Cytogenetic analysis of 434 consecutively ascertained specimens of non‐Hodgkin's lymphoma: Correlations between recurrent aberrations, histology, and exposure to cytotoxic treatment

Abstract

Cytogenetic abnormalities in non-Hodgkin's Lymphoma (NHL) provide a model system for the analysis of the role of multiple genomic aberrations in human malignancy. In order to define correlations with histology, tumor evolution, and the effects of genotoxic exposure, cytogenetic analysis was performed on 434 specimens of NHL derived from 423 patients consecutively ascertained over a 5-year period (1984-1989). Six recurring translocations (RT) were observed: t(14;18)(q32;q21), t(8;14)(q24;q32), t(11;14)(q13;q32), t(3;22)(q27;11), t(2;5)(p23;q35), and t(1;6)(q21;q25). No translocation was specific to a single histologic subtype. Other structural chromosome abnormalities were analyzed according to break site; groups of related breaks were considered together for statistical analysis. Recurring other structural and numerical aberrations (ROA) encountered in greater than 10% of specimens included rearrangements with breaks at bands 1p32-36, 1q21-23, 6q21-25, and trisomies of chromosomes 7 and 12. ROA with one of these breaks or numerical abnormalities were the sole abnormalities in at least two cases. Correlations were observed among ROA and between ROA and histologic subtypes. Trisomy 7, breaks at 1q21-23, 1p32-36, 6q21-25, and 7q32 were associated with t(14;18); trisomy 18 was associated with trisomy 3; and structural abnormalities of chromosome 17 were associated with breaks at 1p32-36 and 6q21-25. Trisomy 7 and trisomy 12 were more frequent in t(14;18)-bearing intermediate to high grade tumors compared to low grade tumors. Trisomy 12 and breaks at band 1p22 were associated with large cell diffuse lymphomas. Incidence rates of reciprocal translocations, ROA, and measures of karyotypic complexity, including number of breakpoints and marker chromosomes were compared in pretreatment and posttreatment samples. Karyotypic complexity was greater in the posttreatment samples, reflecting an increased frequency of nonrecurring and low incidence aberrations. These results better define the association of genomic aberrations and tumorigenesis, histologic transformation, and tumor progression.

Clonal chromosomal abnormalities as direct evidence for clonality in nasal T/natural killer cell lymphomas

“…This chromosomal aberration is a common change in retinoblastoma, but rarely occurs in acute lymphoblastic leukaemia and lymphoma (Heim & Mitelman, 1995;Fifth International Workshop on Chromosomes in LeukemiaLymphoma, 1987;Offit et al, 1991). In a previous report (Tien et al, 1993), one of four patients with EBV-associated T-cell malignancies (nasal lymphoma was not included in that study) showed isodicentric chromosome 6, idic(6)(pter !…”

Follicular lymphoma grade 3B is a distinct neoplasm according to cytogenetic and immunohistochemical profiles

“…This finding agrees well with the data from other studies, in which MYC translocations were found in up to 13% of cases. 6,[21][22][23][24][25] It is especially interesting to note that the incidence of MYC + cases was the same in the FL/LCC subtype as in the FL3B and DLBCL/FL3B subtypes, making MYC a likely candidate as a progression factor also in "non-transformed" FL. Out of 12 cases of FL with MYC gene translocation, five cases presented with concurrent translocations of either BCL2 or BCL6, while one case of FL3B showed a triple hit of MYC, BCL2 and BCL6.…”

True

“…Recurrent chromosomal aberrations are specifically associated with different lymphoma types [32][33][34] and can serve as diagnostic or prognostic markers. [35][36][37] Furthermore, they may be useful for elucidating disease development and progression.…”