Professor Ian Tomlinson PhD, FRCPath, FMedSci

Professor Ian Tomlinson

Institute of Cancer and Genomic Sciences
Director of the Institute of Cancer and Genomic Sciences

Contact details

Institute of Cancer and Genomic Sciences
University of Birmingham
B15 2TT

Professor Ian Tomlinson was appointed Director of the Institute of Cancer and Genomic Sciences in the Summer of 2017. His research interests are centred on the biology of colorectal cancer, genetic predisposition to cancer, cancer prevention and cancer evolution. Professor Tomlinson's work encompasses both patients and model systems, but is almost always related to human disease.

In 2019 Professor Tomlinson was elected as a Fellow of the Royal Society. 


  • EMBO member, 2016
  • Fellow of the Academy of Medical Sciences, 2009
  • FRCPath, 1998
  • BM, BCh in Clinical Medicine, University of Oxford, 1992
  • PhD, University of Cambridge, 1988
  • MA, University of Cambridge, 1985


Professor Ian Tomlinson is a Professor of Cancer and Genomic Sciences and Honorary Consultant in Genetics and Molecular Pathology. His scientific career began in population genetics and evolution, before moving on to cancer genetics after his medical training. He has worked and led research groups at Cancer Research UK London Research Institute, St Mark’s Hospital, Bart’s and the London Medical School, and the University of Oxford. He has pursued a largely research-based career, with highly focussed clinical roles.

Professor Tomlinson is particularly interested in combining research across disciplines, such as human and mouse genetics, and mathematics and molecular oncology. His research has included identification of several Mendelian cancer predisposition genes (GREM1, POLE, POLD1, SMAD4, STK11, FH), coupled with delineation of the clinical features of these conditions and the introduction of genetic testing into clinical practice. He has also co-led genome-wide association studies in colorectal cancer, endometrial cancer and oesophageal cancer, resulting in the identification of ~60 polymorphisms associated with the risk of cancers and their benign precursor lesions. His laboratory have developed and characterised several animal models of human cancer predisposition genes (Apc, Fbxw7, Fh, Idh1, Grem1), providing new insights into the pathobiology of the corresponding human diseases. His work has also identified new models of cancer evolution, including laboratory and mathematical studies of the roles of mutation and selection in carcinogenesis. 


Professor Tomlinson has supervised over 30 PhD and MD students, of whom over a fifth have gone to run their own research groups, and others have senior clinical posts.

Applications are always welcomed within the broad research areas described below (cancer predisposition, functional studies and mouse models of cancer, and cancer evolution).


We continue to search for cancer driver genes, focussing on gastrointestinal cancer and other malignancies with a shared genetic basis. This has led to the identification of 9 common polymorphisms (SNPs) for Barrett’s oesophagus and oesophageal cancer and 8 endometrial cancer risk SNPs. We have recently identified a further 17 colorectal cancer SNPs. Whole-genome sequencing has been performed on ~500 colorectal cancer patients and these data have already identified new Mendelian cancer predisposition genes, POLE and POLD1, and provided critical evidence proving the role of RNF43. Further analysis is in progress.

We have pursued functional studies of colorectal cancer predisposition genes that we have identified, specifically the bone morphogenetic protein signalling antagonist GREM1 and POLE and POLD1. A mouse model over-expressing Grem1 has identified downstream mechanisms of tumorigenesis driven by stem cell expansion. GREM1 is activated by a large non-coding mutation and work to determine how this 40kb mutation leads to gene over-expression and shift from mesenchyme to epithelium is progressing.

POLE/POLD1 work involves characterising proofreading domain mutations in germ line and sporadic cancers. These mutations are incorporated into genetic testing worldwide and into clinical trials, because they mark very good cancer prognosis and potentially, response to immune checkpoint inhibitors, as they cause an ultramutator phenotype.

We have developed a mouse model of glioma driven by isocitrate dehydrogenase mutations. This has shown an expansion of stem cell numbers, Wnt activation and DNA methylation as probable drivers of gliomagenesis (further details in main application).

Cancer evolution studies have focussed on genomic changes induced by chemoradiotherapy in the neo-adjuvant setting, specifically in oesophageal and rectal cancers. These have demonstrated a variety of behaviours, including evolutionary bottlenecks and fluctuations in clonal composition, including cell populations with major driver mutations. Further work has performed multi-region sequencing of benign and malignant colorectal tumours, showing different tumour dynamics at different stages of tumorigenesis.

Other activities

Current Roles

  •  Cancer Research UK Science Committee, 2017-
  •  Academy of Medical Sciences Fellowship Committee, 2016-
  •  Bowel Cancer UK Scientific Committee, 2016-
  •  Journal of Pathology Editorial Board, 2014-
  •  Scientific Reports Editorial Board, 2017-
  •  EU ERC grants panels, 2015-


Over 500 peer-reviewed publications, including the following selected:

Functional genetics

1. Bardella, C., Al-Dalahmah, O., Krell, D., Brazauskas, P., Al-Qahtani, K., Tomkova, M., Adam, J., Serres, S., Lockstone, H., Freeman-Mills, L., 13 others and Tomlinson, I. Expression of Idh1R132H in the murine subventricular zone stem cell niche recapitulates features of early gliomagenesis. Cancer Cell, 2016. 30: 578-594.

