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U.S. National Institutes of Health
Cancer Diagnosis Program Cancer Imaging Program Cancer Therapy Evaluation Program Developmental Therapeutics Program Radiation Research Program Translational Research Program Biometric Research Branch Office of Cancer Complementary and Alternative Medicine
Last Updated: 04/25/2012

SCIENTIFIC ADVANCES

Contributed by Dr. George Wright

Dr. George Wright has continued his collaboration with the CCR laboratory of Dr. Lou Staudt and associated international collaborators. Dr. Wright’s recent work has centered on the analysis of data produced by the Solexa sequencer. The data produced by this sequencer were used to identify protein binding sites, copy number change, histone modification, and RNA interference, each of which presented different analysis challenges.

Additionally he collaborated with scientists at the University of Nebraska in the analysis of copy number variation in follicular lymphoma and with scientists in Wurzberg, Germany in a similar analysis for mantle cell lymphoma. Other projects include the evalution of an RNA protection assay to allow for diagnosis of lymphoma subtypes using paraffin preserved tissue and an ongoing collaboration with the University of Maryland to explore the creation of gene networks. Dr. Wright has collaborated with NCI clinical investigator Dr. Wyndham Wilson,in designing phase two trials for a BTK (Bruton’s Tyrosine Kinase) inhibitor and for another inhibitor in treating relapsed and refractory Diffuse Large B-Cell Lymphoma (DLBCL). Additionally he began work with Dr. Wilson and Dr. Elaine Jaffe on a project to molecularly characterize gray-zone lymphoma, a rare lymphoma subtype which shares pathological characteristics of mediastinal DLBCL and Hodgkin lymphoma, but which appears to have worse prognosis than either of those subtypes.

As the primary statistician for the Lymphoma Leukemia Molecular Profiling Project (LLMPP), Dr. Wright collaborated with Dr. Lisa Rimza of the Southwest Oncology Group in writing a successful grant application. Project investigators will evaluate alternative array platforms that would work with paraffin embedded tissue so as to develop a clinical tool that would assist in lymphoma subtyping and prognosis evaluation. As part of this project, Dr. Wright has generated lists of genes to be included on a custom assay to optimally perform all desired predictions. In the past year, Dr. Wright and the other NIH members of the LLMPP were awarded an NCI merit award and a NIH director’s award for “outstanding advancement in the molecular diagnosis and prognosis of cancers through their pioneering work in molecular profiling.”

Other collaborations include acollaboration with LLMPP members at the University of Nebraska to investigate T-cell subtypes and a collaboration between NCI and the University of Maryland physics department to investigate gene network modeling and pathway dependence.

Davis RE, Ngo VN, Lenz G, Tolar P, Young RM, Romesser PB, Kohlhammer H, Lamy L, Zhao H, Yang Y, Xu W, Shaffer AL, Wright G, Xiao W, Powell J, Jiang JK, Thomas CJ, Rosenwald A, Ott G, Muller-Hermelink HK, Gascoyne RD, Connors JM, Johnson NA, Rimsza LM, Campo E, Jaffe ES, Wilson WH, Delabie J, Smeland EB, Fisher RI, Braziel RM, Tubbs RR, Cook JR, Weisenburger DD, Chan WC, Pierce SK, Staudt LM. (2010). Chronic active B-cell-receptor signalling in diffuse large B-cell lymphoma. Nature 2011:463;88-92. http://www.ncbi.nlm.nih.gov/pubmed/20054396

Dunleavy K, Pittaluga S, Czuczman MS, Dave SS, Wright G, Grant N, Shovlin M, Jaffe ES, Janik JE, Staudt LM, Wilson WH. Differential efficacy of bortezomib plus chemotherapy within molecular subtypes of diffuse large B-cell lymphoma. Blood 2009:113;6069-7. http://www.ncbi.nlm.nih.gov/pubmed/19380866

