t(7;14)(p15;q32)

2017-10-01   Adriana Zamecnikova 

1.Kuwait Cancer Control Center, Department of Hematology, Laboratory of Cancer Genetics, Kuwait; annaadria@yahoo.com

Abstract

Rearrangements of T-cell receptor (TCR) genes are characteristic chromosomal abnormalities in a variety of T-cell malignancies, particularly in T-cell lymphoblastic leukemia/lymphomas, but TCR-gamma gene or TCL1A (TCR-T-cell leukemia/lymphoma 1A) rearrangements are rare.

Clinics and Pathology

Disease

T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma (T-ALL); rarely: acute myeloid leukemia (AML).

Phenotype stem cell origin

An immature thymocytic pattern: CD7-positive, surface CD3-negative and CD4/CD8- negative.

Etiology

T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma in 11 (Kaneko et al., 1989; Teramura et al., 1989; Pui et al., 1991; Toyoda et al., 1991; Heerema et al., 1998; Chang et al., 2006; Gill et al., 2011; Sugimoto et al., 2014), among them 1 with human immunodeficiency virus infection (Gill et al., 2011). Additional cases included: 1 mature T- and NK-cell neoplasm (Narayan et al., 2013), 2 AML (Raimondi et al., 1989; Strehl et al., 2001) and 1 biphenotypic leukemia ( BAL) (Xu et al., 2009).

Epidemiology

15 patients (9 males and 6 females) aged 4 to 55 years (median 14 years); mainly pediatric cases (12 out of 15 patients; aged 4 to 16 years).
Table 1. Clinical findings of patients with t(7;14)(p15;q32).
 Sex/AgeDiagnosisKaryotype
3. FAML-M246,XX,t(7;14)(p15;q32)
10. M/16AML-M446,XY,t(7;14)(p15;q32)
12. M/35BAL 46,XY,add(5)(q13),t(6;16)(q15;q24),t(7;14)(p15;q32)/92,idemx2
1. M/12T-ALL  46,XY,-6,t(7;14)(p15;q32),del(8)(q22),del(12)(p12),-13,-16,-18,+4mar
2. F/10T-ALL  46,XX,t(6;12)(q21;p13),t(7;14)(p15;q32)
5. F/4T-ALL45,XX,t(1;2)(p22;p14),t(7;14)(p15;q32),dic(12;18)(p11;p11)
6. M/14T-ALL 46, XX,t(7;14)(p15;q32)
8. MT-ALL46,XY,?inv(5)(p13q14),del(6)(p21-22),t(7;14)(p15;q32)
9. FT-ALL46,XX,del(5)(q31),del(6)(q15q23),t(7;14)(p15;q32)
11. F/7T-ALL46,XX,del(5),t(7;14)(p15;q32)/45,idem,-8,der(12)t(8;12)(q11;p11), inv(17)(p13q11)
13. M/55T-ALL46,XY,t(7;14)(p15;q32)        human immunodeficiency virus infection
15. M/22T-ALL46,XY,t(7;14)(p15;q32)        TRG/TCL1A
4. M/14T-cell lymphomat(7;14)(p15;q32)
7. M/9T-cell lymphoma46,XY,t(7;14)(p15;q32)
14. F/15MT/NKN46,XX,t(7;14)(p15;q32)/92,idemx2 

Abbreviations: AML-M2, Acute myeloblastic leukemia with maturation; AML-M4, Acute myelomonocytic leukemia; BAL, Bilineage or biphenotypic leukemia; T-ALL, T-Acute lymphoblastic leukemia/lymphoblastic lymphoma; MT/NKN, Mature T- and NK-cell neoplasm.
1-2. Kaneko et al., 1989; 3. Raimondi et al., 1989; 4. Teramura et al., 1989; 5-6. Pui et al., 1991; 7. Toyoda et al., 1991; 8-9. Heerema et al., 1998; 10.Strehl et al., 2001; 11. Chang et al., 2006; 12. Xu et al., 2009; 13. Gill et al., 2011; 14. Narayan et al., 2013; 15. Sugimoto et al., 2014.

Prognosis

6 of the described patients achieved clinical remission after therapy and had a favorable outcome with survival of 1 to 24+ months (Data from Sugimoto et al., 2014).

Cytogenetics

Note

Because precise breakpoints are often difficult to define, it is possible that the reported t(7;14)(p15;q32) involve various 7p14-7p15.1-p15.3 breakpoints and dispersion of breakpoints throughout the 14q32.1-32.3 region involving various genes.

Cytogenetics morphological

Sole anomaly in 6 T-Acute lymphoblastic leukemia/lymphoblastic lymphoma (Teramura et al., 1989; Pui et al., 1991; Toyoda et al., 1991; Gill et al., 2011; Narayan et al., 2013; Sugimoto et al., 2014) and in both AML patients (Raimondi et al., 1989; Strehl et al., 2001); found in association with 5q deletion in 1 (Heerema et al., 1998) and 12p anomalies in 4 (Kaneko et al., 1989; Pui et al., 1991; Chang et al., 2006).

