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Introduction: Colorectal cancer (CRC) is a highly heterogeneous disease, with pathologically similar cancers having completely different responses to treatment and patient survival. Intra-tumour heterogeneity (defined as distinct morphological and phenotypic differences) has recently been demonstrated to be an important factor in the development and behaviour of cancer cells and can be used to determine response to anticancer therapy. Method: Patients with resected CRC had DNA extracted from eight defined tumour areas which were analysed for two genetic mutations (BRAF and KRAS) and one epigenetic trait (CpG island methylator phenotype/CIMP). Normal adjacent tissue was studied as control. Results: Twelve patients with CRC were included. Intra-tumoural heterogeneity for KRAS mutation was seen in 2 patients (17%). There was no statistical evidence of CIMP status heterogeneity ( p = 0.85), but 6 of the 12 patients (50%) demonstrated at least one heterogeneous area within the tumour. Discussion: Intra-tumoural heterogeneity for both genetic and epigenetic factors in CRC is more prevalent than previously thought in Stage II and Stage III CRC. This study provides new insight into epigenetic heterogeneity of CRC and supports the development of a more targeted biopsy strategy to support expansion of personalised treatment. [ABSTRACT FROM AUTHOR]

Few would dispute the efficacy of multimedia technology and the world wide web in promoting declarative knowledge or the acquisition of facts. It is the argument of this paper however that, apart from assisting a learner in "knowing that", these technologies are underestimated in their capacity to facilitate intellectual skills--procedural knowledge or "knowing how". Via examples from children employing information handling skills with a CD-ROM, this paper attempts to illustrate the ways in which new technologies support and enhance a range of skills associated with deep level processing and meaningful learning such as metacognition, problem solving and critical thinking. [ABSTRACT FROM AUTHOR]