+X solely in lymphomas

2017-07-01   Adriana Zamecnikova  

1.Kuwait Cancer Control Center, Department of Hematology, Laboratory of Cancer Genetics, Kuwait; [email protected]

Abstract

Review on +X solely in lymphomas, with data on clinics.

Clinics and Pathology

Disease

B- and T-cell lymphomas and chronic lymhocytic leukemia (CLL).

Phenotype stem cell origin

39 lymphoma cases to date; among them, lymphomas with B-cell phenotype in 26 patients: follicular lymphoma (FL, n=6) (Rosenwald et al 1999; Horsman et al 2001; Goodlad et al 2003; Fan & Rizkalla 2003; Rajgopal et al 2003; Aamot et al 2007), diffuse large B-cell lymphomas (DLBCL, n=6) (Koduru et al., 1987; Konishi et al., 1990; Cigudosa et al., 1999; Cerretini et al., 2006; Niitsu et al., 2009; Niitsu et al., 2009); mature B-cell neoplasm (n=3, MBCN) ( Maseki et al., 1987; Coignet et al., 1996; Cook et al., 2004), nodal marginal zone B-cell lymphoma (NMZL, n=3) ( Cook et al., 2004; Aamot et al., 2005; Martin-Subero et al., 2007); splenic marginal zone B-cell lymphoma (SMZL, n=3) (Dierlamm et al., 1996; Le Baccon et al., 2001; Narayan et al., 2013), Hodgkin disease (HD, n=3) (Dennis et al., 1989; Schlegelberger et al., 1994; Falzetti et al., 1999), 1 post-transplant lymphoproliferative disorder with primary non-Hodgkin lymphoma (Djokic et al., 2006) and 1 mantle cell lymphoma case (Siebert et al., 1998). Various T-cell malignancies in 13 patients: most often angioimmunoblastic T-cell lymphoma (ATCL, n=6) (Godde-Salz et al., 1987; Kaneko et al., 1988; Schlegelberger et al., 1990), mature T- and NK-cell neoplasm (n=2) (Hashimoto et al., 1995), mycosis fungoides/Sezary syndrome (n=2) (van Vloten et al., 1979; Limon et al., 1995), adult T-cell lymphoma/leukemia (HTLV-1+) (ATL, n=2) (Sanada et al., 1986; Itoyama et al., 2001) and 1 there was 1 unspecified peripheral T-cell lymphoma case (Schlegelberger et al., 1994) (Table 1).
 B>Sex/AgeB>DiseaseB>Karyotype
1 F/75$Mycosis fungoides/Sezary syndrome 46,XX,dmin/47,XX,+X
2 F/62Adult T-cell lymphoma/leukemia (HTLV-1+)46,XX,add(2)(p13),del(3)(q2?1q2?5)/45,X,-X/47,XX,+X
3 M/75Angioimmunoblastic T-cell lymphoma 47,XY,+X/47,idem,del(10)(p12)          LN
4 F/64Angioimmunoblastic T-cell lymphoma  47,XX,+X          LN
5 F/73Diffuse large B-cell lymphoma47,XX,+X          LN
6 M/82Mature B-cell neoplasm, NOS47,XY,+X          LN
7 F/63Angioimmunoblastic T-cell lymphoma47,XX,+add(3)(p11)/47,XX,+X          LN
8 M/49Hodgkin disease, NOS47,XY,+X          LN
9 M/72Diffuse large B-cell lymphoma 47,XY,+X          LN
10 F/63Angioimmunoblastic T-cell lymphoma49,XX,+5,+19,+21/47,XX,+X/46,XX,inv(14)(q11q32)/45,X,-X          LN
11 F/78Angioimmunoblastic T-cell lymphoma47,XX,+X          LN
12 F/47Angioimmunoblastic T-cell lymphoma47,XX,+X          LN
