Adam Shlien

Dr. Adam Shlien is Associate Director, Translation Genetics in the Department of Paediatric Laboratory Medicine at the Hospital for Sick Children, and Scientist in the SickKids Research Institute.

His research uses the tools of modern sequence-based genomics to discover the mutations that are present in the genomes of paediatric cancer patients, and to understand how these mutations alter the somatic transcriptome.

Dr. Shlien received his PhD from the University of Toronto for the study of copy number variation and cancer susceptibility.

He continued his training as a Postdoctoral Fellow at the Wellcome Trust Sanger Institute, with Sir Mike Stratton and Dr Peter Campbell, where he developed methods to understand the transcriptional consequences of point mutation in cancer.             

Research Synopsis

All cancers carry somatic mutations.

The complete repertoire of mutations in each tumour genome is unique, and when analysed as a whole can reveal the evolutionary history of a patient’s cancer, including the DNA damage processes that have gone awry and the subclonal architecture of the tumour. 

A subset of these mutations are “drivers” as they are causally implicated in oncogenesis and confer a selective advantage.

My group at the Hospital for Sick Children is interested in discovering the mutations that are present in the genomes of paediatric cancer patients, and to understand how drivers mutations alter the somatic transcriptome.

My lab is working on a number of projects, whose aims include:

1. Understanding the transcriptional consequences of somatic mutation in cancer;
2. Understanding the timing and processes that give rise to mutations in pediatric cancers, with a particular emphasis on sarcomas;
3. Developing novel informatics methods for the analysis of thousands of sequenced cancer specimens with an emphasis on integrative analyses;
4. Incorporating next-generation sequencing into routine oncological practice.

Selected Publications

Processed pseudogenes acquired somatically during cancer development. Cooke SL, Shlien A, Marshall J, Pipinikas CP, Martincorena I, Tubio JM, Li Y, Menzies A, Mudie L, Ramakrishna M, Yates L, Davies H, Bolli N, Bignell GR, Tarpey PS, Behjati S, Nik-Zainal S, Papaemmanuil E, Teixeira VH, Raine K, O'Meara S, Dodoran MS, Teague JW, Butler AP, Iacobuzio-Donahue C, Santarius T, Grundy RG, Malkin D, Greaves M, Munshi N, Flanagan AM, Bowtell D, Martin S, Larsimont D, Reis-Filho JS, Boussioutas A, Taylor JA, Hayes ND, Janes SM, Futreal PA, Stratton MR, McDermott U, Campbell PJ; ICGC Breast Cancer Group. Nat Commun. 2014 Apr 9;5:3644. doi: 10.1038/ncomms4644.

A proteomic chronology of gene expression through the cell cycle in human myeloid leukemia cells. Ly T, Ahmad Y, Shlien A, Soroka D, Mills A, Emanuele MJ, Stratton MR, Lamond AI. Elife. 2014 Jan 1;3:e01630. doi: 10.7554/eLife.01630.

Mutational processes molding the genomes of 21 breast cancers. Nik-Zainal S, Alexandrov LB, Wedge DC, Van Loo P, Greenman CD, Raine K, Jones D, Hinton J, Marshall J, Stebbings LA, Menzies A, Martin S, Leung K, Chen L, Leroy C, Ramakrishna M, Rance R, Lau KW, Mudie LJ, Varela I, McBride DJ, Bignell GR, Cooke SL, Shlien A, Gamble J, Whitmore I, Maddison M, Tarpey PS, Davies HR, Papaemmanuil E, Stephens PJ, McLaren S, Butler AP, Teague JW, Jönsson G, Garber JE, Silver D, Miron P, Fatima A, Boyault S, Langerød A, Tutt A, Martens JW, Aparicio SA, Borg Å, Salomon AV, Thomas G, Børresen-Dale AL, Richardson AL, Neuberger MS, Futreal PA, Campbell PJ, Stratton MR; Breast Cancer Working Group of the International Cancer Genome Consortium. Cell. 2012 May 25;149(5):979-93. doi: 10.1016/j.cell.2012.04.024. Epub 2012 May 17.

The life history of 21 breast cancers. Nik-Zainal S, Van Loo P, Wedge DC, Alexandrov LB, Greenman CD, Lau KW, Raine K, Jones D, Marshall J, Ramakrishna M, Shlien A, Cooke SL, Hinton J, Menzies A, Stebbings LA, Leroy C, Jia M, Rance R, Mudie LJ, Gamble SJ, Stephens PJ, McLaren S, Tarpey PS, Papaemmanuil E, Davies HR, Varela I, McBride DJ, Bignell GR, Leung K, Butler AP, Teague JW, Martin S, Jönsson G, Mariani O, Boyault S, Miron P, Fatima A, Langerød A, Aparicio SA, Tutt A, Sieuwerts AM, Borg Å, Thomas G, Salomon AV, Richardson AL, Børresen-Dale AL, Futreal PA, Stratton MR, Campbell PJ; Breast Cancer Working Group of the International Cancer Genome Consortium. Cell. 2012 May 25;149(5):994-1007. doi: 10.1016/j.cell.2012.04.023. Epub 2012 May 17

A common molecular mechanism underlies two phenotypically distinct 17p13.1 microdeletion syndromes. Shlien A, Baskin B, Achatz MI, Stavropoulos DJ, Nichols KE, Hudgins L, Morel CF, Adam MP, Zhukova N, Rotin L, Novokmet A, Druker H, Shago M, Ray PN, Hainaut P, Malkin D. Am J Hum Genet. 2010 Nov 12;87(5):631-42. doi: 10.1016/j.ajhg.2010.10.007.

TP53 alterations determine clinical subgroups and survival of patients with choroid plexus tumors. Tabori U, Shlien A, Baskin B, Levitt S, Ray P, Alon N, Hawkins C, Bouffet E, Pienkowska M, Lafay-Cousin L, Gozali A, Zhukova N, Shane L, Gonzalez I, Finlay J, Malkin D. J Clin Oncol. 2010 Apr 20;28(12):1995-2001. doi: 10.1200/JCO.2009.26.8169. Epub 2010 Mar 22.

Copy number variations and cancer susceptibility. Shlien A, Malkin D. Curr Opin Oncol. 2010 Jan;22(1):55-63. doi: 10.1097/CCO.0b013e328333dca4. Review.

Copy number variations and cancer. Shlien A, Malkin D. Genome Med. 2009 Jun 16;1(6):62. doi: 10.1186/gm62.

Excessive genomic DNA copy number variation in the Li-Fraumeni cancer predisposition syndrome. Shlien A, Tabori U, Marshall CR, Pienkowska M, Feuk L, Novokmet A, Nanda S, Druker H, Scherer SW, Malkin D. Proc Natl Acad Sci U S A. 2008 Aug 12;105(32):11264-9. doi: 10.1073/pnas.0802970105. Epub 2008 Aug 6.

Appointments

Associate Director, Translation Genetics, Department of Paediatric Laboratory Medicine, Hospital for Sick Children