i(3)(q10) in non-Hodgkins lymphoma (NHL)

2018-07-01   Adriana Zamecnikova 

1.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-Hodgkins 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.

Clinics and Pathology

Disease

B-cell non-Hodgkins lymphoma and less frequently T-cell lymphomas.

Note


Phenotype stem cell 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

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.

Bibliography

Pubmed IDLast YearTitleAuthors
121531652002Cytogenetic analysis in mantle cell lymphoma: a review of 214 cases.Au WY et al
68506081983Nonrandom chromosome abnormalities in lymphoma.Bloomfield CD et al
125292932003Follicular lymphoma grade 3B includes 3 cytogenetically defined subgroups with primary t(14;18), 3q27, or other translocations: t(14;18) and 3q27 are mutually exclusive.Bosga-Bouwer AG et al
184492072008The most frequent t(14;19)(q32;q13)-positive B-cell malignancy corresponds to an aggressive subgroup of atypical chronic lymphocytic leukemia.Chapiro E et al
175560732007Detailed characterization of 7q deletions by multicolor banding (mBAND) in marginal zone cell lymphoma.Gazzo S et al
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
107008712000Chromosome abnormalities in peripheral T-cell lymphoma.Lepretre S et al
117193922001Loss of a novel tumor suppressor gene locus at chromosome 8p is associated with leukemic mantle cell lymphoma.Martinez-Climent JA et al
204605022010Deregulation of the telomerase reverse transcriptase (TERT) gene by chromosomal translocations in B-cell malignancies.Nagel I et al
239297562013PCDH10 promoter hypermethylation is frequent in most histologic subtypes of mature lymphoid malignancies and occurs early in lymphomagenesis.Narayan G et al
183416372008Cytogenetic abnormalities and clinical correlations in peripheral T-cell lymphoma.Nelson M et al
159429422005PAX5/IGH rearrangement is a recurrent finding in a subset of aggressive B-NHL with complex chromosomal rearrangements.Poppe B et al
65877771984Chromosome analysis in hematologic disorders. The leukemias.Sandberg AA et al
119433452002Concomitant tetrasomy 3q and trisomy 18 in CD5(-), CD13(+) chronic lymphocytic leukemia.Specchia G et al
166902282007[A cytological, immunophenotypical and cytogenetical study of 136 consecutive cases of B-cell chronic lymphoid hemopathies].Struski S et al
153901882004Application of combined immunofluorescence and fluorescence in situ hybridization on paraffin-embedded sections to characterize T-cell lymphoma with EBV-infected B-cell blasts.Temple GK et al
211277532008Polyclonal B-cell lymphocytosis with binucleated lymphocytes (PPBL).Troussard X et al
93988631997Interphase detection of BCL6/IgH fusion gene in non-Hodgkin lymphoma by fluorescence in situ hybridization.Ueda Y et al
77739661995Concomitant partial tetrasomy 3q and trisomy 18 in Waldenström macroglobulinemia.Wong KF et al
121654582002Gain of chromosome 3/3q in B-cell chronic lymphoproliferative disorder is associated with plasmacytoid differentiation with or without IgM overproduction.Wong KF et al
35378021987Multiple recurrent genomic defects in follicular lymphoma. A possible model for cancer.Yunis JJ et al

Citation

Adriana Zamecnikova

i(3)(q10) in non-Hodgkins lymphoma (NHL)

Atlas Genet Cytogenet Oncol Haematol. 2018-07-01

Online version: http://atlasgeneticsoncology.org/haematological/2115/i(3)(q10)-in-non-hodgkins-lymphoma-(nhl)

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