Cancer Genetics and Functional Genomics

Sun CX, Daniel P, Bradshaw G, Shi H, Loi M, Chew N, Parackal S, Tsui V, Liang Y, Koptyra M, Adjumain S, Sun C, Chong WC, Fernando D, Drinkwater C, Tourchi M, Habarakada Dilru, Sooraj D, Carvalho D, Storm PB, Baubet V, Sayles LC, Fernandez E, Nguyen T, Pörksen M, Doan Anh, Crombie D, Panday M, Zhukova N, Dun MD, Ludlow LE, Day B, Stringer B, Neeman N, Rubens J, Hutton Raabe E, Vinci M, Tyrrell V, Fletcher JI, Ekert PG, Dumevska B, Ziegler DS, Tsoli M, Syed Sulaiman NF, Loh AHP, Low SYY, Sweet-Cordero EA, Monje M, Resnick A, Jones C, Downie P, Williams B, Rosenbluh J, Gough D, Cain JE, Firestein R (2023) Generation and Multi-Dimensional Profiling of a Childhood Cancer Cell Line Atlas Defines New Therapeutic Opportunities. Cancer Cell, 41:660-677.e7.

Sooraj D, Sun C, Doan A, Garama DJ, Dannappel MV, Zhu D, Chua H, Mahara S, Wan Hassan W, Croagh D, Prodanovic Z, Gough D, Firestein R. MED12 and BRD4 Cooperate to Sustain Cancer Growth Upon Loss of Mediator Kinase. (in press, Mol Cell).

Wan C, Mahara S, Sun C, Doan A, Chua H, Xu D, Bian J, Li Y, Sooraj D, Cierpicki T, Grembecka J, Firestein R (2021)^. Genome-scale CRISPR-Cas9 screen of Wnt/β-catenin signalling identifies therapeutic targets for Colorectal Cancer. Sci Adv 7:eabf2567.

McCleland ML, Mesh K, Lorenzana E, Chopra VS, Segal E, Watanabe C, Haley B, Mayba O, Yaylaoglu M, Gnad F, Firestein R (2016) CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest 126:639-652.

In this study, we show for the first time that a long non-coding RNA can be used as a biomarker to predict the efficacy to a targeted epigenetic therapeutic.

Storm EE, Durinck S, de Sousa e Melo F, Tremayne J, Kljavin N, Tan C, Ye X, Chiu C, Pham T, Hongo JA, Bainbridge T, Firestein R, Blackwood E, Metcalfe C, Stawiski EW, Yauch RL, Wu Y, de Sauvage FJ (2016) Targeting PTPRK-RSPO3 colon tumours promotes differentiation and loss of stem-cell function. Nature 529:97-100.

This study describes the development of a novel therapeutic antibody targeting colon cancers marked by RSPO3 translocations and Wnt dependence.

Junttila MR, Mao W, Wang X, Wang BE, Pham T, Flygare J, Yu SF, Yee S, Goldenberg D, Fields C, Eastham-Anderson J, Singh M, Vij R, Hongo JA, Firestein R, Schutten M, Flagella K, Polakis P, Polson AG (2015) Targeting LGR5+ cells with an antibody-drug conjugate for the treatment of colon cancer. Sci Transl Med 7:314.

We show here that targeting the LGR5 stem cell marker is efficacious in preclinical models of colon cancer.

Adler AS, McCleland ML, Yee S, Yaylaoglu M, Hussain S, Cosino E, Quinones G, Modrusan Z, Seshagiri S, Torres E, Chopra VS, Haley B, Zhang Z, Blackwood EM, Singh M, Junttila M, Stephan JP, Liu J, Pau G, Fearon ER, Jiang Z, Firestein R (2014). An integrative analysis of colon cancer identifies an essential function for PRPF6 in tumor growth . Genes Dev 28:1068-1084.

This study showed how the tri-snRNP spliceosome regulates tumour growth via preferential splicing of discrete oncogenic variants.

Jaiswal BS, Kljavin NM, Stawiski EW, Chan E, Parikh C, Durinck S, Chaudhuri S, Pujara K, Guillory J, Edgar KA, Janakiraman V, Scholz RP, Bowman KK, Lorenzo M, Li H, Wu J, Yuan W, Peters BA, Kan Z, Stinson J, Mak M, Modrusan Z, Eigenbrot C, Firestein R, Stern HM, Rajalingam K, Schaefer G, Merchant MA, Sliwkowski MX, de Sauvage FJ, Seshagiri S (2013) Oncogenic ERBB3 mutations in Human Cancers. Cancer Cell 23:603-617.

This study reports the identification of ERBB3 activating mutations in colon and gastric cancer and shows how ERBB3 mutant tumours may be targeted with current therapeutic strategies.