 The first mouse model of isocitrate dehydrogenase-driven brain tumorigenesis, showing increased stem cell numbers, aberrant migration and invasion, Wnt pathway activation and increased DNA methylation.

 2. Davis, H., Irshad, S., Bansal, M., Rafferty, H., Boitsova, T., Bardella, C., Jaeger, E., Lewis, A., Freeman-Mills, L., Giner, F.C., 14 others, Tomlinson, I.* and Leedham, S.J.* Aberrant epithelial GREM1 expression initiates colonic tumorigenesis from cells outside the stem cell niche. Nat Med, 2015. 21: 62-70.

Mouse model of the human disease hereditary mixed polyposis syndrome, showing acquisition of stem cell properties by cells outside the niche, leading to clonogenic growth and probable tumour formation.

3. Lewis, A., Freeman-Mills, L., de la Calle-Mustienes, E., Giráldez-Pérez, R.M., Davis, H., Jaeger, E., Becker, M., Hubner, N.C., Nguyen, L.N., Zeron-Medina, J., 5 others and Tomlinson I. A polymorphic enhancer near GREM1 influences bowel cancer risk through differential CDX2 and TCF7L2 binding. Cell Rep, 2014. 8: 983-990.

4. Pollard, P.J., Spencer-Dene, B., Shukla, D., Howarth, K., Nye, E., El-Bahrawy, M., Deheragoda, M., Joannou, M., McDonald, S., Martin, A., 6 others and Tomlinson, I. Targeted inactivation of Fh1 causes proliferative renal cyst development and activation of the hypoxia pathway. Cancer Cell, 2007. 11: 311-9.

Mouse model of human disease hereditary leiomyomatosis and papillary renal cell cancer, showing accumualtion of Krebs cycle intermediates secondary to fumarate hydratase mutations and proliferative renal lesions with HIF prolyl hydroxylase inhibition. Led to enhanced interests in cancer metabolism driver genes, including that on isocitrate dehydrogenase.

Cancer Evolution

1. Lamlum, H., Ilyas, M., Rowan, A., Clark, S., Johnson, V., Bell, J., Frayling, I., Efstathiou, J., Pack, K., Payne, S., Roylance, R., Gorman, P., Sheer, D., Neale, K., Phillips, R., Talbot, I., Bodmer, W. and Tomlinson, I., The type of somatic mutation at APC in familial adenomatous polyposis is determined by the site of the germline mutation: a new facet to Knudson's 'two-hit' hypothesis. Nat Med, 1999. 5: 1071-5.

Provided some of the first evidence for windows of selection in tumorigenesis, specifically that there exists an optimum, intermediate ("just right") level of Wnt signalling for colorectal tumorigenesis, reflected in mutation patterns in the APC gene.

2. Pollard, P., Deheragoda, M., Segditsas, S., Lewis, A., Rowan, A., Howarth, K., Willis, L., Nye, E., McCart, A., Mandir, N., 8 others and Tomlinson, I. The Apc 1322T mouse develops severe polyposis associated with submaximal nuclear beta-catenin expression. Gastroenterology, 2009. 136: 2204-2213.

Development of a mouse to test the findings of Lamlum et al, confirming the "just right" model in a controlled setting.

3. Hornsby, C., Page, K.M. and Tomlinson, I., What can we learn from the population incidence of cancer? Armitage and Doll revisited. Lancet Oncol, 2007. 8: 1030-8.

Demonstration that cancer evolution may be a "multi-hit" process involving tens of driver rmutations despite the age-dependent incidence statistics originally used by Armitage and Doll to predict a handful of driver mutations in many of the common cancers.

4. Tomlinson, I. and Bodmer, W.F., Failure of programmed cell death and differentiation as causes of tumors: some simple mathematical models. Proc Natl Acad Sci USA, 1995. 92: 11130-4.

Models of colorectal cancer evolution showing that the dynamics of the colorectal crypt do not always favour unlimited tumour growth, but instead that growth to limited tumour size is often likely.

Genetic predisposition to cancer

 1. Cheng, T.H., Thompson, D.J., O'Mara, T.A., Painter, J.N., Glubb, D.M., Flach, S., Lewis, A., French, J.D., Freeman-Mills, L., Church, D., 54 others, Easton, D.F.*, Tomlinson, I.* and Spurdle, A.B.* (2016). Five endometrial cancer risk loci identified through genome-wide association analysis. Nat Genet, 2016. 48: 667-674.

Combined discovery of endometrial cancer risk SNPs through GWAS and multi-method assessment to identify and characterise the functional variation at one of these SNPs near the KLF5 locus.