13 F/35Hodgkin disease, nodular sclerosis78-82,XX,-X,-X,i(1)(q10),add(5)(p?),del(6)(q?)x2,add(7)(q?),del(7) (q?),del (9)(p?),hsr(11)(p?),add(19)(q?),+mar/47,XX,+X          LN
14 F/65Peripheral T-cell lymphoma, unspecified47,XX,+X
15 M/54Mature T- and NK-cell neoplasm, NOS 47,XY,+X/35-42,XY,der(1;13)(q10;q10),der(1;14)(p10;q10)          LN
16 M/78Mature T- and NK-cell neoplasm, NOS47,XY,+X          LN
17 F/64Mycosis fungoides/Sezary syndrome 43-45,XX,del(3)(p11),i(6)(p10),+8,add(10)(q24),del(12)(p11),der(17)t(3;17) (q12;p11),add(19)(q13),+mar,inc/47,XX,+X/41-44,XX,+7,inc
18 F/89Mature B-cell neoplasm, NOS47,XX,+12/47,XX,+X          LN
19 F/57Splenic marginal zone B-cell lymphoma47,XX,+X          LN
20 F/60Mantle cell lymphoma80-88,XXXX,+X,add(1)(q32),del(1)(q24),-4,-6,del(6)(q21q23),-9,-9,t(11;14) (q13;q32),add(12)(q24),-13,-13,der(14)t(11;14),-15,-15,+16, -19,-22,+3mar/47, XX,+X LN
21 FDiffuse large B-cell lymphoma47,XX,+X          LN
22  F/16Hodgkin disease, nodular sclerosis 47,XX,+X          LN
23 FFollicular lymphoma47,XX,+X           LN
24 F/73Splenic marginal zone B-cell lymphoma46,XX,dup(1)(?q12?q31),del(7)(q32q36)/47,XX,+X          LN
25 F/32Adult T-cell lymphoma/leukemia (HTLV-1+) 47,XX,+X/49,XX,+del(3)(p13),+5,+11
26 M/51Follicular lymphoma47,XY,+X/49,idem,t(14;18)(q32;q21),+i(18)(q10),+21          LN
27 F/62Follicular lymphoma51,XX,+X,+3,del(4)(q31),add(10)(p13),t(14;18)(q32;q21),+18,+21, +r/52,idem, +2/51,idem,add(2)(p23)/47,XX,+X          LN
28 MFollicular lymphoma47,XY,+X/47-49,idem,+7,t(9;10)(p10;q10),t(14;18)(q32;q21),+21 LN
29 M/51Follicular lymphoma47,XX,+X/49-52,XY,+X,+2,+12,t(14;18)(q32;q21),+21,+mar          LN
30 FNodal marginal zone B-cell lymphoma48,XX,+3,del(11)(q23),del(13)(q12q14),+18/47,XX,+X          LN
31 MMature B-cell neoplasm, NOS 47,XY,+X/50,idem,+X,add(1)(p36),trp(1)(q21q32),+add(2)(p23),+der(3;4)(p10;q10),add(6)(p25),+12,der(14;15)(p10;q10)add(14)(q32),+18,i(21)(q10),add(22)(p11),+mar          LN
32 F/75Nodal marginal zone B-cell lymphoma47,XX,+X          LN
33 M/36Diffuse large B-cell lymphoma47,XY,+X
34 F/40Post-transplant lymphoproliferative disorder 47,XX,+X          primary non-Hodgkin lymphoma
35 MFollicular lymphoma 47,XY,+X/47,idem,der(1)add(1)(p36)t(1;6)(q32;q13),der(6)t(1;6),del(13)(q31), t(14;18)(q32;q21)          LN
36 F/85Nodal marginal zone B-cell lymphoma46,XX,del(1)(q42-43),der(7)t(3;7)(q21;q34-35)/48,idem,del(X)(q23-24),der(3)ins(3;7)(q?24;?),+der(3)t(3;7)(p25;?),t(14;19) (q32;q13),+mar/47,XX,+X          LN
37 M/54Diffuse large B-cell lymphoma55,XY,+X,+2,+3,t(8;14)(q24;q32),t(14;18)(q32;q21)/47,XY,+X          LN
38 F/44Diffuse large B-cell lymphoma 47,XX,+X,t(8;14)(q24;q32),t(14;18)(q32;q21)/47,XX,+X           LN
39 M/50Splenic marginal zone B-cell lymphoma47,XY,+X          LN

