Sequencing for Discovery of Candidate Mutations in Lymphoma Transcriptomes
This project involves identifying and characterizing the range of mutations found in lymphoma tumours. Once identified, specific mutations may be shown to effect or be associated with response to treatment, patient outcome and survival, or be useful as a target for anti-cancer drug development.
|Project Leaders||Marco Marra|
|Project Co-Investigators||Steven Jones , Martin Hirst , Joseph Connors , Randy Gascoyne|
We will collect fresh-frozen tumour biopsy material and DNA from normal non-cancerous tissues from a group of patients with diffuse large B cell lymphoma (DBCL). Each sample of cells will be subjected to genomic, cytogenetic and functional analyses involving:
- A whole transcriptome “shotgun” approach that has the potential to identify both point mutations and novel transcript structures, such as transcriptional fusions that might arise as a consequence of genome rearrangements
- Computational identification of candidate mutations
- Karyotypic and more detailed cytogenetic characterization using FISH, aCGH and SNP CHIP analyses
- Validation studies utilizing matched normal samples
This research will result in a list of somatic mutations, both large and small scale, that will be likely suspects in driving the development of lymphoid cancers and in the progression of the disease.
Detail of DNA sequence showing 2 common mutations associated with DLBCL tumor development.
Publications by our Research Team:
Recurrent targets of aberrant somatic hypermutation in lymphoma. 2012. Oncotarget. 2012 Oct 12. [Epub ahead of print]. Khodabakhshi AH, Morin RD, Fejes AP, Mungall AJ, Mungall KL, Bolger-Munro M, Johnson NA, Connors JM, Gascoyne RD, Marra MA, Birol I, Jones SJ.
Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma. 2011. Nature (Published online 27 July 2011; doi:10.1038/nature10351) Ryan D. Morin, Maria Mendez-Lago, Andrew J. Mungall, Rodrigo Goya, Karen L. Mungall, Richard D. Corbett, Nathalie A. Johnson, Tesa M. Severson, Readman Chiu, Matthew Field, Shaun Jackman, Martin Krzywinski, David W. Scott, Diane L. Trinh, Jessica Tamura-Wells, Sa Li, Marlo R. Firme, Sanja Rogic, Malachi Griffith, Susanna Chan, Oleksandr Yakovenko, Irmtraud M. Meyer, Eric Y. Zhao, Duane Smailus, Michelle Moksa, Suganthi Chittaranjan, Lisa Rimsza, Angela Brooks-Wilson, John J. Spinelli, Susana Ben-Neriah, Barbara Meissner, Bruce Woolcock, Merrill Boyle, Helen McDonald, Angela Tam, Yongjun Zhao, Allen Delaney, Thomas Zeng, Kane Tse, Yaron Butterfield, Inanç Birol, Rob Holt, Jacqueline Schein, Douglas E. Horsman, Richard Moore, Steven J. M. Jones, Joseph M. Connors, Martin Hirst, Randy D. Gascoyne & Marco A. Marra
Somatic mutations altering EZH2 (Tyr641) in follicular and diffuse large B-cell lymphomas of germinal-center origin. 2010. Nature Genetics 42(2):181-185. Morin RD, Johnson NA, Severson TM, Mungall AJ, An J, Goya R, Paul JE, Boyle M, Woolcock BW, Kuchenbauer F, Yap D, Humphries RK, Griffith OL, Shah S, Zhu H, Kimbara M, Shashkin P, Charlot JF, Tcherpakov M, Corbett R, Tam A, Varhol R, Smailus D, Moksa M, Zhao Y, Delaney A, Qian H, Birol I, Schein J, Moore R, Holt R, Horsman DE, Connors JM, Jones S, Aparicio S, Hirst M, Gascoyne RD, Marra MA.
For all project related inquires please contact:
Karen Novik, Project Manager
Genome Sciences Centre, BC Cancer Agency
Phone: 604-675-8000 x 7983