Prognostic value of chromosomal abnormalities in follicular lymphoma

Abstract

The t(14;18)(q32;q21) chromosomal translocation is observed in more than 75% of cases of follicular lymphoma. Several additional chromosomal abnormalities, which might contribute to tumor progression, have also been described. However, prognostic implications of cytogenetic features in follicular lymphoma have not been clearly established. In an attempt to correlate cytogenetic findings with clinical outcome, we have studied survival and risk of transformation into a more aggressive lymphoma in 66 follicular lymphoma patients from whom a lymph node had been karyotyped at the time of diagnosis. A t(14;18) was the most common abnormality, having been observed in 51 patients (77%), but this showed no correlation with clinical outcome. Seventeen other recurrent numerical or structural abnormalities were identified in more than 10% of the patients. A high percentage of cells (> or = 90%) with abnormal metaphases and a number of chromosomal breaks higher than 6 were associated with a poor survival (P > .01 each). Patients with an abnormality of chromosome region 1p21–22 (P < .01), of 6q23–26 (P < .001), or of the short arm of chromosome 17 (P < .001) had a significantly shorter survival in univariate analysis. Multivariate analysis identified a break at 6q23–26 (P = .01) and 17p (P = .01) as independent prognostic factors in this population. The risk of transformation into a diffuse large-cell lymphoma was significantly higher in patients with either a 6q23–26 (P < .001) or a 17p (P < .01) abnormality. Chromosomal analysis of follicular lymphoma at the time of diagnosis can thus provide important information about the risk of transformation and survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Multicolour fluorescence in situ hybridization analysis of t(14;18)‐positive follicular lymphoma and correlation with gene expression data and clinical outcome

“…How the pertinent secondary chromosomal changes correlate with, and affect the expression levels of, genes localized to the affected chromosomes needs to be explored further. It has been determined previously that deletions of 1p, 6q and 17p may negatively influence survival (Tilly et al , 1994; Tilly, 1996; Viardot et al , 2001, 2002). However, the data presented here clearly show that chromosomal gains correlate very closely with overexpressed genes, suggesting that altered copy number with the resultant gene dosage alterations is an important mechanism underlying clonal evolution and disease progression in FL.…”

“…Variable patient outcomes are seen among patients with t(14;18) FL, and improved prognostic indicators are needed to guide clinical management strategies (Mandigers et al , 2001). Cytogenetic analysis has proved to be a valuable tool for the identification of distinct genetic alterations in different histopathological entities and has provided important insights into the pathogenesis of FL (Yunis et al , 1987; Tilly et al , 1994; Bentz et al , 1996; Tilly, 1996; Rao et al , 1998; Weisenburger et al , 2000). Further characterization of the secondary cytogenetic abnormalities, in combination with clinical information such as the IPI, may enable the more precise stratification of patients into prognostic categories.…”

“…Secondary alterations are evident in the great majority of FL cases at diagnosis and become more numerous and complex during disease progression. Transformation to more aggressive disease may thus be directly influenced by secondary chromosomal changes (Yunis et al , 1987; Tilly et al , 1994; Johansson et al , 1995).…”

“…A number of recent studies and reviews have documented in detail the frequency and pattern of secondary chromosomal alterations present at diagnosis in FL (Tilly et al , 1994; Knutsen, 1998; Horsman et al , 2001). The average number of secondary chromosomal alterations at diagnosis is nine, when considering all aneuploidies and the breakpoint sites associated with balanced and unbalanced translocations, deletions and duplications.…”

“…The most common of these secondary alterations are an extra copy of the der(18)t(14;18) and involvement of chromosome 1 in the form of balanced or unbalanced translocations, insertions, deletions and duplications involving the p and q arms (Horsman et al , 2001; Lestou et al , 2002, 2003). Marker chromosomes and other unresolved chromosomal additions are detected in 50% of FL karyotypes (Tilly et al , 1994; Knutsen, 1998; Horsman et al , 2001). Despite the well‐described features of clonal evolution in FL, the chromosomal content of the frequent marker and ring chromosomes, additions and possible cryptic rearrangements remain unresolved by standard cytogenetic testing and therefore are not considered in karyotype–clinical correlation studies.…”