Objective.--To review the role of molecular genetics in the diagnosis of ma
Data Sources and Study Selection.--Primary research studies and reviews pub
lished in the English literature that focus on molecular genetics and malig
nant lymphoma, in particular, clonality, chromosomal translocations, tumor
suppressor genes, and Hodgkin disease.
Data Extraction and Synthesis.--Molecular genetics has an important role in
the assessment of malignant lymphomas. Clonality, detected by Southern blo
t analysis or the polymerase chain reaction, is helpful for establishing th
e diagnosis of lymphoma in lesions with ambiguous morphologic and immunophe
notypic findings. Southern blot analysis is the "gold standard" for clonali
ty assessment, but the process is labor-intensive and time-consuming. Polym
erase chain reaction analysis is more convenient, but a potentially signifi
cant false-negative rate exists in the analysis of some antigen receptor ge
nes as a result of using consensus primers and the process of somatic hyper
mutation. Chromosomal translocations, which result in oncogene activation,
occur in many types of B- and T-cell lymphomas, and their detection is help
ful in classification as well as in establishing a diagnosis of malignancy.
Gene rearrangements and chromosomal translocations also can be used to mon
itor minimal residual disease. Tumor suppressor genes, although their analy
sis is relatively less useful for diagnosis, are involved in both pathogene
sis and tumor progression and will be more important diagnostically as this
field continues to expand. Molecular genetic analysis has played a major r
ole in improving our understanding of Hodgkin disease.
Conclusions.--Molecular genetic tests are currently important ancillary too
ls for the diagnosis and classification of malignant lymphomas, and their r
ole is likely to increase in the future.