Chromosomal aberrations in angioimmunoblastic T‐cell lymphoma and peripheral T‐cell lymphoma unspecified: A matrix‐based CGH approach

Abstract

Angioimmunoblastic T-cell lymphoma (AILT) is a histopathologically well-defined entity. However, despite a number of cytogenetic studies, the genetic basis of this lymphoma entity is not clear. Moreover, there is an overlap to some cases of peripheral T-cell lymphoma unspecified (PTCL-u) in respect to morphological and genetic features. We used array-based comparative genomic hybridization (CGH) to study genetic imbalances in 39 AILT and 20 PTCL-u. Array-based CGH revealed complex genetic imbalances in both AILT and PTCL-u. Chromosomal imbalances were more frequent in PTCL-u than in AILT and gains exceeded the losses. The most recurrent changes in AILT were gains of 22q, 19, and 11p11-q14 (11q13) and losses of 13q. The most frequent changes in PTCL-u were gains of 17 (17q11-q25), 8 (involving the MYC locus at 8q24), and 22q and losses of 13q and 9 (9p21-q33). Interestingly, gains of 4q (4q28-q31 and 4q34-qtel), 8q24, and 17 were significantly more frequent in PTCL-u than in AILT. The regions 6q (6q16-q22) and 11p11 were predominantly lost in PTCL-u. Moreover, we could identify a recurrent gain of 11q13 in both AILT and PTCL-u, which has previously not been described in AILT. Trisomies 3 and 5, which have been described as typical aberrations in AILT, were identified only in a small number of cases. In conclusion, CGH revealed common genetic events in peripheral T-cell lymphomas as well as peculiar differences between AILT and PTCL-u.

High-resolution analysis of chromosome copy number alterations in angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma, unspecified, with single nucleotide polymorphism-typing microarrays

“…We detected CNAs or LOH regions at a similar frequency in AILT and PTCL-u, consistent with previous data showing a common chromosome gain at 11q13 in the two disorders 10 or common CNAs in PTCL-u and ALK-negative anaplastic largecell lymphoma. 9 Few previous studies have described LOH in AILT or PTCL-u, possibly in part because of a high frequency of uniparental disomy in these conditions, as revealed in our data set (especially in the regions of recurrent LOH), that may be undetectable by conventional array-based CGH.…”

“…In contrast to previous genomic analyses of T-cell lymphoma with CGH, [8][9][10]26 our study based on SNP-typing arrays was able to identify many small regions (o100 kb) with CNAs or LOH in the genome of lymphoma cells.…”

“…CARMA1 interacts with BCL10 and MALT1 and thereby mediates activation of nuclear factor (NF)-kB induced by stimulation of the T-or B-cell receptor. 10 Given that NF-kB frequently is activated and contributes to carcinogenesis in many tumor types, 30 activation of this transcription factor as a result of CARMA1 overexpression may also be important in disease progression and poor outcome of AILT or PTCL-u.…”

“…Array-based CGH with a resolution of 4100 kb has also been used to examine AILT/PTCL-u, revealing recurrent CN gains of 11p11-q14, 19 and 22q in AILT, and of 8, 17 and 22q in PTCL-u. 10 Some inconsistency among these data may reflect the genetic heterogeneity in AILT/PTCL-u, and a low-resolution power in conventional or array-based CGH failed to pinpoint the genes essential to these CNAs.…”

Aspects moléculaires des lymphomes T périphériques (1)

“…Enfin, les déséquilibres observés en CGH (comparative genomic hybridization) diffèrent de ceux retrouvés dans les LAIT ou les LAGC. Il s'agit de gains récurrents des 1q, 3p, 5p, 7q, 8q, 17q et 22q et de pertes des 6q, 10p et 13q [19,51,52].…”