KLF2 mutation and its molecular oncogenic mechanism in lymphoma
Based at Division of Molecular Histopathology, Addenbrooke’s Hospital
Supervised by Professor Ming-Qing Du
KLF2, encoding for a transcriptional factor/repressor, is inactivated by mutations in 40% of splenic marginal zone lymphoma (SMZL). KLF2 mutation is significantly associated with expression of stereotypic B-cell receptor, and also mutation in several regulators of the NOTCH and NF-kB pathway. The mutation in KLF2 abolishes its ability to suppress NF-kB activation by both canonical and non-canonical pathways. The proposed PhD project will investigate the genes and transcriptional regulators modulated by KLF2 and decipher the pathogenic role of KLF2 inactivation and its oncogenic cooperation with other genetic changes in SMZL.
Clipson A, Wang M, de Leval L, Ashton-Key M, Wotherspoon A, Vasilliou G, Bolli N, Grove C, Moody S, Escudero-Ibarz L, Gundem G, Brugger K, Xue X, Mi E, Bench A, Scott M, Liu H, Follows G, Robles EF, Martinez Climent JA, Oscier D, Watkins AJ, Du MQ. KLF2 mutation is the most frequent somatic change in splenic marginal zone lymphoma and identifies a subset with distinct genotype. Leukemia 2015; 29(5): 1177-85. doi: 10.1038/leu.2014.330.
Xue X, Zeng N, Gao Z, Du MQ. Diffuse large B-cell lymphoma: sub-classification by massive parallel quantitative RT-PCR. Lab Investigation. 2015; 95(1): 113-20.
Wang M, Escudero-Ibarz L, Moody S, Zeng N, Clipson A, Huang Y, Xue X, Grigoropoulos NF, Barrans S, Worrillow L, Forshew t, Rosenfeld N, Su J, Firth A, Martin H, Jack A, Brugger K, Du MQ. Somatic mutation screening using archival formalin-fixed paraffin-embedded tissues by Fluidigm Access Array multiplex PCR and Illumina MiSeq sequencing. Journal of Molecular Diagnostics 2015 Jul 9. pii: S1525-1578(15)00125-7. doi: 10.1016/j.
Clipson A, Barrans S, Zeng N, Crouch S, Grigoropoulos NF, Liu H, Kocialkowski S, Wang M, Huang Y, Worrillow L, Goodlad J, Buxton J, Neat M, Fields P, Wilkins B, Grant JW, Wright P, EI-Daly H, Follows GA, Watkins AJ, Jack A, Du MQ. The prognosis of MYC translocation positive diffuse large B-cell lymphoma depends on the second hit. Journal of Pathology Clinical Research 30 Mar 2015 DOI: 10.1002/cjp2.10
Nie Z, Du MQ, McAllister-Lucas LM, Lucas PC, Bailey NG, Hogaboam CM, Lim MS, Elenitoba-Johnson KSJ. Conversion of the LIMA1 tumour suppressor into an oncogenic LMO-like protein by API2-MALT1 in MALT lymphoma. Nat Communications . 2015 Jan 8;6:5908. doi: 10.1038/ncomms6908.
More information on the supervisor’s research can be found on their research group website