High Resolution Analysis of Follicular Lymphoma Genomes
High resolution analysis follicular lymphoma genomes to discover the genomic rearrangements contributing to development of follicular lymphoma and the additional rearrangements contributing to the progression from follicular lymphoma to diffuse large B cell lymphoma.
|Project Leaders||Marco Marra , Joseph Connors , Randy Gascoyne|
|Project Co-Investigators||Doug Horsman, Jacquie Schein, Martin Krzywinski , Robert Holt , Steven Jones , Carlo Marra|
Genome Science Centre
BC Cancer Agency
University of British Columbia
EZH2 ribbon model
Follicular lymphoma (FL), the most common type of lymphoma, is a cancer of the cells of the immune system. Follicular lymphoma is associated with a specific genome rearrangement where parts of chromosomes 14 and 18 have exchanged. This rearrangement is an initiating event for FL but insufficient without additional mutation events for cancer development. Furthermore, there may be more genome rearrangements to progress from FL to a more aggressive form of the disease, diffuse large B-cell lymphoma. To understand the relationship between rearrangements and disease, this project will identify rearrangements in the FL genome and then analyze the rearrangements to determine their effect on gene structure. Because this is one of the first in depth genome profiling of human cancers, recurrent genomic rearrangements will advance knowledge not only about lymphoma but about cancer in general. Understanding the dysfunctions in lymphoma will permit researchers to develop new diagnostic and prognostic markers and possibly new therapies.
Selected Publications 2007-2010
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. Somatic mutations altering EZH2 (Tyr641) in follicular and diffuse large B-cell lymphomas of germinal-center origin. 2010. Nature Genetics [Epub January 17, 2010 ahead of print].
Birol I, Jackman S, Nielsen C, Qian J, Varhol R, Stazyk G, Zhao YJ, Hirst M, Schein J, Horsman D, Connors J, Gascoyne R, Marra M, Jones S. (2009) De novo Transcriptome Assembly with AbySS. Bioinformatics [epub ahead of print Jun 15, 2009]PMID: 19528083
Simpson JT, Wong K, Jackman SD, Schein JE, Jones SJM, and Birol B. (2009) ABySS: A parallel assembler for short read sequence data. Genome Research 19(6), 1117-23. [Epub 2009 Feb 27] doi: 10.1101/gr.089532.108 PMID: 19251739
Cheung KJ, Shah SP, Steidl C, Johnson N, Relander T, Telenius A, Lai B, Murphy KP, Lam W, Al-Tourah AJ, Connors JM, Ng RT, Gascoyne RD, Horsman DE. (2009) Genome-wide profiling of follicular lymphoma by array comparative genomic hybridization reveals prognostically significant DNA copy number imbalances. Blood 114(1),137-48. [Epub 2008 Aug 14] doi:10.1182/blood-2008-02-140616 PMID: 18703704
Krzywinski M, Bosdet I, Mathewson C, Wye N, Brebner J, Chiu R, Corbett R, Field M, Lee D, Pugh T, Volik S, Siddiqui A, Jones S, Schein J, Collins C, Marra MA. (2007) A BAC clone fingerprinting approach to the detection of human genome rearrangements.Genome Biol. 8(10), R224. PMID: 17953769 doi:10.1186/gb-2007-8-10-r224
To inquire about obtaining BAC clones, please contact Ms. Jacquie Schein
For all other project-related inquires please contact:
Adrienne Drobnies, Project Manager
Genome Sciences Centre, BC Cancer Agency
Phone: 604-707-5900 x 5436
EZH2 models showing how variation in protein sequence effects 3D structure.