2. Palles, C., Cazier, J.B., Howarth, K.M., Domingo, E., Jones, A.M., Broderick, P., Kemp, Z., Spain, S.L., Almeida, E.G., Salguero, I, 28 others, Houlston, R.S. and Tomlinson I. Germline mutations affecting the proofreading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas. Nat Genet, 2013. 45: 136-144

Use of genome sequencing to discover germline mutations in DNA polymerases epsilon and delta that lead to a Mendelian predisposition to colorectal cancer.

 3. Jaeger, E., Leedham, S., Lewis, A., Segditsas, S., Becker, M., Cuadrado, P., Davis, H. Kaur, K., Heinimann, K., Howarth, K. East, J., Taylor, J., Thomas H., and Tomlinson, I. Hereditary mixed polyposis syndrome is caused by a 40-kb upstream duplication that leads to increased and ectopic expression of the BMP antagonist GREM1. Nat Genet, 2012. 44: 699-703.

Identification of an unusual non-coding 40kb duplication containing regulatory elements for the Gremlin1 gene that leads to a Mendelian colorectal cancer syndrome.

4. Dunlop, M.G.*, Dobbins, S.E., Farrington, S.M., Jones, A.M., Palles, C., Whiffin, N., Tenesa, A., Spain, S., Broderick, P., 22 others, Tomlinson, I.* and Houlston, R.S.* Common variation near CDKN1A, POLD3 and SHROOM2 influences colorectal cancer risk. Nat Genet, 2012. 44: 770-776.

5. Su, Z., Gay, L.J., Strange, A., Palles, C., Band, G., Whiteman, D.C., Lescai, F., Langford, C., Nanji, M., Edkins, S., 84 others, Tomlinson, I.*, Donnelly, P.* and Jankowski, J.A.* Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett's esophagus. Nat Genet, 2012. 44: 1131-1136.

6. Houlston, R. S.*, Cheadle, J., Dobbins, S. E., Tenesa, A., Jones, A. M., Howarth, K., Spain, S. L., Broderick, P., Domingo, E., Farrington, S., 35 others, Dunlop, M. G.* and Tomlinson, I.*. Meta-analysis of three genome-wide association studies identifies susceptibility loci for colorectal cancer at 1q41, 3q26.2, 12q13.13 and 20q13.33. Nat Genet, 2010. 42: 973-977.

7. Tomlinson, I.*, Webb, E., Carvajal-Carmona, L., Broderick, P., Howarth, K., Pittman, A.M., Spain, S., Lubbe, S., Walther, A., 44 others and Houlston, R.S.*. A genome-wide association study identifies colorectal cancer susceptibility loci on chromosomes 10p14 and 8q23.3. Nat Genet, 2008. 40: 623-630.

8. Jaeger, E., Webb, E., Howarth, K., Carvajal-Carmona, L., Rowan, A., Broderick, P., Walther, A., Spain, S., Pittman, A., Kemp, Z., 14 others, Houlston, R.* and Tomlinson, I.* Common genetic variants at the CRAC1 (HMPS) locus on chromosome 15q13.3 influence colorectal cancer risk. Nat Genet, 2008. 40: 26-8.

Discovery that the Gremlin1 gene not only predisposes to mixed poylposis syndrome but also harbours common variants that influence colorectal cancer risk in the general population.

9. Tomlinson, I.*, Webb, E., Carvajal-Carmona, L., Broderick, P., Kemp, Z., Spain, S., Penegar, S., Chandler, I., Gorman, M., Wood, W., 23 others and Houlston, R.* A genome-wide association scan of tag SNPs identifies a susceptibility variant for colorectal cancer at 8q24.21. Nat Genet, 2007. 39: 984-8.

10. Sieber, O.M., Lipton, L., Crabtree, M., Heinimann, K., Fidalgo, P., Phillips, R.K., Bisgaard, M.L., Orntoft, T.F., Aaltonen, L.A., Hodgson, S.V., Thomas, H.J. and Tomlinson, I., Multiple colorectal adenomas, classic adenomatous polyposis, and germ-line mutations in MYH. N Engl J Med, 2003. 348: 791-9.

11. Tomlinson, I., Alam, N.A., Rowan, A.J., Barclay, E., Jaeger, E.E., Kelsell, D., Leigh, I., Gorman, P., Lamlum, H., Rahman, S., Roylance, R.R., 29 others, Houlston, R.S. and Aaltonen, L.A., Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer. Nat Genet, 2002. 30: 406-10.

Identification of mutations in the TCA cycle gene, fumarate hydratase, as the cause of a previously unappreciated Mendelian cancer syndrome.

12. Hemminki, A., Markie, D., Tomlinson, I., Avizienyte, E., Roth, S., Loukola, A., Bignell, G., Warren, W., Aminoff, M., Hoglund, P., 11 others and Aaltonen, L.A., A serine/threonine kinase gene defective in Peutz-Jeghers syndrome. Nature, 1998. 391: 184-7.

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Biology of colorectal cancer, genetic predisposition to cancer, cancer prevention and cancer evolution.