+X solely in lymphomas

Abstract

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

Keywords

X chromosome gain, malignant lymphoma, chronic lymhocytic leukemia, gene downregulation.

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Identity

ICD-Topo	C420,C421,C424
ICD-Morpho	9823/3 Chronic lymphocytic leukaemia /small lymphocytic lymphoma
ICD-Morpho	9700/3 Mycosis fungoides
ICD-Morpho	9701/3 Sezary syndrome
ICD-Morpho	9827/3 Adult T-cell leukaemia/lymphoma
ICD-Morpho	9705/3 Angioimmunoblastic T-cell lymphoma
ICD-Morpho	9680/3 Diffuse large B-cell lymphoma (DLBCL), NOS; Primary DLBCL of the CNS; Primary cutaneous DLBCL, leg type; EBV positive DLBCL of the elderly; DLBCL associated with chronic inflammation; B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and Burkitt lymphoma
ICD-Morpho	9650/3 Classical Hodgkin lymphoma
ICD-Morpho	9663/3 Nodular sclerosis classical Hodgkin lymphoma
ICD-Morpho	9702/3 Peripheral T-cell lymphoma, NOS; Anaplastic large cell lymphoma, ALK negative
ICD-Morpho	9689/3
ICD-Morpho	9673/3 Mantle cell lymphoma
ICD-Morpho	9690/3 Follicular lymphoma; Paediatric follicular lymphoma
Atlas_Id	1800

Clinics and Pathology

Disease	B- and T-cell lymphomas and chronic lymhocytic leukemia (CLL).
Phenotype / cell stem 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/Age B>Disease B>Karyotype 1 F/75$ Mycosis fungoides/Sezary syndrome 46,XX,dmin/47,XX,+X 2 F/62 Adult T-cell lymphoma/leukemia (HTLV-1+) 46,XX,add(2)(p13),del(3)(q2?1q2?5)/45,X,-X/47,XX,+X 3 M/75 Angioimmunoblastic T-cell lymphoma 47,XY,+X/47,idem,del(10)(p12)          LN 4 F/64 Angioimmunoblastic T-cell lymphoma  47,XX,+X          LN 5 F/73 Diffuse large B-cell lymphoma 47,XX,+X          LN 6 M/82 Mature B-cell neoplasm, NOS 47,XY,+X          LN 7 F/63 Angioimmunoblastic T-cell lymphoma 47,XX,+add(3)(p11)/47,XX,+X          LN 8 M/49 Hodgkin disease, NOS 47,XY,+X          LN 9 M/72 Diffuse large B-cell lymphoma 47,XY,+X          LN 10 F/63 Angioimmunoblastic T-cell lymphoma 49,XX,+5,+19,+21/47,XX,+X/46,XX,inv(14)(q11q32)/45,X,-X          LN 11 F/78 Angioimmunoblastic T-cell lymphoma 47,XX,+X          LN 12 F/47 Angioimmunoblastic T-cell lymphoma 47,XX,+X          LN 13 F/35 Hodgkin disease, nodular sclerosis 78-82,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/65 Peripheral T-cell lymphoma, unspecified 47,XX,+X 15 M/54 Mature 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/78 Mature T- and NK-cell neoplasm, NOS 47,XY,+X          LN 17 F/64 Mycosis 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/89 Mature B-cell neoplasm, NOS 47,XX,+12/47,XX,+X          LN 19 F/57 Splenic marginal zone B-cell lymphoma 47,XX,+X          LN 20 F/60 Mantle cell lymphoma 80-88,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 F Diffuse large B-cell lymphoma 47,XX,+X          LN 22  F/16 Hodgkin disease, nodular sclerosis 47,XX,+X          LN 23 F Follicular lymphoma 47,XX,+X           LN 24 F/73 Splenic marginal zone B-cell lymphoma 46,XX,dup(1)(?q12?q31),del(7)(q32q36)/47,XX,+X          LN 25 F/32 Adult T-cell lymphoma/leukemia (HTLV-1+) 47,XX,+X/49,XX,+del(3)(p13),+5,+11 26 M/51 Follicular lymphoma 47,XY,+X/49,idem,t(14;18)(q32;q21),+i(18)(q10),+21          LN 27 F/62 Follicular lymphoma 51,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 M Follicular lymphoma 47,XY,+X/47-49,idem,+7,t(9;10)(p10;q10),t(14;18)(q32;q21),+21 LN 29 M/51 Follicular lymphoma 47,XX,+X/49-52,XY,+X,+2,+12,t(14;18)(q32;q21),+21,+mar          LN 30 F Nodal marginal zone B-cell lymphoma 48,XX,+3,del(11)(q23),del(13)(q12q14),+18/47,XX,+X          LN 31 M Mature 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/75 Nodal marginal zone B-cell lymphoma 47,XX,+X          LN 33 M/36 Diffuse large B-cell lymphoma 47,XY,+X 34 F/40 Post-transplant lymphoproliferative disorder 47,XX,+X          primary non-Hodgkin lymphoma 35 M Follicular 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/85 Nodal marginal zone B-cell lymphoma 46,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/54 Diffuse large B-cell lymphoma 55,XY,+X,+2,+3,t(8;14)(q24;q32),t(14;18)(q32;q21)/47,XY,+X          LN 38 F/44 Diffuse large B-cell lymphoma 47,XX,+X,t(8;14)(q24;q32),t(14;18)(q32;q21)/47,XX,+X           LN 39 M/50 Splenic marginal zone B-cell lymphoma 47,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/Age Karyotype 1 F/40 47,XX,+X 2 F/59 47,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 F 47,XX,+X 4 F/79 47,XX,+X/46,XX,-1,+15 5 F 47,XX,+12/47,idem,del(13)(q12q14)/47,XX,+X 6 F 47,XX,+X 7 F 47,XX,+X 8 F 45,X,-X/47,XX,+X 9 F 46,XX,del(6)(q15q22)/47,XX,+X 10 F 47,XX,+X 11 M 47,XY,+X 12 F 47,XX,+X,inv(9)(p13q12)c 13 M 47,XY,+X 14 M 45,XY,der(8;17)(q10;q10)/46-47,XY,+X 15 F 47,XX,+X 16 F 47,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

Cytogenetics Morphological	Out of 39 lymphoma patients, the extra chromosome X was found in a sideline in 22 cases: Found in association with t(8;14)(q24;q32) and t(14;18)(q32;q21) in 1 DLCL (Niitsu et al., 2009), t(14;18)(q32;q21) in 5 FL (Horsman et al., 2001; Goodlad et al., 2003; Fan and Rizkalla., 2003; Rajgopal et al., 2003; Aamot et al., 2007), t(11;14)(q13;q32) in 1 MCL (Siebert et al., 1998), del(11)(q23) and del(13)(q12q14) in 1 NMZL (Cook et al., 2004), t(14;19)(q32;q13) in 1 NMZL (Martin-Subero et al.,2007), t(11;14)(q13;q32) in 1 MCL (Siebert et al., 1998) and miscellaneous anomalies in 4 B-cell lymphomas (Schlegelberger et al., 1994; Coignet et al., 1996; Le Baccon et al., 2001; Cook et al., 2004). Associated withinv(14)(q11q32) in 1 patient with angioimmunoblastic T-cell lymphoma (Schlegelberger et al., 1990) and miscellaneous anomalies in 7 patients with T-cell lymphomas (van Vloten et al., 1979; Sanada et al 1986; Godde-Salz et al., 1987; Kaneko et al., 1988; Hashimoto et al., 1995; Limon et al 1995; Itoyama et al 2001). Found in a sideline in 7 out of 16 CLL patients. Among them: in association with +12 in 3 (Ohtaki et al., 1986; Mould et al., 1996; Lopez et al., 2012), -X in 1 (Geisler et al., 1997), del(6)(q15q22) in 1 (Geisler et al .,1997), der(8;17)(q10;q10) in 1 (Geisler et al., 1997); and -1, +15 in 1 (Arif et al., 1995).
	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.

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Citation

This paper should be referenced as such :

Zamecnikova A

+X solely in lymphomas;

Atlas Genet Cytogenet Oncol Haematol. in press

On line version : http://AtlasGeneticsOncology.org/Anomalies/plusXID1800.html

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indexed on : Mon May 14 13:38:50 CEST 2018

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