Genes Involved and Proteins

Gene name
TRG (T-cell receptor gamma)
Location
7p14.1
Note
Belongs to the family of T-cell receptor genes encoding T-cell receptor gamma chains, previously often described as located at band 7p14-p15. Note that the breakpoint has been described at 7p15 in a case with TRG+ (Sugimoto et al., 2014).
Gene name
TCL1A (T-cell leukemia/lymphoma 1A)
Location
14q32.1
Protein description
HOXA cluster genes at 7p15 act as transcription factors regulating gene expression, morphogenesis, and differentiation. Chromosomal disruption of HOXA genes by chromosomal rearrangements such as inv(7)(p15q34) or t(7;7)(p15;q34) that involve TRB at 7q34 and t(7;14)(p15;q11) that disrupt TRD at 14q11 results in HOXA upregulation and ectopic expression in T-cell acute lymphoblastic leukemia/lymphoma, indicating important role for HOXA genes in T-ALL.TCL1A located on 14q32.1 and TCL1B located centromeric of TCL1A belong to the TCL1 family of genes known to be affected by chromosomal rearrangements in T-cell leukemia/lymphoma. TCL1 is a target of chromosomal translocations t(14;14)(q11;q32.1) or t(7;14)(q35;q32.1) and inversions inv(14)(q11q32.1) involving the T- cell receptor alpha /delta locus at 14q11 and TCR beta loci at 14q35 leading to its deregulation in T-cell leukemias, such as T-prolymphocytic leukemia. It is also activated in preleukemic clonal cells and chronic leukemias arising in cases of immunodeficiency syndromes such as ataxia-telangiectasia as a consequence of chromosome translocation involving TRA/TRD locus. TCL1 functions as a coactivator in a PI3-kinase dependent Akt pro-survival pathway.

Result of the Chromosomal Anomaly

Oncogenesis

The chromosomal translocation t(7;14)(p15;q32) is associated with T-cell acute leukemia/lymphoma mainly, indicating the abnormality may involve genes casually implicated in the development of these types of malignancies. Found often as a sole anomaly or in association with limited additional rearrangements in the majority of reported patients, thus probably involved in the initiation of malignancy. The fusion of TCL1A/TCL1B and TRG genes was confirmed by FISH in 1 patient (Sugimoto et al., 2014), indicating that activation of TCL1 by its juxtaposition to regulatory elements of T-cell receptor gene leading to TCL1 overexpression is involved in leukemogenesis. However, in the remaining patients the genes involved are unknown and probable various genes have been implicated. It is possible that in some patients, the abnormality may involve other genes such as HOXA genes identified in 7p15 region and TCL1B (TML1) and TCL6 (TNG1, or TNG2) that are overexpressed in T-cell leukemias with 14q32.1 rearrangements.

Bibliography

Pubmed IDLast YearTitleAuthors
168492812006Cytogenetics in childhood acute lymphoblastic leukemia in Taiwan: a single-institutional experience.Chang HH et al
95520251998Frequency and clinical significance of cytogenetic abnormalities in pediatric T-lineage acute lymphoblastic leukemia: a report from the Children's Cancer Group.Heerema NA et al
25861831989Chromosomal and immunophenotypic patterns in T cell acute lymphoblastic leukemia (T ALL) and lymphoblastic lymphoma (LBL).Kaneko Y et al
239297562013PCDH10 promoter hypermethylation is frequent in most histologic subtypes of mature lymphoid malignancies and occurs early in lymphomagenesis.Narayan G et al
18785941991Characterization of childhood acute leukemia with multiple myeloid and lymphoid markers at diagnosis and at relapse.Pui CH et al
27583951989Cytogenetics of childhood acute nonlymphocytic leukemia.Raimondi SC et al
111575012001Multiplex reverse transcriptase-polymerase chain reaction screening in childhood acute myeloblastic leukemia.Strehl S et al
249669762014T-cell lymphoblastic leukemia/lymphoma with t(7;14)(p15;q32) [TCRγ-TCL1A translocation]: a case report and a review of the literature.Sugimoto KJ et al
17092161991[CD5+, CD7+, and CD19+ non-Hodgkin's lymphoma in a child].Toyoda Y et al
194544972009Clinical and biological characteristics of adult biphenotypic acute leukemia in comparison with that of acute myeloid leukemia and acute lymphoblastic leukemia: a case series of a Chinese population.Xu XQ et al

Summary

Fusion gene

TCL1A/HOX1@

Fusion gene

TCL1A/TRG

Citation

Adriana Zamecnikova

t(7;14)(p15;q32)

Atlas Genet Cytogenet Oncol Haematol. 2017-10-01

Online version: http://atlasgeneticsoncology.org/haematological/1059/t(7;14)(p15;q32)