Cancer Genomics and Translational Research Laboratory

Welcome to the Cancer Genomics and Translational Research Laboratory.

Our laboratory bridges basic and clinical research to study drug resistance in breast cancer patients. Our research focuses mainly on triple-negative and Her2+ breast cancers, the most aggressive breast cancer subtypes. Through collaborative projects, we also study drug resistance in colon and gastric cancers. Most cancer patients inevitably develop drug resistance at some point during their treatment. Our team makes use of cutting-edge technologies and patient specimens to further understand the mechanisms behind the emergence of resistance; identify novel therapeutic targets as well as biomarkers to monitor recurrence. The ultimate objective of our work is to circumvent resistance and improve cancer therapy to benefit cancer patients.

Our laboratory is part of the Segal Cancer Centre and the Lady Davis
Institute for Medical Research, both affiliated to McGill University in Montreal.
Dr Basik is a surgical scientist at the Lady Davis Institute and an associate professor in the Departments of Surgery and Oncology at McGill University since 2003. He is the Head of the Cancer Genomics and Translational Research Laboratory and the Medical Director of the Inter-disciplinary Breast Cancer Team at the Segal cancer Center at the Jewish General Hospital. Dr. Basik’s laboratory is part of the FRQS Réseau de Cancer axe cancer du sein/ovaire, and as such actively participates in a province-wide breast tumor and plasma banking in breast cancer. His primary research interests are: the investigation of DNA changes in breast and colon cancer the study of mechanisms of resistance to different drugs used in breast and colon cancer, including chemotherapy and targeted therapies; the discovery and validation of tissue and plasma biomarkers predictive of response to treatment. Dr.Basik and his team are working in translational-cancer research, which aims at bridging basic and clinical research for the benefit of cancer patients. The strength of his laboratory is his easy access to clinical patient samples and use of cutting-edge technologies. 
The focus of our research is drug resistance. We make use of human biospecimens collected as part of our extensive biobank, which comprises primary tumors, metastatic tumors and plasma. We have generated pre-clinical models derived from patients’ tumors including a collection of patient derived xenografts from breast, colon and gastric cancer patients. We have also adopted a novel method to establish primary cultures using conditional reprogramming. These pre-clinical in vivo and in vitro tools are currently used in several of our projects.

We make use of genomics tools including gene expression microarrays, whole exome and targeted sequencing, RNA sequencing, copy number analysis and ddPCR technology.

Clinical trials: we have expertise in investigator initiated biopsy driven clinical trials where tumor and blood are collected prior to and during drug treatment. We have expertise in sample collection and processing for downstream molecular profiling and we have developed standard operating procedures to ensure the high quality of biospecimens analyzed. We recently completed the Q-CROC-03 trial, a biopsy driven study to identify molecular markers of drug resistance in triple negative breast cancer, the analyses of these samples are currently part of projects on going in the laboratory.

The projects currently on going in the laboratory include:
• Validation of clinical drug response in PDX and conditionally reprogrammed cells.
• Identification of novel therapeutic targets to overcome drug resistance in triple negative breast cancer.
• Novel treatment modalities for drug resistant HER2+ breast cancers.
• Impact of the microenvironment on drug resistance.
• Identification and validation of biomarkes of drug response and resistance in triple negative breast cancer patients.
• Q-CROC-03- Clinical trial to molecular profile drug resistant triple negative breast cancer.
• Study of tumor suppressor genes (ARID1A and SPEN) in breast cancer.
Lab members:

Adriana Aguilar PhD
Research Associate/Scientific Director

Marguerite Buchanan Msc
Research Assistant/PDX patform

Luca Cavallone PhD
Research Associate/ddPCR expert

Catherine Chabot PhD
Research Associate/Laboratory Manager

Frederic Charbonneau
Clinical research assistant/PMT agent

Emma Fowler
Msc student

Yirui Gui PhD
Post-Doctoral Fellow

Josiane Lafleur Msc
Clinical Research Assistant/Biobank manager

Cathy Lan
Research assistant/Biospecimen handling

Isabelle Sirois PhD
Research Associate/Metabolism and proteomics

Urszula Krmzeien
Clinical Research Assistant/PMT agent

*We are now hiring graduate students

Current research activities have received support from the following sources:
Canadian Institutes for Health Research
Quebec Breast Cancer Foundation
Genome Quebec
Fonds de la Recherche en Santé du Québec
Weekend to End Breast Cancer/JGH Foundation
Cancer Research Society
McPeak-Sirois Group
Exactis Innovation

Special thanks to all our private donors, thanks to your generosity our laboratory has been able to acquire a digital PCR machine to detect tumor DNA in plasma from cancer patients, establish a patient derived xenograft platform and support several research projects in the laboratory.
Selected Publications:

1.SPEN, a new player in primary cilia formation and cell migration in breast cancer.
Légaré S, Chabot C, Basik M. Breast Cancer Res. 2017 Sep 6;19(1):104.

