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