B>Abbreviations: M, male; F, female; LN, lymph node.
1.van Vloten et al., 1979; 2. Sanada et al., 1986; 3-4. Godde-Salz et al., 1987; 5. Koduru et al., 1987; 6. Maseki et al., 1987; 7. Kaneko et al., 1988; 8. Dennis et al., 1989; 9. Konishi et al., 1990; 10-12. Schlegelberger et al., 1990; 13-14. Schlegelberger et al., 1994; 15-16. Hashimoto et al., 1995; 17. Limon et al., 1995; 18. Coignet et al., 1996; 19. Dierlamm et al., 1996; 20. Siebert et al., 1998; 21. Cigudosa et al., 1999; 22.  Falzetti et al., 1999; 23. Rosenwald et al., 1999; 24. Le Baccon et al., 2001; 25. Itoyama et al., 2001; 26. Horsman et al., 2001; 27 Goodlad et al., 2003; 28. Fan & Rizkalla., 2003; 29. Rajgopal et al., 2003; 30-31. Cook et al., 2004; 32. Aamot et al., 2005; 33. Cerretini et al., 2006; 34. Djokic et al., 2006; 35. Aamot et al., 2007; 36. Martin-Subero et al., 2007; 37-38. Niitsu et al., 2009; 39. Narayan et al., 2013.
Chronic lymphocytic leukemia was found in 16 patients (Barbieri et al., 1984; Ohtaki et al., 1986; Asou et al., 1994; Arif et al., 1995; Mould et al., 1996; Geisler et al., 1997; Lopez et al., 2012) (Table 2).

 Sex/AgeKaryotype
1 F/4047,XX,+X
2 F/5947,XX,+12/47,XX,+8/47,XX,+16/47,XX,+17/47,XX,+18/47,XX,+X/46,XX,del(6)(q?)/46,XX,del(10)(q?)
3 F47,XX,+X
4 F/7947,XX,+X/46,XX,-1,+15
5 F47,XX,+12/47,idem,del(13)(q12q14)/47,XX,+X
6 F47,XX,+X
7 F47,XX,+X
8 F45,X,-X/47,XX,+X
9 F46,XX,del(6)(q15q22)/47,XX,+X
10 F47,XX,+X
11 M47,XY,+X
12 F47,XX,+X,inv(9)(p13q12)c
13 M47,XY,+X
14 M45,XY,der(8;17)(q10;q10)/46-47,XY,+X
15 F47,XX,+X
16 F47,XX,+12/47,XX,+X

Figure 2. Clinical and karyotyping data in chronic lymphocytic leukemia patients.
1. Barbieri et al., 1984; 2. Ohtaki et al., 1986; 3. Asou et al., 1994; 4. Arif et al., 1995; 5. Mould et al., 1996; 6-15. Geisler et al., 1997 16. Lopez et al., 2012.

Epidemiology

14 males and 25 females with various forms of lymphomas (aged 16 to 89 years; median age 62 years); median age was 62 years in B-cell lymphomas (11 males and 15 females aged 16 to 89 years); female prevalence in T-cell malignancies (3 males, 10 females aged 32 to 78 years). Similarly, there is a female prevalence in chronic lymphocytic leukemia patients (3 males and 13 females), aged 40 to 79 years (from the known data).

Prognosis

Unknown, due to the heterogeneity of diseases; (indolent versus aggressive disease); patients with only numerical abnormalities may have better outcome than patients with structural changes in a sideline.

Cytogenetics

Atlas Image
Figure 1. Partial karyotype showing an extra copy of chromosome X (A). Fluorescence in situ hybridization with centromeric CEP X/Y probe (Abbott Molecular, Vysis, US) showing 3 copies of chromosome X (red signal) in metaphase and interphase cells (B).

