Analysis of secondary chromosomal alterations in 165 cases of follicular lymphoma with t(14;18)

Abstract

Follicular lymphoma is characterized by the t(14;18) in up to 85% of cases. Almost all cases display evidence of secondary chromosomal alterations at initial diagnosis. The influence of recurrent secondary changes on disease progression has not been fully determined. The purpose of this study was to define the full spectrum of recurrent karyotypic events present at diagnosis in a large cohort of cases and to evaluate the sequence of cytogenetic evolution in relation to morphologic progression. A total of 165 cases of follicular lymphoma with t(14;18) were ascertained for which complete clinical information, histopathology, immunophenotype, and karyotype were available. One hundred sixty cases showed secondary alterations with an average of 7.9 additional changes per case. Recurrent alterations seen at the 10% or greater level included +X, +1q21-q44, +7, +12q, +18q, del(1)(p36), del(6q), del(10)(q22-q24), the development of polyploidy and sidelines, and the presence of extra marker chromosomes and chromosomal additions. Changes that correlated with morphologic progression included del(1)(p36), del(6q), del(10)(q22-q24), +7, the total number of abnormalities, the number of markers and additions, and the presence of polyploidy. The most frequent second event arising after the t(14;18) was duplication of the der(18)t(14;18). This study demonstrates that the number and type of secondary chromosomal alterations in follicular lymphoma is highly variable between cases, but that a relatively small number of changes are seen repeatedly in different combinations. A consistent pattern of cytogenetic evolution could not be identified. Potentially significant gene duplications or amplifications may be disguised within marker chromosomes and additions. Additional cytogenetic investigation is required to decipher the karyotypic complexity associated with the progression of follicular lymphoma.

Microarray‐based genomic profiling reveals novel genomic aberrations in follicular lymphoma which associate with patient survival and gene expression status

“…Accordingly, a higher frequency of genomic aberrations per case (2.7-fold) was detected in comparison to previous analysis (Viardot et al, 2002;Hö glund et al, 2004). Our results were highly concordant regarding the localization of chromosomal imbalances larger than 10 Mb when compared with data of previous molecular cytogenetic investigations (Tilly et al, 1994;Avet-Loiseau et al, 1997;Horsman et al, 2001;Ott et al, 2002;Viardot et al, 2002). The increase in the detection of imbalances using array-CGH is caused by the enhancement of resolution resulting in both, the identification of a higher frequency of minimal alterations in critical regions as well as the detection of new recurrent aberrations (Solinas-Toldo et al, 1997;Pinkel et al, 1998;Lichter et al, 2000).…”

“…Given the morphological, cytogenetic, and clinical heterogeneity of FL, we aimed at identifying previously unknown chromosomal imbalances and the more detailed characterization of those regions that have been described in the past (Tilly et al, 1994;Bentz et al, 1996;Avet-Loiseau et al, 1997;Horsman et al, 2001;Neat et al, 2001;Viardot et al, 2001Viardot et al, , 2002Ott et al, 2002;Hö glund et al, 2004). The percentage of chromosomal aberrant tumor specimens was notably higher with array-CGH than with conventional CGH (89% versus 79% in Avet-Loiseau et al, 1997;70% in Viardot et al, 2002).…”

“…However, the sole presence of this translocation is not sufficient for emergence of FL (McDonnell and Korsmeyer 1991). In this context, a large number of genomic gains and losses were described using chromosome banding analysis, conventional comparative genomic hybridization (CGH), or single nucleotide polymorphism chip technologies (Tilly et al, 1994;Bentz et al, 1996;Avet-Loiseau et al, 1997;Horsman et al, 2001;Neat et al, 2001;Viardot et al, 2001Viardot et al, , 2002Ott et al, 2002;Hö glund et al, 2004;Berglund et al, 2007;Ross et al, 2007). Because of the restricted spatial resolution of most of these techniques, it can be speculated that a large number of aberrations have not been identified so far.…”

BCL2 mutations in diffuse large B-cell lymphoma

“…23 For samples in which non-synonymous BCL2 mutations were detected, FFPET were retrieved for FISH analysis. Samples containing 45% of cells displaying break-apart signals were considered positive for the presence of a translocation.…”

Diffuse blastoid B-cell lymphoma: a histologically aggressive variant of t(14;18)-negative follicular lymphoma

“…[31][32][33][34] Gain of chromosome 7 is also frequently detected in diffuse large B-cell lymphoma, especially in those that transformed from low-grade follicular lymphomas. 35 Instead of a gain, we detected a loss of chromosome 7 in four of five cases of diffuse blastoid B-cell lymphoma.…”