t(3;9)(p13;q34.1) FOXP1/ABL1

2016-09-01   Julie Sanford Biggerstaff 

1.Idaho Cytogenetics Diagnostic Laboratory, Boise, ID 83706/ biggersj@slhs.org

Abstract

Review on t(3;9)(p13;q34.1) FOXP1/ABL1, with data on clinics, and the genes involved.

Clinics and Pathology

Disease

Pre-B Cell Acute Lymphoblastic Leukemia/Lymphoma (ALL) and Follicular Lymphoma (Ernst et al., 2011; Koduru et al., 1997).

Note

The FOXP1/ABL1 involvement was ascertained only in the B-ALL case. t(3;9) was found in a sub-clone and against the background of a complex karyotype and TP53 gene mutation in the follicular lymphoma case.

Phenotype stem cell origin

Pre-B cell.

Epidemiology

1 ALL case reported to date: a 16 yo female patient, and 1 follicular lymphoma case reported to date: a 52 yo male patient.

Cytology

High leukocytosis (>50,000 x 109/L) at diagnosis.

Treatment

For ALL: Standard COALL (German Cooperative Study Group) protocol for high-risk ALL followed by Allogeneic BMT; may be sensitive to treatment with first or 2nd generation tyrosine kinase inhibitors.

Prognosis

Yet unknown; ALL patient was reported in remission 9 years post diagnosis, but after paternal origin haplo-identical BMT.

Genes Involved and Proteins

Gene name
FOXP1 (Forkhead box P1)
Location
3p13
Note
Member of forkhead box (FOX) subfamily P; transcription factor. These proteins play a role in cell- and tissue-specific gene transcription regulation.
Dna rna description
Gene is 176,228 bp with 16 exons; transcribed from the - strand ; coding region is 171,437 bp with 14 exons.
Protein description
At least 12 protein isoforms produced; dimerizes with FOXP2 and FOXP4 using the leucine-zipper domain which is required for DNA binding capability. Protein locates to the nucleus.
Germinal mutations
Germline mutations of FOXP1 are associated with autosomal dominant intellectual disability with language impairment, with or without autistic features (MIM phenotype 613670).
Gene name
ABL1 (v-abl Abelson murine leukemia viral oncogene homolog 1)
Location
9q34.12
Dna rna description
Expressed as either 6- or 7-Kb transcript.
Protein description
Tyrosine kinase; located in either the nucleus (shorter transcript) or cytoplasm (longer transcript) depending on which splice variant is produced (Chissoe et al., 1995).

Result of the Chromosomal Anomaly

Note

In the single patient characterized, the in-frame fusion was confirmed between FOXP1 exon 19 (ENST00000318789) and ABL1 exon 4 (ENST00000318560) (Ernst et al., 2011).

Description

ABL1 exon 4 fused with FOXP1 alternative RNA isoform (NM_032682).

Detection protocole

RT-PCR

Bibliography

Pubmed IDLast YearTitleAuthors
76651851995Sequence and analysis of the human ABL gene, the BCR gene, and regions involved in the Philadelphia chromosomal translocation.Chissoe SL et al
213919722011Identification of FOXP1 and SNX2 as novel ABL1 fusion partners in acute lymphoblastic leukaemia.Ernst T et al
209507882010De novo mutations in FOXP1 in cases with intellectual disability, autism, and language impairment.Hamdan FF et al
93546781997Correlation between mutation in P53, p53 expression, cytogenetics, histologic type, and survival in patients with B-cell non-Hodgkin's lymphoma.Koduru PR et al

Summary

Fusion gene

FOXP1/ABL1

Citation

Julie Sanford Biggerstaff

t(3;9)(p13;q34.1) FOXP1/ABL1

Atlas Genet Cytogenet Oncol Haematol. 2016-09-01

Online version: http://atlasgeneticsoncology.org/haematological/1619/t(3;9)(p13;q34-1)

External Links