Genes Involved and Proteins

Note
Whole chromosome gain of an X chromosome has been described in various types of hematological malignancies, including malignant lymphomas. Additional sex chromosomes are usually part of complex karyotypes, representing secondary karyotypic alterations in a significant proportion of lymphomas, and less frequently in CLL. While extra X chromosome is a known numerical abnormality in these diseases, its gain as the sole acquired abnormality is not a common feature. Numerical X chromosome changes are often found in a sideline, indicative of a multistep pathogenesis, where X chromosome gain would likely represent a relatively early genetic event. However, it is unclear whether +X alone is capable of promoting oncogenesis or aberrant effects of the trisomy might allow direct acquisition of cancer-promoting mutations.

Article Bibliography

Pubmed IDLast YearTitleAuthors
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172355512007Non-Hodgkin lymphoma with t(14;18): clonal evolution patterns and cytogenetic-pathologic-clinical correlations.Aamot HV et al
74752691995Independent clones of trisomy 12 and retinoblastoma gene deletion in Japanese B cell chronic lymphocytic leukemia, detected by fluorescence in situ hybridization.Arif M et al
81362711993Japanese B cell chronic lymphocytic leukaemia: a cytogenetic and molecular biological study.Asou H et al
64326401984Cytogenetic evaluation of bone marrow involvement in non-Hodgkin's lymphomas. A survey of 94 cases.Barbieri D et al
165196992006New chromosome abnormalities and lack of BCL-6 gene rearrangements in Argentinean diffuse large B-cell lymphomas.Cerretini R et al
103379961999Cytogenetic analysis of 363 consecutively ascertained diffuse large B-cell lymphomas.Cigudosa JC et al
86676441996Automated counting of in situ hybridization dots in interphase cells of leukemia samples.Coignet LJ et al
151983542004Utility of routine classical cytogenetic studies in the evaluation of suspected lymphomas: results of 279 consecutive lymph node/extranodal tissue biopsies.Cook JR et al
27026191989Cytogenetic studies of Hodgkin's disease. Analysis of involved lymph nodes from 12 patients.Dennis TR et al
85476551996Marginal zone B-cell lymphomas of different sites share similar cytogenetic and morphologic features.Dierlamm J et al
162836192006Post-transplant lymphoproliferative disorder subtypes correlate with different recurring chromosomal abnormalities.Djokic M et al
101909421999Genomic instability and recurrent breakpoints are main cytogenetic findings in Hodgkin's disease.Falzetti D et al
127421582003Comprehensive cytogenetic analysis including multicolor spectral karyotyping and interphase fluorescence in situ hybridization in lymphoma diagnosis. a summary of 154 cases.Fan YS et al
38211571987Chromosomal abnormalities in lymphogranulomatosis X (LgrX)/angioimmunoblastic lymphadenopathy (AILD).Gödde-Salz E et al
94449331997In 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
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77739611995Correlations of chromosome abnormalities with histologic and immunologic characteristics in 49 patients from Akita, Japan with non-Hodgkin lymphoma.Hashimoto K et al
112417902001Analysis of secondary chromosomal alterations in 165 cases of follicular lymphoma with t(14;18).Horsman DE et al
113696582001Cytogenetic analysis and clinical significance in adult T-cell leukemia/lymphoma: a study of 50 cases from the human T-cell leukemia virus type-1 endemic area, Nagasaki.Itoyama T et al
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226190942012Different distribution of NOTCH1 mutations in chronic lymphocytic leukemia with isolated trisomy 12 or associated with other chromosomal alterations.López C et al
115794652001Novel evidence of a role for chromosome 1 pericentric heterochromatin in the pathogenesis of B-cell lymphoma and multiple myeloma.Le Baccon P et al
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239297562013PCDH10 promoter hypermethylation is frequent in most histologic subtypes of mature lymphoid malignancies and occurs early in lymphomagenesis.Narayan G et al
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Citation

Adriana Zamecnikova

+X solely in lymphomas

Atlas Genet Cytogenet Oncol Haematol. 2017-07-01

Online version: http://atlasgeneticsoncology.org/haematological/1800/+x-solely-in-lymphomas