Molecular signatures in the diagnosis and management of follicular lymphoma.
OBJECTIVE
Although karyotypic events in follicular lymphoma and its transformation to aggressive lymphoma have been well described, the underlying genetic changes have until recently remained obscure. Both germline and acquired molecular events are now known to predict disease risk and outcome, respectively. Recent developments in these fields are covered within this review.


RESULTS
Identification of a region of germline predisposition on chromosome 6p together with pesticide influence on disease-related changes suggests specific risk factors for follicular lymphoma. The profiling of S(mu) and immunoglobulin heavy-chain locus (IgH-VH) mutations in follicular lymphoma and relapse/transformed samples suggests divergent evolution from a common progenitor, whereas modular expression profiling highlights the stem cell-like origin of disease. Furthermore, methylation profiling indicates a significant epigenetic influence on disease and novel gene mutations provide exciting new targets for investigation.


CONCLUSIONS
Recent insights into follicular lymphoma identify constitutional and environmental predisposition further unravelling the concept of a lymphoma-initiating cell and the acquired events defining this disease. The major challenge remains successful translation of these findings into routine clinical practice.
Wrench
David
D
Centre for Medical Oncology, Barts and the London School of Medicine, Queen Mary University of London, Charterhouse Square, London, UK. d.j.wrench@qmul.ac.uk
Montoto
Silvia
S
Fitzgibbon
Jude
J
D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D019175:DNA Methylation; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008224:Lymphoma, Follicular / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D009154:Mutation; D014178:Translocation, Genetic