2. Targeted error-suppressed quantification of circulating tumor DNA using semi-degenerate barcoded adapters and biotinylated baits.
Alcaide M, Yu S, Davidson J, Albuquerque M, Bushell K, Fornika D, Arthur S, Grande BM, McNamara S, Tertre MCD, Batist G, Huntsman DG, Cavallone L, Aguilar A, Basik M, Johnson NA, Deyell RJ, Rassekh SR, Morin RD.
Sci Rep. 2017 Sep 5;7(1):10574.

3. Immuno-Matrix-Assisted Laser Desorption/Ionization Assays for Quantifying AKT1 and AKT2 in Breast and Colorectal Cancer Cell Lines and Tumors.
Popp R, Li H, LeBlanc A, Mohammed Y, Aguilar-Mahecha A, Chambers AG, Lan C, Poetz O, Basik M, Batist G, Borchers CH.
Anal Chem. 2017 Oct 3;89(19):10592-10600.

4. Nonoperative Management for Invasive Breast Cancer After Neoadjuvant Systemic Therapy: Conceptual Basis and Fundamental International Feasibility Clinical Trials. Kuerer HM, Vrancken Peeters MTFD, Rea DW, Basik M, De Los Santos J, Heil J. Ann Surg Oncol. 2017 Aug 1.

5. The identification of challenges in tissue collection for biomarker studies: the Q-CROC-03 neoadjuvant breast cancer translational trial experience.
Aguilar-Mahecha A, Lafleur J, Pelmus M, Seguin C, Lan C, Discepola F, Kovacina B, Christodoulopoulos R, Salvucci O, Mihalcioiu C, Roy JA, Robidoux A, Marcus EA, Batist G, Basik M. Mod Pathol. 2017 Jul 28. doi: 10.1038/modpathol.2017.82.

6. Inhibition of EGFR, HER2, and HER3 signaling with AZD8931 in combination with anastrozole as an anticancer approach: Phase II randomized study in women with endocrine-therapy-naïve advanced breast cancer.
Johnston S, Basik M, Hegg R, Lausoontornsiri W, Grzeda L, Clemons M, Dreosti L, Mann H, Stuart M, Cristofanilli M. Breast Cancer Res Treat. 2016 Nov;160(1):91-99.

7. Minireview: The Link Between ERα Corepressors and Histone Deacetylases in Tamoxifen Resistance in Breast Cancer.
Légaré S, Basik M. Mol Endocrinol. 2016 Sep;30(9):965-76. doi: 10.1210/me.2016-1072.

8. PDK1-Dependent Metabolic Reprogramming Dictates Metastatic Potential in Breast Cancer. Dupuy F, Tabariès S, Andrzejewski S, Dong Z, Blagih J, Annis MG, Omeroglu A, Gao D, Leung S, Amir E, Clemons M, Aguilar-Mahecha A, Basik M, Vincent EE, St-Pierre J, Jones RG, Siegel PM.
Cell Metab. 2015 Oct 6;22(4):577-89. doi: 10.1016/j.cmet.2015.08.007.

9. The Estrogen Receptor Cofactor SPEN Functions as a Tumor Suppressor and Candidate Biomarker of Drug Responsiveness in Hormone-Dependent Breast Cancers. Légaré S, Cavallone L, Mamo A, Chabot C, Sirois I, Magliocco A, Klimowicz A, Tonin PN, Buchanan M, Keilty D, Hassan S, Laperrière D, Mader S, Aleynikova O, Basik M. Cancer Res. 2015 Oct 15;75(20):4351-63. doi: 10.1158/0008-5472.CAN-14-3475.

10. A functional in vitro model of heterotypic interactions reveals a role for interferon-positive carcinoma associated fibroblasts in breast cancer.
Hosein AN, Livingstone J, Buchanan M, Reid JF, Hallett M, Basik M.
BMC Cancer. 2015 Mar 15;15:130. doi: 10.1186/s12885-015-1117-0.

11. Glycoproteomic comparison of clinical triple-negative and luminal breast tumors. Hill JJ, Tremblay TL, Fauteux F, Li J, Wang E, Aguilar-Mahecha A, Basik M, O'Connor-McCourt M. J Proteome Res. 2015 Mar 6;14(3):1376-88. doi: 10.1021/pr500987r.

12. Sentinel node biopsy after neoadjuvant chemotherapy in biopsy-proven node-positive breast cancer: the SN FNAC study.
Boileau JF, Poirier B, Basik M, Holloway CM, Gaboury L, Sideris L, Meterissian S, Arnaout A, Brackstone M, McCready DR, Karp SE, Trop I, Lisbona A, Wright FC, Younan RJ, Provencher L, Patocskai E, Omeroglu A, Robidoux A.
J Clin Oncol. 2015 Jan 20;33(3):258-64. doi: 10.1200/JCO.2014.55.7827. Epub 2014 Dec 1.

13. Chromosome-breakage genomic instability and chromothripsis in breast cancer.
Przybytkowski E, Lenkiewicz E, Barrett MT, Klein K, Nabavi S, Greenwood CM, Basik M. BMC Genomics. 2014 Jul 9;15:579. doi: 10.1186/1471-2164-15-579.

