1-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 patients 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.

Bibliography

Pubmed ID	Last Year	Title	Authors
14695990	2004	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 et al

Citation

Fady M Mikhail ; Giuseppina Nucifora

FGA7 (Fused Gene 7 to AML1)

Atlas Genet Cytogenet Oncol Haematol. 2004-06-01

Online version: http://atlasgeneticsoncology.org/gene/525/fga7