How did that happen?!
The first half of 2011 has been a busy and exciting time for the Department of Breast and Molecular Oncology; our scientists have published papers, been awarded grants, and travelled all over the world to speak about their work at conferences. As the summer solstice approaches, it seems like a good time to reflect on the highlights of the year so far!
Papers published by the Aparicio lab have been in the news a couple of times this year. The first featured manuscript was published in February in collaboration with British researchers; the team found that the over-activation of a gene called ZNF703 is involved in the development of some breast cancers1. ZNF703 is over-activated in around one third of breast tumours that fall into the aggressive luminal B category (and in a much smaller percentage of other types of breast tumour), and causes cancer-like changes in cells grown in culture. This discovery – the first new breast cancer oncogene to be identified in five years – was featured by various media outlets, including the BBC. More recently, the lab’s collaboration with Dr. Connie Eaves of the BC Cancer Agency’s Terry Fox Laboratory was featured by the Vancouver Sun. The work in question involved implanting a single human breast stem cell into a mouse, and allowing it to develop a functional, milk-producing, human mammary gland. Now that this procedure has been successfully carried out for the first time, the team are using their novel mouse model to study the role of breast stem cells in the development of cancer.
The Bénard lab has also been in the news this year. In collaboration with the TRIUMF lab at the University of British Columbia, the team have been awarded $6 million by the Canadian government to develop alternative radioactive isotopes for use in medical imaging. The global supply of medical isotopes is under threat due to the aging of current facilities such as the Chalk River nuclear reactor in Ontario, and Dr. Bénard’s efforts to develop sustainable replacements have been featured in the Globe and Mail as well as in the local media, such as this report by Global BC.
Meanwhile, the Huntsman lab is continuing their efforts to better understand the causes of ovarian and uterine cancer. Having made a big splash last year by identifying mutations in the ARID1A gene in ovarian clear cell and endometrioid carcinomas2, the team have gone on to look for similar abnormalities in other types of cancer. They have now shown that the loss of this gene is very rare in other cancers, but common in endometrioid ovarian cancers, where loss of ARID1A seems to occur very early on in the development of some tumours3. In a related study, the team worked with the Shah lab to identify mutations in a gene called PPP2R1A in high-grade serous endometrial tumours, and in endometrioid and clear cell carcinomas of the ovary4. These studies demonstrate the power of the cancer genome sequencing approach used by the Department of Breast and Molecular Oncology, and are opening up new avenues of investigation into the causes and treatment of ovarian and uterine cancer.
The Shah lab have, as always, played a major role in many of the studies published by the Department this year; their expertise in the analysis of cancer genome sequencing data is absolutely crucial to our efforts to make sense of the flood of information we generate. The team have also helped other similar labs around the world, by developing and releasing analysis tools such as the recently published deFUSE algorithm5. deFUSE is a novel computational method that identifies fusions between two or more genes; such fusions are common in some kinds of cancer, and can cause havoc in human cells as they alter the function of one or both fusion partners. The Shah lab have already used deFUSE to identify the first gene fusions ever to be found in ovarian cancer. Dr. Sohrab Shah also took part in The Canadian Breast Cancer Foundation‘s Breast Health Speaker series in March; he introduced an audience at the West Vancouver Community Centre to the power of genome sequencing in breast cancer research.
The Sorensen lab also had reason to celebrate this year, as Genome Canada and Genome BC announced that Dr. Poul Sorensen will lead the newly formed Canadian Pediatric Cancer Genome Consortium. This group of researchers will investigate how children’s cancers develop and then spread, with a focus on osteosarcoma (a bone cancer) and several types of pediatric brain cancer (namely medulloblastoma, atypical rhabdoid teratoid tumour, and glioblastoma). By pooling their resources and expertise, and harnessing the immense power of cancer genome sequencing, the team expect to make important discoveries that will quickly move into tests of new drugs for childhood cancers.
I hope you agree that we’ve made good progress so far in 2011! Naturally, though, we refuse to rest on our laurels, and our labs and offices are a hive of activity as all teams continue to follow up on the findings described above and on their numerous other projects.
Stay tuned for more exciting updates, coming soon!
1) Holland D, Burleigh A, Git A, Goldgraben MA, Perez-Mancera PA, Chin SF, Hurtado A, Bruna A, Ali R, Greenwood W, Dunning MJ, Samarajiwa S, Menon S, Rueda OM, Lynch AG, McKinney S, Ellis IO, Eaves CJ, Carroll JS, Curtis C, Aparicio S, Caldas C. ZNF703 is a common Luminal B breast cancer oncogene that differentially regulates luminal and basal progenitors in human mammary epithelium. EMBO Mol Med 2011: 3:1–14
2) Wiegand KC, Shah SP, Al-Agha OM, Zhao Y, Tse K, Zeng T, Senz J, McConechy MK, Anglesio MS, Kalloger SE, Yang W, Heravi-Moussavi A, Giuliany R, Chow C, Fee J, Zayed A, Prentice L, Melnyk N, Turashvili G, Delaney AD, Madore J, Yip S, McPherson AW, Ha G, Bell L, Fereday S, Tam A, Galletta L, Tonin PN, Provencher D, Miller D, Jones SJM, Moore RA, Morin GB, Oloumi A, Boyd N, Aparicio SA, Shih T-M, Mes-Masson A-M, Bowtell DD, Hirst M, Gilks B, Marra MA, Huntsman DG. ARID1A Mutations in Endometriosis-Associated Ovarian Carcinomas. N Engl J Med 2010: 363(16):1532-43
3) Wiegand KC, Lee AF, Al-Agha OM, Chow C, Kalloger SE, Scott DW, Steidl C, Wiseman SM, Gascoyne RD, Gilks B, Huntsman DG. Loss of BAF250a (ARID1A) is frequent in high-grade endometrial carcinomas. J Pathol. 2011: 224(3): 328–333
4) McConechy MK, Anglesio MS, Kalloger SE, Yang W, Senz J, Chow C, Heravi-Moussavi A, Morin GB, Mes-Masson AM; Australian Ovarian Cancer Study Group, Carey MS, McAlpine JN, Kwon JS, Prentice LM, Boyd N, Shah SP, Gilks CB, Huntsman DG. Subtype-specific mutation of PPP2R1A in endometrial and ovarian carcinomas. J Pathol. 2011:223(5): 567-573.
5) McPherson A, Hormozdiari F, Zayed A, Giuliany R, Ha G, Sun MG, Griffith M, Heravi Moussavi A, Senz J, Melnyk N, Pacheco M, Marra MA, Hirst M, Nielsen TO, Sahinalp SC, Huntsman D, Shah SP. deFuse: An Algorithm for Gene Fusion Discovery in Tumor RNA-Seq Data. PLoS Comput Biol. 2011: 7(5):e1001138