14. Testing devices or experimental systems? Cancer clinical trials take the genomic turn. Nelson NC, Keating P, Cambrosio A, Aguilar-Mahecha A, Basik M.
Soc Sci Med. 2014 Jun;111:74-83. doi: 10.1016/j.socscimed.2014.04.008.

15. Imiquimod in the treatment of breast cancer skin metastasis.
Henriques L, Palumbo M, Guay MP, Bahoric B, Basik M, Kavan P, Batist G.
J Clin Oncol. 2014 Mar 10;32(8):e22-5. doi: 10.1200/JCO.2012.46.4883.

16. RSF1 and not cyclin D1 gene amplification may predict lack of benefit from adjuvant tamoxifen in high-risk pre-menopausal women in the MA.12 randomized clinical trial.
Keilty D, Buchanan M, Ntapolias K, Aleynikova O, Tu D, Li X, Shepherd L, Bramwell V, Basik M. PLoS One. 2013 Dec 19;8(12):e81740. doi: 10.1371/journal.pone.0081740.

17. Biopsies: next-generation biospecimens for tailoring therapy.
Basik M, Aguilar-Mahecha A, Rousseau C, Diaz Z, Tejpar S, Spatz A, Greenwood CM, Batist G. Nat Rev Clin Oncol. 2013 Aug;10(8):437-50.
18. Next-generation biobanking of metastases to enable multidimensional molecular profiling in personalized medicine. Diaz Z, Aguilar-Mahecha A, Paquet ER, Basik M, Orain M, Camlioglu E, Constantin A, Benlimame N, Bachvarov D, Jannot G, Simard MJ, Chabot B, Gologan A, Klinck R, Gagnon-Kugler T, Lespérance B, Samson B, Kavan P, Alcindor T, Dalfen R, Lan C, Chabot C, Buchanan M, Przybytkowski E, Qureshi S, Rousseau C, Spatz A, Têtu B, Batist G. Mod Pathol. 2013 Nov;26(11):1413-24. doi: 10.1038/modpathol.2013.81.

19. Ultradense array CGH and discovery of micro-copy number alterations and gene fusions in the cancer genome. Przybytkowski E, Aguilar-Mahecha A, Nabavi S, Tonellato PJ, Basik M. Methods Mol Biol. 2013;973:15-38.

20. Exosomes mediate stromal mobilization of autocrine Wnt-PCP signaling in breast cancer cell migration. Luga V, Zhang L, Viloria-Petit AM, Ogunjimi AA, Inanlou MR, Chiu E, Buchanan M, Hosein AN, Basik M, Wrana JL. Cell. 2012 Dec 21;151(7):1542-56.

21. The effect of pre-analytical variability on the measurement of MRM-MS-based mid- to high-abundance plasma protein biomarkers and a panel of cytokines.
Aguilar-Mahecha A, Kuzyk MA, Domanski D, Borchers CH, Basik M. PLoS One. 2012;7(6).

22. An integrated genomic approach identifies ARID1A as a candidate tumor-suppressor gene in breast cancer. Mamo A, Cavallone L, Tuzmen S, Chabot C, Ferrario C, Hassan S, Edgren H, Kallioniemi O, Aleynikova O, Przybytkowski E, Malcolm K, Mousses S, Tonin PN, Basik M. Oncogene. 2012 Apr 19;31(16):2090-100.

23. The use of ultra-dense array CGH analysis for the discovery of micro-copy number alterations and gene fusions in the cancer genome. Przybytkowski E, Ferrario C, Basik M. BMC Med Genomics. 2011 Jan 27;4:16. doi: 10.1186/1755-8794-4-16.

24. CXCR4 peptide antagonist inhibits primary breast tumor growth, metastasis and enhances the efficacy of anti-VEGF treatment or docetaxel in a transgenic mouse model. Hassan S, Buchanan M, Jahan K, Aguilar-Mahecha A, Gaboury L, Muller WJ, Alsawafi Y, Mourskaia AA, Siegel PM, Salvucci O, Basik M. Int J Cancer. 2011 Jul 1;129(1):225-32.

25. Breast carcinoma-associated fibroblasts rarely contain p53 mutations or chromosomal aberrations. Hosein AN, Wu M, Arcand SL, Lavallée S, Hébert J, Tonin PN, Basik M. Cancer Res. 2010 Jul 15;70(14):5770-7. doi: 10.1158/0008-5472.CAN-10-0673.

26. The influence of tumor-host interactions in the stromal cell-derived factor-1/CXCR4 ligand/receptor axis in determining metastatic risk in breast cancer. Hassan S, Ferrario C, Saragovi U, Quenneville L, Gaboury L, Baccarelli A, Salvucci O, Basik M. Am J Pathol. 2009 Jul;175(1):66-73. doi: 10.2353/ajpath.2009.080948.
Support research at the Lady Davis Institute - Jewish General Hospital