Translocation t(11;14)(q25;q11) associated with T-cell receptor alpha/delta gene rearrangement and ATM gene deletion in a patient with B-cell chronic lymphocytic leukaemia.
2019-12-01 Adriana Zamecnikova AffiliationKuwait Cancer Control Center, Department of Hematology, Laboratory of Cancer Genetics, Kuwait [email protected]
Previous history
Preleukaemia
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Malignant disease
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Inborn condition
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Main items
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Clinics case report
Age
40 yrs
Sex
M
Liver
-
Spleen
-
Lymph nodes
-
Cns involv
-
Blood data
Wbc
29
Hb
9.6
Platelets
117
Bone marrow
75% mature appearing lymphocytes; non-diffuse histopathological pattern.
Cyto path
Phenotype
FAB) B-cell chronic lymphocytic leukemia
Immunophenotype
CD5, CD19, CD20, CD22, CD25, CD110, CD45, HLDR, CD38 positive, with kappa light chain and sIgM expression.
Rearranged ig tcr
TRA/D+
Precise diagnosis
B-cell chronic lymphocytic leukemia
Survival data
Date diagnosis
12-2013
Treatment
None
Status
L
Date last follow
12-2013
Karyotype
Sample
t bone marrow
Culture time
24
Banding
G-banding
Results
46,XY [10]/46,XY,t(11;14)(q25;q11.2) [10]
Mol cytogenet technics
Fluoresce in situ hybridization with LSI 13q14/q34/CEP12, LSI p53/ATM, LSI MLL, LSI IGH/CCND1XT, LSI TRA/D (Abbott Molecular, Vysis,US) on interphase cells and hybridization with whole chromosome 14 probe (Metasystems, Germany) on metaphases.
Mol cytogenet results
Normal signal pattern for LSI 13q14/q34/CEP12, LSI p53, LSI MLL and LSI IGH/CCND1XT. Hybridization with LSI p53/ATM probes revealed normal signal pattern for p53 probe and in 90% of cells 1 signal for the ATM gene. Despite the B-cell lineage of leukemic cells, breakpoint at 14q11 led us to perform further FISH studies to confirm the involvement TRA/D gene in the translocation.
Indeed, hybridization with LSI TRA/D dual color break apart probe on interphase cells showed one normal fusion signal, one apparently smaller fusion signal and an additional green signal of TRA/D in 90% of cells. Subsequent FISH analyses on metaphases revealed that the 3 part of the TRA/D gene is relocated from 14q11.2 to chromosome 11 resulting in a split of TRA/D sequences (Figure 1B). Hybridization with whole chromosome 14 probe (red signal) confirmed the translocation of chromosome 14 sequences from der(14) to chromosome 11 (C). Further hybridization studies with LSI p53/ATM probe showed two normal red signals for p53 in 100 % of cells; however only one green signal of the ATM gene in 90% of cells, indicative of ATM deletion in 90% (Figure 1D).
Indeed, hybridization with LSI TRA/D dual color break apart probe on interphase cells showed one normal fusion signal, one apparently smaller fusion signal and an additional green signal of TRA/D in 90% of cells. Subsequent FISH analyses on metaphases revealed that the 3 part of the TRA/D gene is relocated from 14q11.2 to chromosome 11 resulting in a split of TRA/D sequences (Figure 1B). Hybridization with whole chromosome 14 probe (red signal) confirmed the translocation of chromosome 14 sequences from der(14) to chromosome 11 (C). Further hybridization studies with LSI p53/ATM probe showed two normal red signals for p53 in 100 % of cells; however only one green signal of the ATM gene in 90% of cells, indicative of ATM deletion in 90% (Figure 1D).
Images
FIGURE 1 Karyotype of the patient showing the translocation t(11;14)(q25;q11.2) (A). Fluorescence in situ hybridization with LSI TRA/D dual color break apart probe revealing juxtaposition of telomeric TCR sequences to chromosome 11 (B). Hybridization with whole chromosome 14 probe (Metasystems, Germany) showing one normal chromosome 14 and translocation of chromosome 14 sequences (red signal) from der(14) to chromosome 11 (C). Hybridization with LSI p53/ATM probe showing two normal red signals for p53 as well as one green signal of the ATM gene, indicative of the deletion of ATM from cells (D).
