title: Genetic and Epigenetic Intra-tumour Heterogeneity in Colorectal Cancer.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Colorectal Surgery, Singleton Hospital, Abertawe Bro Morgannwg University Local Health Board, Sketty Lane, Swansea, SA2 8QA, UK. huwgjones@hotmail.com.|, 16 Forrest Road, Canton, Cardiff, CF5 1HR, UK. huwgjones@hotmail.com.
authors.forename: Huw Geraint
authors.identifier: 0000-0003-0365-9049
authors.initials: HG
authors.lastname: Jones
authors.affiliation: Institute of Life Science, Singleton Park, Swansea University, Swansea, SA2 8PP, UK.
authors.forename: Gareth
authors.initials: G
authors.lastname: Jenkins
authors.affiliation: Department of Pathology, Singleton Hospital, Abertawe Bro Morgannwg University Local Health Board, Sketty Lane, Swansea, SA2 8QA, UK.
authors.forename: Namor
authors.initials: N
authors.lastname: Williams
authors.affiliation: Department of Pathology, Singleton Hospital, Abertawe Bro Morgannwg University Local Health Board, Sketty Lane, Swansea, SA2 8QA, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Griffiths
authors.affiliation: Leeds Institute of Cancer and Pathology, Wellcome Trust Brenner Building, Level 4, St. James's University Hospital, Leeds, LS9 7TF, UK.
authors.forename: Phil
authors.initials: P
authors.lastname: Chambers
authors.affiliation: Department of Colorectal Surgery, Singleton Hospital, Abertawe Bro Morgannwg University Local Health Board, Sketty Lane, Swansea, SA2 8QA, UK.
authors.forename: John
authors.initials: J
authors.lastname: Beynon
authors.affiliation: Department of Colorectal Surgery, Singleton Hospital, Abertawe Bro Morgannwg University Local Health Board, Sketty Lane, Swansea, SA2 8QA, UK.
authors.forename: Dean
authors.initials: D
authors.lastname: Harris
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D018899:CpG Islands / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*
chemical_list: D004273:DNA, Neoplasm; C117307:KRAS protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras)