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i(3)(q10) in non-Hodgkin's lymphoma (NHL)

Written2018-07Adriana Zamecnikova
Kuwait Cancer Control Center, Kuwait annaadria@yahoo.com

Abstract Partial or complete chromosome 3 gains resulting from the presence of trisomy 3, unbalanced translocation or isochromosome formation has been observed in different types of non-Hodgkin's lymphomas (NHL). Among them, the isochromosome of the long arm of chromosome 3 is a relatively rare chromosome aberration, associated mainly with B-cell NHL. However, its occurrence is not restricted to lymphomas, as the detection of +i(3)(q10) is considered a specific marker of polyclonal B-cell lymphocytosis with binucleated lymphocytes (PPBL) associated with an increase frequency of chromosome 3 instability as well as it may also be found in myeloid malignancies.

Keywords chromosome 3; B-cell lymphomas; T-cell lymphomas

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Identity

ICD-Topo C420,C421,C424
ICD-Morpho 9690/3 Follicular lymphoma; Paediatric follicular 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 9673/3 Mantle cell lymphoma
ICD-Morpho 9823/3 Chronic lymphocytic leukaemia /small lymphocytic lymphoma
ICD-Morpho 9689/3
ICD-Morpho 9699/3 Extranodal marginal zone lymphoma of mucosa- associated lymphoid tissue (MALT lymphoma); Nodal marginal zone lymphoma; Paediatric nodal marginal zone lymphoma
ICD-Morpho 9761/3 Waldenstrom macroglobulinemia
ICD-Morpho 9705/3 Angioimmunoblastic T-cell lymphoma
ICD-Morpho 9702/3 Peripheral T-cell lymphoma, NOS; Anaplastic large cell lymphoma, ALK negative
Atlas_Id 2115

Clinics and Pathology

Disease B-cell non-Hodgkin's lymphoma and less frequently T-cell lymphomas.
Note
Phenotype / cell stem origin Patients had various forms of lymphomas:
Mature B-cell lymphomas in 20: 4 follicular lymphoma (FL) (Yunis et al .,1987; Ueda et al., 1997; Horsman et al., 2001; Bosga-Bouwer et al., 2003), 4 diffuse large B-cell lymphoma (DLBCL) (Poppe et al., 2005; Yoshioka et al., 2005; Chapiro et al., 2008; Arayan et al., 2013), 3 mantle cell lymphoma ID: 2062> (MCL) (Martinez-Climent et al., 2001; Au et al., 2002; Nagel et al .,2010), 3 chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) (Specchia et al., 2002; Wong et al., 2002; Struski et al., 2007), 1 splenic marginal zone B-cell lymphoma (Gazzo et al., 2007), 1 nodal marginal zone B-cell lymphoma (Chapiro et al., 2008), 1 Waldenström macroglobulinemia (Wong et al., 1995) and 3 mature B-cell neoplasms (Sandberg et al., 1984; Bloomfield et al., 1983; Hashimoto et al., 1995).
Mature T-cell lymphomas in 3: 2 angioimmunoblastic T-cell lymphoma (Lepretre et al., 2000; Temple et al., 2004) and 1 peripheral T-cell lymphoma, unspecified (Nelson et al., 2008).
Epidemiology 23 patients (male prevalence; 15 males, 8 females aged 52 to 83 years; median 64 years).
Prognosis Gain of 3q in complex karyotypes reflects genomic instability and patients may show a more aggressive course of the disease and poor response to chemotherapy.

Cytogenetics

Note FISH using a probe specific for 3q such as the probe for BCL6 is recommended for the confirmation of 3q trisomy in complex karyotypes. Moreover, as the method is more sensitive than conventional cytogenetics, it allows for the study of non-dividing cells in lymphomas.
Cytogenetics Morphological Presents as 1 normal chromosome 3 and a i(3)(q10) chromosome replacing a normal chromosome 3, leading to trisomy 3q and monosomy 3p in 13 patients and presents as 2 normal chromosomes 3 and an extra +i(3)(q10) resulting in disomy 3p and 3q tetrasomy in 10.
Additional anomalies Found as a part of simple karyotypes associated with +18 in 2 CLL and in a Waldenstrom macroglobulinemia patient and part of complex or highly complex rearrangements in the remaining patients. Characteristic chromosomal abnormalities associated with particular subtypes such as 14q rearrangements were found in 9 patients with B-cell NHL, among them the t(14;19)(q32;q13) was detected in 2, t(3;14)(q27;q32) in 2, t(14;18)(q32;q21) in 1, t(9;14)(p13;q32) in 1 and t(11;14)(q13;q32) in 3 patients with mantle cell lymphoma.

Result of the chromosomal anomaly

Fusion Protein
Oncogenesis Isochromosome i(3)(q10) represents a rare but recurrent abnormality in NHL, particularly in B-cell lineage lymphomas. The formation of i(3)(q10) results in a duplication of its long arm, leading to genomic imbalances in a copy number-dependent manner. Commonly overrepresented segments in complete or partial trisomies of 3q include the q21-23 region and the q25-29 region, however the gene(s) involved in pathogenesis are not known. Candidate genes on 3q may include BCL6 located on 3q27.3, MECOM on 3q26.2, SIAH2 on 3q25.1, PIK3CA on 3q26.32, PAK2 on 3q29 and the ATR gene located on 3q23. Deregulation of these genes could contribute to a possible proliferative advantage of the cells. i(3)(q10) is frequently part of a complex karyotype, therefore may be considered a secondary event. The appearance of i(3)(q10) might be related to chromosomal and genomic instability (Troussard et al., 2008) that may play a role in the emergence of a clonal and/or malignant subpopulation in NHL as a part of a multi-step process.
  

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Citation

This paper should be referenced as such :
Zamecnikova A
i(3)(q10) in non-Hodgkin's lymphoma (NHL);
Atlas Genet Cytogenet Oncol Haematol. in press
On line version : http://AtlasGeneticsOncology.org/Anomalies/i3q10ID2115.html


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