Comments section
Comments
Chromosomal rearrangements with 14q11 breakpoints are infrequent in CLL (Table 1). While available data for TRA/D involvement gene in are CLL still scarce; it is likely that TRA/D might be involved in a proportion of already published cases displaying 14q11 rearrangements. Our case confirms, that FISH analyses are necessary when TRA/D rearrangement is suggested, including cases exhibiting B-lymphoid immunophenotype. We described such a case in a patient diagnosed as having B-cell chronic lymphocytic leukemia with TRA/D rearrangment in addition to deletion of the ATM gene. The association between TRA/D rearrangement and ATM gene deletion in our patient is further supported by previous studies demonstrating that ATM is required for normal rearrangement of TRA/D, while ATM deficiency predisposes humans and mice to recurrent chromosome 14 translocations involving TRA/D (Liyanage et al.,2000; Zha et al., 2010). In conclusion, while B-cell CLL with TRA/D rearrangement is an exceedingly rare entity, our findings show that TRA/D activation may not be restricted to T-cell malignancies. The occurrence of TRA/D gene rearrangement in the absence of ATM in our patient may represent a possible distinct mechanism of oncogene activation in ATM-deficient B- lineage cells.
1. Pittman et al., 1984; 2. Yunis et al.,1984; 3. Bird et al.,1986; 4. Fleischman et al.,1989; 5. Schlegelberger et al.,1989; 6. Delhomme-Bachy et al., 1992; 7.Peterson et al., 1992; 8.Stilgenbauer et al., 1993; 9.Geisler et al., 1997; 10.Hamblin et al., 1999; 11.Wong et al., 1999; 12.Wong et al., 1999; 13. Martin-Subero et al.,2001; 14.Buhmann et al., 2002; 15. Lu et al.,2006; 16. Haferlach et al., 2007; 17.Lau et al., 2008; 18.Put et al., 2012; 19.Put et al., 2012; 20.Wawrzyniak et al., 2014; 21.Shin et al., 2015; 22.Li et al., 2016; 23.Collado et al., 2017.
| Sex/ Age | Chromosome anomalies | TRA/D status | ||
| 1. | M | 46,XY,inv(14)(q11q13)/45,idem,-12/46,XY,add(10)(q26),del(17)(p12-13) | Not done | |
| 2. | F/68 | 48,XX,+2,+12,dup(14)(q11q2?4) | Not done | |
| 3. | F/78 | 44,X,-X,add(1)(p36),add(4)(p16),del(6)(p23),add(7)(q32),i(8)(q10),-9,t(11;14)(q11;q23), del(17)(p11),del(18)(q21)/43,X,-X,add(1),add(4),del(6),add(7),t(7;14)(p13;q11),-8,-9, t(11;14)(q11;q32),del(17),del(18) | Not done | |
| 4. | M/55 | 43-46,X,-Y,del(2)(p23),del(6)(q21),del(7)(q32),del(11)(q21),-12,+t(12;17) (p11;q11),t(14;14) (q11;q32),-17,-18 | Not done | |
| 5. | M/75 | 46,XY,inv(14)(q11q32)/45,X,-Y | Not done | |
| 6. | M/57 | 46,XY,t(2;10)(q24;q24),inv(14)(q11q32)/46,XY,t(10;14)(q24;q11) | Not done | |
| 7. | M | 45,X,-Y/47,XY,+Y/48,XY,+Y,+Y/46,XY,inv(14)(q11q32) | Not done | |
| 8. | F | 46,XX,inv(14)(q11q32) | Not done | |
| 9. | M | 47,XY,t(6;14)(p12;q11),+12 | Not done | |
| 10. | M/54 | 47,XY,+12,del(14)(q11q24) | Not done | |
| 11. | F/46 | 44,X,-X,add(3)(p23),inv(6)(p25q15),-13,t(14;19)(q11;p13) | Not done | |
| 12. | M/59 | 46,XY,add(7)(p15),del(13)(q14)/46,XY,inv(14)(q11q32) | Not done | |
| 13. | M/69 | 46,XY,+8,add(9)(q11),-14,inv(14)(q11q32)/46,idem,add(13)(p11)/ 47,XY,+12 | Not done | |
| 14. | M/76 | 46,XY,del(13)(q12q21)/46,idem,del(3)(q21),der(14)t(3;14)(q21;q11) | Not done | |
| 15 | M/54 | 46,XY,del(7)(q22q32),t(10;14)(q24;q11) | Not done | |
| 16. | F | 46,XX,del(2)(q33q37)/46,XX,del(13)(q12),del(14)(q11q32),der(15)ins(15;13)(q13;q?q?), der(16)t(13;16)(q?;p11) | Not done | |
| 17. | M/56 | 47,XY,+12,t(14;18)(q32;q21)/47,idem,t(8;14)(q24;q11) | Not done | |
