t(7;9)(q34;q34) TRB/NOTCH1

2003-01-01   Jacques Boyer 

1.Laboratoire d hématologie, CH du MANS, France

Clinics and Pathology

Disease

Specifically associated with T-cell Acute Lymphoblastic Leukemia (T-ALL).

Note

This translocation is related to Notch1 (TAN1) dysregulation. Mutation or chromosomal rearrangements of Notch gene have not yet been identified outside of T-ALL but Notch1 was recently studied by immunohistochemistry in various subsets of human lymphomas. Strong staining was found in Hodgkins lymphoma (HL) and anaplastic large cell lymphoma (ALCL) but much additional works is needed to determine whether Notch signaling is necessary for HL and ALCL growth and survival.

Phenotype stem cell origin

T lineage. CD4+ CD8+ double positive stage.

Epidemiology

Rare: < 1% among T-ALL.

Cytogenetics

Cytogenetics morphological

9q34 is a partner of 7q34. The other partners are 1p34, 1p32, 9q32, 10q24, 11p13, 15q22, 19p13

Additional anomalies

In T- lymphoblastic cell lines: polyploidy, inv(2)(p22;q11), inv(14)(q11;q32), del(6)(q23q27), del(4)(q13q35)

Genes Involved and Proteins

Gene name
TRB (T cell Receptor Beta)
Location
7q34
Dna rna description
The TRB locus spans 685 Kb. The locus contains 2 types of coding elements : TCR elements (64-67 variable genes TRBV, 2 clusters of diversity, joining and constant segments) and 8 trypsinogen genes. A portion of the TCRB locus has been duplicated and translocated to the chromosome 9 at 9p21.
Protein description
T cell receptor beta chains.
Gene name
NOTCH1 (Notch homolog 1, translocation-associated (Drosophila))
Location
9q34.3
Note
Notch receptors are highly conserved transmembrane glycoproteins that regulate the morphogenesis through a signaling pathway with pleiotropic effects of apoptosis, proliferation and cellular differenciation. At least one Notch homolog is expressed in human bone marrow CD34+ cells, on the basis of this finding, it is likely that members of Notch family, including TAN1, may be involved in mediating cell-fate decisions during hematopoiesis.
Dna rna description
DNA size: 49715 bases
Protein description
Size: 2256 amino acids, 272550 Da. Functions as a receptor for membrane-bound ligands Jagged1.

Result of the Chromosomal Anomaly

Description

The t(7;9) disrupts the Notch1 gene, fusing the 3¹end portion encoding its intracellular domain (ICN) to enhancer and promoter elements of the T cell receptor (TCRB). This results in overexpression of a constitutively active form of Notch activating genes that inhibit cell differenciation.The t(7;9)(q34;q34) results in a serie of tumor specific 5¹deleted Notch1 mRNA transcripts. All known beakpoints fall within a single intron in the coding sequence for the EGF repeat 34 of Notch1.
The t(7 ;9) truncated transcripts encode ICN1-like polypetides (ICN = intracellular portion of Notch receptor). These polypeptides localize to the nucleus and structurally resemble ICN1. The intracellular portion of Notch1 contains six ankyrin repeats that are similar to those found in cytoplasmic I kappa B proteins or I kappa B are specific inhibitors of nuclear factor NFKappa B transcription factors.

Oncogenesis

On primary effect of constitutive Notch 1 activation is the maturation arest of T lymphoblastes at the CD4+ CD8+ double positive stage but recent works suggest that Notch contributes to T cell transformation by influencing proliferation and survival, rather than merely blocking differenciation.

Bibliography

Pubmed IDLast YearTitleAuthors
86053271996Cytogenetic abnormalities in adult acute lymphoblastic leukemia: correlations with hematologic findings outcome. A Collaborative Study of the Group Français de Cytogénétique Hématologique.
124964712002Notch signaling in cancer.Allenspach EJ et al
110036472000Essential roles for ankyrin repeat and transactivation domains in induction of T-cell leukemia by notch1.Aster JC et al
18316921991TAN-1, the human homolog of the Drosophila notch gene, is broken by chromosomal translocations in T lymphoblastic neoplasms.Ellisen LW et al
120868902002Gene expression signatures define novel oncogenic pathways in T cell acute lymphoblastic leukemia.Ferrando AA et al
86423131996T cell leukemia-associated human Notch/translocation-associated Notch homologue has I kappa B-like activity and physically interacts with nuclear factor-kappa B proteins in T cells.Guan E et al
108057362000Neoplastic transformation by Notch requires nuclear localization.Jeffries S et al
75128371994A human homologue of the Drosophila developmental gene, Notch, is expressed in CD34+ hematopoietic precursors.Milner LA et al
13770081992Karyotype and T-cell receptor expression in T-lineage acute lymphoblastic leukemia.Secker-Walker LM et al
29626501988Clinical and biologic characterization of T-cell neoplasias with rearrangements of chromosome 7 band q34.Smith SD et al

Citation

Jacques Boyer

t(7;9)(q34;q34) TRB/NOTCH1

Atlas Genet Cytogenet Oncol Haematol. 2003-01-01

Online version: http://atlasgeneticsoncology.org/haematological/1055/t(7;9)(q34;q34)-trb-notch1

External Links