t(6;7)(q23;q34) TRB/MYB and AHI1

2007-07-01   Jean Soulier , Emmanuelle Clappier 

1.Group Genome Rearrangements, Cancer, Hematology Laboratory APHP, INSERM U728, Paris 7 University, Institut Universitaire d_Hématologie, Hôpital Saint-Louis, Paris, France
2.Group Genome Rearrangements, Cancer, Hematology Laboratory APHP, INSERM U728, Paris 7 University, Institut Universitaire d_Hématologie, Hôpital Saint-Louis, Paris, France

Clinics and Pathology

Phenotype stem cell origin

T cell precursor.

Epidemiology

Less than 5% among a series of non selected adult and pediatric T-ALLs (n = 3 out of 92). Six cases were described, all of them children, and 5 out of 6 being under 3 years old (1.1, 1.3, 1.8, 2.5, and 2.9 years old, respectively), which is very young for T-cell leukemia. The t(6;7) translocation could therefore be relatively common in this very low range of age.

Cytology

Lymphoblasts

Prognosis

The prognosis is yet to be evaluated.

Cytogenetics

Atlas Image
Left: Whole chromosome painting of chromosomes 6 (green) and 7 (red). Right: Locus-specific break-apart FISH using 6q23 probes RP11-184J4 (red) and RP11-845K5 (green) showing translocation involving the 6q23 locus.

Cytogenetics morphological

t(6;7)(q23;q34) may be barely detectable by chromosome banding techniques alone.

Cytogenetics molecular

Involvement of the TCRB locus and the MYB locus can be demonstrated using flanking FISH probes.

Genes Involved and Proteins

Gene name
TRB (T cell Receptor Beta)
Location
7q34
Protein description
T-cell receptor beta chain
Gene name
MYB (v-myb myeloblastosis viral oncogene homolog (avian))
Location
6q23.3
Dna rna description
Spans over 38 kb, 15 exons (and additionnal alternative exons), mRNA 3.3 kb.
Protein description
v-myb myeloblastosis viral oncogene homolog. Transcription factor. 640 amino acids.
Gene name
AHI1 (Abelson helper integration site 1)
Location
6q23.3
Dna rna description
Spans over 214 kb, 28 exons (and additional alternative exons), mRNA 5.5 kb.
Protein description
Jouberin (Abelson helper integration site 1 protein homolog) (AHI-1). 1196 amino acids including one SH3 domain and WD repeats.

Result of the Chromosomal Anomaly

Note

No fusion gene
The t(6;7)(q23.3;q34) translocation results in juxtaposition of TRB regulatory sequences to the MYB-AHI1 locus. It results in deregulated expression of C-MYB, as demonstrated by skewed allelic expression.

Oncogenesis

C-MYB is a transcription factor involved in hematopoiesis. In T-cell differenciation, discrete threshold levels of MYB activity regulate transition through distinct stages, suggesting that a deregulated expression could disturb the maturation process and play a role in oncogenesis.
A potential role of AHI1 deregulation as a cofactor has to be evaluated.
Of note, the same locus at 6q23.3 is also involved in short tandem duplications of a about 230 kb genomic region which includes the C-MYB gene (about 10% T-ALL in children and adults). This somatic abnormality can be detected by array-CGH, genomic Q-PCR or fiber-FISH, but not or hardly by standard metaphasic or interphasic FISH.

Bibliography

Pubmed IDLast YearTitleAuthors
174525172007The C-MYB locus is involved in chromosomal translocation and genomic duplications in human T-cell acute leukemia (T-ALL), the translocation defining a new T-ALL subtype in very young children.Clappier E et al
174357592007Duplication of the MYB oncogene in T cell acute lymphoblastic leukemia.Lahortiga I et al
159213752005Analysis of balanced rearrangements of chromosome 6 in acute leukemia: clustered breakpoints in q22-q23 and possible involvement of c-MYB in a new recurrent translocation, t(6;7)(q23;q32 through 36).Sinclair P et al

Summary

Atlas Image
R-band analysis. Partial karyotype showing t(6;7)(q23;q34)

Citation

Jean Soulier ; Emmanuelle Clappier

t(6;7)(q23;q34) TRB/MYB and AHI1

Atlas Genet Cytogenet Oncol Haematol. 2007-07-01

Online version: http://atlasgeneticsoncology.org/haematological/1465/t(6;7)(q23;q34)-trb-myb-and-ahi1

External Links