| 18. | F/85 | 46,XX,t(8;14)(q24;q11),?inv(9)(p21q13),del(11)(q13q23),del(13)(q14q22) | TRA/D+ | |
| 19. | M/71 | 46,XY,t(8;14)(q24;q11)/46,XY,del(13)(q14q22) | TRA/D+ | |
| 20. | F | 43-46,XX,der(4)t(4;11)(p15-16;q12),add(5)(q35),?der(8)del(8)(p21-22)add(8)(q24),der(9) t(9;17)(q34;q21),-11,-13,-14,del(14)(q11-12q24-31),der(17)del(17)(p13)del(17)(q21),inc | ||
| 21. | M62 | 47,XY,t(10;14)(q24;q11),+12 | TRA/D+ | |
| 22. | M/66 | 46,XY,t(8;14)(q24;q11),del(11)(q13q23) | Not done | |
| 23. | M | 44,XY,-6,-8,der(12;13)(q10;q10)/43,idem,-17,i(17)(q10)/44,idem,der(19) t(14;19)(q11;p13) | Not done |
Article Bibliography
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|---|---|---|---|
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| 12199774 | 2002 | CD40L stimulation enhances the ability of conventional metaphase cytogenetics to detect chromosome aberrations in B-cell chronic lymphocytic leukaemia cells. | Buhmann R et al |
| 28888994 | 2017 | Chronic lymphocytic leukemia with isochromosome 17q: An aggressive subgroup associated with TP53 mutations and complex karyotypes. | Collado R et al |
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| 2737667 | 1989 | Chromosomal characteristics of malignant lymphoma. | Fleischman EW et al |
| 9444933 | 1997 | In B-cell chronic lymphocytic leukaemia chromosome 17 abnormalities and not trisomy 12 are the single most important cytogenetic abnormalities for the prognosis: a cytogenetic and immunophenotypic study of 480 unselected newly diagnosed patients. | Geisler CH et al |
| 17805327 | 2007 | Comprehensive genetic characterization of CLL: a study on 506 cases analysed with chromosome banding analysis, interphase FISH, IgV(H) status and immunophenotyping. | Haferlach C et al |
| 10477713 | 1999 | Unmutated Ig V(H) genes are associated with a more aggressive form of chronic lymphocytic leukemia. | Hamblin TJ et al |
| 18722878 | 2008 | Occurrence of trisomy 12, t(14;18)(q32;q21), and t(8;14)(q24.1;q11.2) in a patient with B-cell chronic lymphocytic leukemia. | Lau LC et al |
| 26916070 | 2016 | The clinical significance of 8q24/MYC rearrangement in chronic lymphocytic leukemia. | Li Y et al |
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| 25284493 | 2015 | A case of CD5-positive mature B-cell neoplasm with t(10;14)(q24;q11.2) and trisomy 12. | Shin SY et al |
| 8471770 | 1993 | High frequency of monoallelic retinoblastoma gene deletion in B-cell chronic lymphoid leukemia shown by interphase cytogenetics. | Stilgenbauer S et al |
| 24138550 | 2014 | Clonal evolution in CLL patients as detected by FISH versus chromosome banding analysis, and its clinical significance. | Wawrzyniak E et al |
| 10326592 | 1999 | Cytogenetic abnormalities in chronic B-cell lymphoproliferative disorders in Chinese patients. | Wong KF et al |
| 6467179 | 1984 | Recurrent chromosomal defects are found in most patients with non-Hodgkin's-lymphoma. | Yunis JJ et al |
| 20566716 | 2010 | ATM-deficient thymic lymphoma is associated with aberrant tcrd rearrangement and gene amplification. | Zha S et al |
Citation
Adriana Zamecnikova
Translocation t(11;14)(q25;q11) associated with T-cell receptor alpha/delta gene rearrangement and ATM gene deletion in a patient with B-cell chronic lymphocytic leukaemia.
Atlas Genet Cytogenet Oncol Haematol. 2019-12-01
Online version: http://atlasgeneticsoncology.org/case-report/208898/translocation-t(11
