Molecular Pathology of Lymphoma: Applications in Diagnosis and Prognosis
University of Cambridge
Tennis Court Road
Lymphomas are a group of highly heterogeneous tumors derived from B or T lymphocytes and occur at both nodal and extranodal sites. The accurate diagnosis of various lymphoma subtypes is critical in clinical management and this depends on integrated histological, immunophenotypic and molecular investigations. We have been undertaking a series of research programmes to elucidate the pathology, immunophenotype, and molecular genetics of several lymphoproliferative disorders, particularly mucosa-associated lymphoid tissue (MALT) lymphoma, splenic marginal zone lymphoma (SMZL), diffuse large B-cell lymphoma (DLBCL), enteropathy associated T cell lymphoma (EATL), Kaposi sarcoma herpes virus (KSHV) associated lymphoproliferative disorders.
By array comparative genomic hybridisation (CGH), we have identified a number of genetic targets in these lymphomas. For example, we have identified A20, a “global” NF-kB inhibitor, as the target of 6q23 deletion in ocular adnexal MALT lymphomas, which do not carry the chromosome translocations seen in this lymphoma entity. Subsequent investigations show that A20 is also inactivated by somatic mutation and promoter methylation, and complete A20 inactivation is associated with poor clinical outcome in ocular adnexal MALT lymphoma. We are currently extending these observations to investigate comprehensively the genetics of translocation negative MALT lymphoma. We are also undertaking a series of research investigations aiming to characterise the genetics of SMZL and EATL, and validate potential biomarkers of potentially valuable in prognosis and treatment stratification of DLBCL.
- Research Associates:
Alex Clipson, Wenhan Deng, Helen Heath, Ming Wang, A James Watkins.
- Clinical Scientist:
- Clinical Research Fellow:
- Graduate Students:
Leire Escudero Ibarz
- Visitor Graduate Student:
- Visitor Researcher:
- Bi Y, Zeng N, Chanudet E, Huang Y, Hamoudi RA, Liu H, Dong G, Watkins AJ, Ley SC, Zou L, Chen R, Zhu X, Du MQ. A20 inactivation in ocular adnexal MALT lymphoma. Haematologica 2012; 97(6):926-30.
- Rosebeck S, Madden L, Jin X, Gu S, Apel IJ, Appert A, Hamoudi RA, Noels H, Sagaert X, Van Loo P, Baens M, Du MQ, Lucas PC, McAllister-Lucas LM. Cleavage of NIK by the API2-MALT1 fusion oncoprotein leads to noncanonical NF-kappaB activation. Science 2011, 331:468-472.
- Hamoudi RA, Appert A, Ye H, Ruskone-Fourmestraux A, Streubel B, Chott A, Raderer M, Gong L, Wlodarska I, De Wolf-Peeters C, MacLennan KA, de Leval L, Isaacson PG, Du MQ. Differential Expression of NF-B target genes in MALT lymphoma with and without chromosome translocation: insights into molecular mechanism. Leukaemia 2010 Aug;24(8):1487-97.
- Liu H, Brais R, Lavergne-Slove A, Zeng Q, Payne K, Ye H, Liu Z, Carreras J, Huang Y, Bacon CM, Save V, Venkatraman L, Isaacson PG, Woodward J, Du MQ. Continual Monitoring of Intraepithelial Lymphocyte Immunophenotype and Clonality Is More Important Than Snapshot Analysis in the Surveillance of Refractory Coeliac Disease. Gut 2010; 59(4):452-60.
- Isaacson PG, Du MQ. MALT lymphoma: from morphology to molecule. Nature Review Cancer 2004; 4:644-53.