t(1;7)(p34;q34)

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Home Genes Leukemias Solid Tumours Cancer-Prone Deep Insight Case Reports Journals Portal Teaching

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

t(1;7)(p34;q34)

Clinics and Pathology

Disease Specifically associated with T-cell Acute Lymphoblastic Leukemia (T-ALL). This translocation is related to LCK dysregulation.

Phenotype / cell stem origin T lineage.

Epidemiology Rare : < 1% among T-ALL

Cytogenetics

Cytogenetics Morphological 1p34 is a partner of 7q34. The other partners of 7q34 are 1p32, 9q32, 9q34, 10q24, 11p13, 15q22, 19p13. 22q13 is a novel partner of 1p34 in a precursor T-lymphoblastic leukemia.

Genes involved and Proteins

Gene Name TCRB : T-cell receptor beta-chain gene.

Location 7q35

Dna / Rna The TRB locus at 7q35 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 T cell receptor beta chains.

Gene Name LCK (lymphocyte-specific tyrosine kinase gene)

Location 1p34

Dna / Rna The LCK gene encodes a lymphocyte-specific member of the Src family of protein kinases. Size and orientation strand are unknown. This gene is assigned to bands 1p34.3 by fluorescence in situ hybridation and its mapping relative to the reference marker pYNZ2 (D1S57).
LCK is normally expressed from two distinct promoters.
A proximal promoter initiates transcripts designated as type I.
A distal promoter, found approximately 30 kb further upstream, initiates transcripts designated as type II.
Human thymocytes and all the leukemic T cell lines express both type I and type II LCK transcripts, albeit at different levels. Peripheral blood mature T cell express mainly type II LCK transcripts.
The two types of human LCK transcripts are distingued by their 5'-untranslated regions. However, the protein kinase encoded by both transcripts is the same.

Protein The human lymphocyte specific protein tyrosine kinase is a 57869kDa protein (p56LCK) 508 amino acids, involved in T-cell and IL2-receptor signaling important for antigen-induced T-cell activation.

Result of the chromosomal anomaly

Hybrid gene
Description The T-cell acute lymphoblastic leukemia cell line HSB-2 has the t(1;7)(p34;q34) translocation. The T-cell acute lymphoblastic leukemia cell line SUP-T12 has the same translocation.
The breakpoint in the HSB-2 cell line at 1p34 occurs between the type I and type II promoters and thus separates the two LCK promoters and the type II promoter is translocated to the der(7) chromosome. The breakpoint in the SUP-T12 at 1p34 occurs 2kb upstream of the type II promoter, leaving an intact LCK gene on the der(1) chromosome.
In HSB-2 the t(1;7) fuses the TCRB constant region and transcriptionnal enhancer with the type I transcription unit of LCK on the der(1) chromosome. (the type II promoter is translocated to the der(7) chromosome). Thus the TCRB enhancer upregulates the type I trancripts.
An independent t(1;7) in SUP-T12 also resulted in the juxtaposition of LCK to TCRB. The p56LCK protein is elevated approximately 2-fold in comparaison with that in normal T-cell lines and total cellular tyrosine phosphorylation is elevated approximately 10-fold.

Fusion Protein
Note No fusion protein.

Oncogenesis The oncogenic p56LCK in T-cell-leukemia lines contains an amino acid substitution within the CD4/CD8 binding domain, two substitutions in the kinase domain and an insertion between the SH2 and kinase domains. These mutations of LCK and the overexpression of p56LCK protein may contribute to some human T-cell leukemias.

External links

Other database t(1;7)(p34;q34) Mitelman database (CGAP - NCBI)

Other database t(1;7)(p34;q34) CancerChromosomes (NCBI)

Other database	t(1;7)(p34;q34)	Mitelman database (CGAP - NCBI)
Other database	t(1;7)(p34;q34)	CancerChromosomes (NCBI)

Bibliography

The LCK gene is involved in the t(1;7)(p34;q34) in the T-cell acute lymphoblastic leukemia derived cell line, HSB-2.