Hartmann EM, Campo E, Wright G, Lenz G, Salaverria I, Jares P, Xiao W, Braziel RM, Rimsza LM, Chan WC, Weisenburger DD, Delabie J, Jaffe ES, Gascoyne RD, Dave SS, Mueller-Hermelink HK, Staudt LM, Ott G, Bea SM, and Rosenwald A (2010) Pathway discovery in mantle cell lymphoma by integrated analysis of high resolution gene expression and copy number profiling. Blood 2010:116;953-61. http://www.ncbi.nlm.nih.gov/pubmed/20421449

Leich E, Salaverria I, Bea S, Zettl A, Wright G, Moreno V, Gascoyne RD, Chan WC, Braziel RM, Rimsza LM, Weisenburger DD, Delabie J, Jaffe ES, Lister A, Fitzgibbon J, Staudt LM, Hartmann EM, Mueller-Hermelink HK, Campo E, Ott G, Rosenwald A. Follicular lymphomas with and without translocation t(14;18) differ in gene expression profiles and genetic alterations. Blood 2010:144; 826-34. http://www.ncbi.nlm.nih.gov/pubmed/19471018

O'Riain C, O'Shea DM, Yang Y, Le Dieu R, Gribben JG, Summers K, Yeboah-Afari J, Bhaw-Rosun L, Fleischmann C, Mein CA, Crook T, Smith P, Kelly G, Rosenwald A, Ott G, Campo E, Rimsza LM, Smeland EB, Chan WC, Johnson N, Gascoyne RD, Reimer S, Braziel RM, Wright GW, Staudt LM, Lister TA, Fitzgibbon J. Array-based DNA methylation profiling in follicular lymphoma. Leukemia. 2009:23;1858-66. http://www.ncbi.nlm.nih.gov/pubmed/19587707

Wang Y, Ngo VN, Marani M, Yang Y, Wright G, Staudt LM, Downward J Critical role for transcriptional repressor Snail2 in transformation by oncogenic RAS in colorectal carcinoma cells. Oncogene 2010:29;4658-70. http://www.ncbi.nlm.nih.gov/pubmed/20562906

Williams PM, Li R, Johnson NA, Wright G, Heath JD, Gascoyne RD (2010) A novel method of amplification of ffpet-derived rna enables accurate disease classification with microarrays J Mol Diagn 2010:12; 680-86. http://www.ncbi.nlm.nih.gov/pubmed/20688907

Rui L, Emre NC, Kruhlak MJ, Chung HJ, Steidl C, Slack G, Wright GW, Lenz G, Ngo VN, Shaffer AL, Xu W, Zhao H, Yang Y, Lamy L, Davis RE, Xiao W, Powell J, Maloney D, Thomas CJ, Möller P, Rosenwald A, Ott G, Muller-Hermelink HK, Savage K, Connors JM, Rimsza LM, Campo E, Jaffe ES, Delabie J, Smeland EB, Weisenburger DD, Chan WC, Gascoyne RD, Levens D, Staudt LM.

Cooperative epigenetic modulation by cancer amplicon genes. Cancer Cell 2010:18;590-605. http://www.ncbi.nlm.nih.gov/pubmed/21156283

Ngo VN Young RM, Schmitz R, Jhavar S, Xiao WM, Lim KH, Kohlhammer H, Xu WH, Yang YD, Zhao H, Shaffer AL, Romesser P, Wright G, Powell J, Rosenwald A, Muller-Hermelink HK, Ott G, Gascoyne RD, Connors JM, Rimsza LM, Campo E, Jaffe ES, Delabie J, Smeland EB, Fisher RI, Braziel RM, Tubbs RR, Cook JR, Weisenburger DD, Chan WC, Staudt LM. Oncogenically active MYD88 mutations in human lymphoma. Nature 2011:470;115-9. http://www.ncbi.nlm.nih.gov/pubmed/21179087

Rimsza LM, Wright GW, Schwartz M, Chan W, Jaffe E, Gascoyne RD, Campo E, Rosenwald A, Ott G, Cook J, Tubbs RR, Braziel RM, Delabie J, Miller TP, Staudt LM. Classification of diffuse large B cell lymphoma into germinal center and activated B cell subtypes using a nuclease protection assay on paraffin embedded tissues. Clin Cancer Res2011:17;3727-32. http://www.ncbi.nlm.nih.gov/pubmed/21364035