This seminar of Prof. Sir Nick Wright is cancelled.

This seminar of Prof. Sir Nick Wright is cancelled.

9 July 2015 16:00 hrs. - 17:30 hrs.
Tuinzaal, route 706

Professor Sir Nicholas Wright, Centre for Tumour Biology, Barts Cancer Institute, Queen Mary University of London, London, UK


Prof. Iris Nagtegaal, Chair of Gastrointestinal Pathology, Theme leader Tumors of the Digestive Tract, Radboudumc

09-07-2015 16:00:0009-07-2015 17:30:00Europe/AmsterdamCancelled Tuinzaal, route

Remarks / more information:

Due to personal circumstances the seminar of Prof. Sir Nick Wright is cancelled.



16:00: Seminar

17:00: College tour with Nick Wright

17:30: Research Café

We are generally used to the idea that tumors, especially tumors such as colorectal, gastric and esophageal carcinomas, progress gradually but inexorably as they steadily accumulate the mutational burden which establishes the invasive, and finally the metastatic phenotype.  This is the traditional clonal selection hypothesis, in which sequential mutations produce fitter clones able to sweep through the population, albeit slowly.   Indeed, our clinical screening and surveillance programs for colorectal carcinoma, for colitis-associated cancer, and, in some countries, for Barrett’s esophagus are designed around such a slowly progressive model.  Similarly, we are depressed, from a clinical viewpoint, about the extreme tumor heterogeneity we find, which lies at the heart of failure of many cancer treatments, as it expedites the emergence of resistance to targeted therapy. Again we rely in on the clonal selection model to explain the complex spatial and temporal process of tumor progression. 

However, recent studies have cast doubt on this hypothesis: in colorectal adenomas, in Barrett’s metaplasia, and inflammatory bowel disease – all established as stereotypical premalignant phases which precede colorectal and esophageal carcinomas - the prevailing state is one of evolutionary stasis (1-3): clonal evolution occurs but there are few clonal contractions and expansions, and genetic (and? phenotypic) diversity remains at similar levels. However, in those individuals who progress, evolution is rapid, often within a few years (3,4). An alternative model, which fits these observations, suggests that key mutations are established in early proliferative clones and rapidly causes the majority of tumor growth (5).  

If this is indeed the case, then it will impact quite seriously not only on programs of screening and surveillance, but also on our ideas of the how tumor heterogeneity is generated.

Key publications:

  • The Barrett’s Gland in Phenotype Space.  Cellular and Molecular Gastroenterology and Hepatology, Vol. 1, Issue 1, p41–54
  • Quantification of crypt and stem cell evolution in the normal and neoplastic human colon. Cell Rep; 8:940-7, 2014
  • Lineage tracing reveals multipotent stem cells maintain human adenomas and the pattern of clonal expansion in tumor evolution. Proc Natl Acad Sci U S A;110:E2490-9, 2013
  • Field cancerization in the intestinal epithelium of patients with Crohn's ileocolitis.  Gastroenterology;142:855-864.e8, 2012



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