Burnett RC, David JC, Harden AM, Le Beau MM, Rowley JD, Diaz MO

Genes, chromosomes & cancer. 1991 ; 3 (6) : 461-467.

PMID 1663780

Karyotype and T-cell receptor expression in T-lineage acute lymphoblastic leukemia.

Secker-Walker LM, Campana D, Hawkins JM, Sampson RE, Coustan-Smith E

Genes, chromosomes & cancer. 1992 ; 4 (1) : 41-45.

PMID 1377008

Molecular analysis of the T-cell acute lymphoblastic leukemia-associated t(1;7)(p34;q34) that fuses LCK and TCRB.

Burnett RC, Thirman MJ, Rowley JD, Diaz MO

Blood. 1994 ; 84 (4) : 1232-1236.

PMID 8049439

Cytogenetic abnormalities in adult acute lymphoblastic leukemia: correlations with hematologic findings outcome. A Collaborative Study of the Group Franˆßais de Cytogˆ©nˆ©tique Hˆ©matologique.

Blood. 1996 ; 87 (8) : 3135-3142.

PMID 8605327

Gene expression signatures define novel oncogenic pathways in T cell acute lymphoblastic leukemia.

Ferrando AA, Neuberg DS, Staunton J, Loh ML, Huard C, Raimondi SC, Behm FG, Pui CH, Downing JR, Gilliland DG, Lander ES, Golub TR, Look AT

Cancer cell. 2002 ; 1 (1) : 75-87.

PMID 12086890

Contributor(s)

Written 08-2003 Jacques Boyer

Citation

This paper should be referenced as such :
Boyer J . t(1;7)(p34;q34). Atlas Genet Cytogenet Oncol Haematol. August 2003 .
URL : http://AtlasGeneticsOncology.org/Anomalies/t0107p34q34ID1045.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Mon May 12 18:11:52 2008

Home Genes Leukemias Solid Tumours Cancer-Prone Deep Insight Case Reports Journals Portal Teaching

For comments and suggestions or contributions, please contact us

j.l.huret@chu-poitiers.fr.

Disease	Specifically associated with T-cell Acute Lymphoblastic Leukemia (T-ALL). This translocation is related to LCK dysregulation.
Phenotype / cell stem origin	T lineage.
Epidemiology	Rare : < 1% among T-ALL

Gene Name	TCRB : T-cell receptor beta-chain gene.
Location	7q35
Dna / Rna	The TRB locus at 7q35 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	T cell receptor beta chains.

Gene Name	LCK (lymphocyte-specific tyrosine kinase gene)
Location	1p34
Dna / Rna	The LCK gene encodes a lymphocyte-specific member of the Src family of protein kinases. Size and orientation strand are unknown. This gene is assigned to bands 1p34.3 by fluorescence in situ hybridation and its mapping relative to the reference marker pYNZ2 (D1S57). LCK is normally expressed from two distinct promoters. A proximal promoter initiates transcripts designated as type I. A distal promoter, found approximately 30 kb further upstream, initiates transcripts designated as type II. Human thymocytes and all the leukemic T cell lines express both type I and type II LCK transcripts, albeit at different levels. Peripheral blood mature T cell express mainly type II LCK transcripts. The two types of human LCK transcripts are distingued by their 5'-untranslated regions. However, the protein kinase encoded by both transcripts is the same.
Protein	The human lymphocyte specific protein tyrosine kinase is a 57869kDa protein (p56LCK) 508 amino acids, involved in T-cell and IL2-receptor signaling important for antigen-induced T-cell activation.

Note	No fusion protein.
Oncogenesis	The oncogenic p56LCK in T-cell-leukemia lines contains an amino acid substitution within the CD4/CD8 binding domain, two substitutions in the kinase domain and an insertion between the SH2 and kinase domains. These mutations of LCK and the overexpression of p56LCK protein may contribute to some human T-cell leukemias.