Lymphomas are cancers arising from the proliferation of the lymphatic cells. These tumours usually develop in the lymph nodes and may be divided into Hodgkin's disease and non-Hodgkin lymphomas (NHL).

Cytogenetics, or the study of chromosome number and chromosome morphology, is routinely used in the diagnosis and characterisation of lymphomas. These studies may be done on lymph-node biopsy specimens or bone-marrow aspirates. Many cancers manifest numerical and/or structural chromosomal changes that are disease specific. Cytogenetic studies are also useful in monitoring disease development and regression. This article will focus on NHL, since it is commoner and better characterised cytogenetically than is Hodgkin's disease.

The vast majority of NHL have clonal or recurring chromosome abnormalities. Compared with leukaemias, malignant lymphomas are more likely to have abnormal karyotypes, and they are also more complex. In about 70% of B-cell neoplasms, the immunologlobulin heavy chain IGH at 14q32 is involved in various translocations.

In Burkitt's lymphoma, the translocation t(8;14)(q24.1;q32) is present in 75-80% of all cases. t(2;8)(p12;q24.1) and t(8;22)(q24.1;q11) variants make up the remainder. The c-MYC oncogene mapped to 8q24.1 is translocated to the IGH locus at 14q32. The juxtaposition of the oncogene with the immunoglobulin chain is thought to lead to inappropriate expression of the oncogene. Other specific chromosomal rearrangements include t(14;18)(q32;q21) in follicular lymphoma (which is the most common translocation in NHL), t(11;14)(q13;q32) in mantle-cell lymphoma, and t(2;5)(p23;q35) in anaplastic large-cell lymphoma. Lymphomas of T-cell origin are characterised by translocations involving the T-cell-receptor genes located at 14q11, 7q34-35, and 7p15.

Fluorescence in-situ hybridisation (FISH) assays accurately detect abnormalities that present either as an abnormal fusion product of the two genes or a disruption of a gene locus due to a translocation. The FISH assay can be used as an adjunct test to cytogenetics.

Karyotype showing the reciprocal translocation between chromosomes 8 and 14 typical of Burkitt's lymphoma (arrows). Clonal expansion is evident from the gains of chromosomes and other structural rearrangements.

 

Dr Alvin Lim		Ms Lim Tse Hui
Senior Principal Scientific Officer		Principal Scientific Officer
Cytogenetics Laboratory		Cytogenetics Laboratory
Dept of Pathology, SGH		Dept of Pathology, SGH