Mantle cell lymphomas with concomitant MYC and CCND1 breakpoints are recurrently TdT positive and frequently show high-grade pathological and genetic features.

Chromosomal breakpoints involving the MYC gene locus, frequently referred to as MYC rearrangements (MYC - R+), are a diagnostic hallmark of Burkitt lymphoma and recurrent in many other subtypes of B-cell lymphomas including follicular lymphoma, diffuse large B-cell lymphoma and other high-grade B-cell lymphomas and are associated with an aggressive clinical course. In remarkable contrast, in MCL, only few MYC - R+ cases have yet been described. In the current study, we have retrospectively analysed 16 samples (MYC - R+, n = 15, MYC - R-, n = 1) from 13 patients and describe their morphological, immunophenotypic and (molecular) genetic features and clonal evolution patterns.

MYC expression and translocation analyses in low-grade and transformed follicular lymphoma.

Aims: Low-grade follicular lymphoma (FL) (grade 1/2, FL1/2) has an annual risk of transformation of ≈3%, which is associated with aberrations in CDKN2A/B, TP53, and MYC. As in diffuse large B-cell lymphoma, high MYC expression in transformed FL (tFL) might predict a MYC breakpoint.

Methods And Results: We quantified MYC expression by immunohistochemistry and digital analysis in 41 paired biopsies from 20 patients with FL1/2 with subsequent transformation and in four isolated biopsies of tFL.

JNK is constitutively active in mantle cell lymphoma: cell cycle deregulation and polyploidy by JNK inhibitor SP600125.

Mantle cell lymphoma (MCL) is characterized by genetic instability and a poor prognosis. Many blastoid variants are (hypo)tetraploid and have an even worse prognosis. We investigated the role of signalling by mitogen-activated protein kinases (MAPKs) in MCL.

Array comparative genomic hybridization reveals a very high frequency of deletions of the long arm of chromosome 6 in testicular lymphoma.

Despite the fact that numerous studies have been performed on diffuse large B-cell lymphoma (DLBCL), only few have concerned extranodal lymphomas occurring in the testis. We performed a cytogenetic and molecular study of 17 testicular non-Hodgkin lymphomas, of which 14 were proven primary DLBCL of the testis. Cytogenetic analysis revealed in 8 out of 11 evaluable cases a structural abnormality of the long arm of chromosome 6, with deletion or addition of material of unknown origin, and with breakpoints spanning the region 6q12-6q23.

Molecular, cytogenetic, and immunophenotypic characterization of follicular lymphoma grade 3B; a separate entity or part of the spectrum of diffuse large B-cell lymphoma or follicular lymphoma?

We studied a histological homogeneous group of 29 cases with the diagnosis of follicular lymphoma (FL) grade 3B (FL3Bs). In a previous study, we subdivided this group in 3 subgroups based on (1) aberrations of the 3q27 region, (2) lack of 3q27 and t(14;18), and (3) the presence of a t(14;18). In this study, we further characterized the FL3B lymphomas that are currently part of the spectrum of FL in the WHO classification, taking into account other cytogenetical aberrations, immunohistochemistry for P53, bcl2, bcl6, and CD10, rearrangement of the proto-oncogene myc, and mutation of the tumor suppressor gene TP53.

BCL6 alternative translocation breakpoint cluster region associated with follicular lymphoma grade 3B.

Translocations involving band 3q27, affecting the major breakpoint region (MBR) of BCL6, are common in diffuse large B-cell lymphomas (DLBCLs). Recent data suggest an alternative breakpoint cluster region (ABR) located between 245 and 285 kb 5' of BCL6, which might be associated with Follicular Lymphoma (FL). Ten DLBCLs and 9 FLs grade 3B with cytogenetic rearrangements at 3q27 were studied by fluorescence in situ hybridization (FISH) to discriminate between breakpoints at the ABR and MBR.

Splenic marginal zone lymphomas presenting with splenomegaly and typical immunophenotype are characterized by allelic loss in 7q31-32.

Splenic marginal zone lymphoma (SMZL) is a rare non-Hodgkin's lymphoma that recently has been recognized as an entity. The first goal of this study was to identify potential chromosomal aberrations in this entity by cytogenetic analysis and comparative genomic hybridization (CGH). The second goal was to assess the frequency of 7q31-32 allelic imbalances in SMZL with primary involvement of the spleen and the typical immunophenotype (IgM+; IgD(dim); and CD5-, CD10-, and CD23-).

Identification of chromosomal copy number changes associated with transformation of follicular lymphoma to diffuse large B-cell lymphoma.

The histological transformation from a follicular lymphoma (FL) to a diffuse large B-cell lymphoma (DLBL) occurs in 22% to 30% of all cases of FL. The aim of this study was to identify specific chromosomal gains/losses associated with transformation of FL to DLBL, in addition to the well-known mechanisms like p53 mutation and protein expression and c-myc translocation and up-regulation. This is the first study to meet 2 important conditions for such a comparison.

Follicular 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.

Chromosomal translocations involving t(14;18)(q32;q21) and the chromosome 3q27 region are common in B-cell non-Hodgkin lymphoma of germinal center cell origin. Grade 3B follicular lymphoma (FL), consisting almost exclusively of centroblasts, is a distinct subgroup of follicular lymphomas that has more in common clinically with the aggressive diffuse large B-cell lymphomas than with their indolent FL grade 1 and 2 counterparts. We studied the cytogenetic and molecular genetic aberrations by classic cytogenetics, polymerase chain reaction, Southern blot hybridization, and fluorescence in situ hybridization, with special emphasis on t(14;18), affecting bcl-2, and 3q27 rearrangement, affecting bcl-6, in 32 cases of FL grade 3B.

Cytogenetic analysis of cryopreserved bone marrow cells.

We studied the results of culturing and karyotyping of fresh BM and defrosted BM cells from 11 patients with cytogenetic abnormalities with the diagnosis of acute myeloid leukemia (AML). In 8 of 11 patients the cytogenetic results from the fresh and defrosted BM were comparable with respect to the amount and quality of abnormal metaphases. In only one patient one abnormal cell-line (out of two) re-appeared in the frozen BM, probably due to selection, and in three patients we found a distinct decrease of amount and quality.

Cytogenetics of three cases of ANLL M2 and M4. Involvement of chromosomal region 8q22 in all three but 21q22 in only one.

Cytogenetic investigation of the bone marrow of two patients with acute nonlymphocytic leukemia (ANLL), French-American-British Cooperative group (FAB) classification M2, revealed a translocation (8;22)(q22.1;q13.3), without involving chromosome 21, and a variant translocation (8;21)(q22;q22).