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Positive association of PIK3CA mutation with KRAS mutation but not BRAF mutation in colorectal cancer suggests co-selection is gene specific but not pathway specific
  1. Susanti Susanti1,2,3,
  2. Wakkas Fadhil1,3,
  3. Shamayal Murtaza1,
  4. James C Hassall1,3,
  5. Henry O Ebili1,3,4,
  6. Anca Oniscu5,
  7. Mohammad Ilyas1,3
  1. 1 Molecular Pathology Group, Unit of Academic Molecular Pathology, Division of Cancer and Stem Cell, School of Medicine, University of Nottingham, Queen’s Medical Centre Campus, Nottingham, UK
  2. 2 Deparment of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, University of Muhammadiyah Purwokerto, Central Java, Indonesia
  3. 3 Nottingham Molecular Pathology Node, University of Nottingham, Queen’s Medical Centre Campus, Nottingham, UK
  4. 4 Department of Morbid Anatomy and Histopathology, Olabisi Onabanjo University, Ago-Iwoye, Nigeria
  5. 5 Molecular Pathology, Royal Infirmary of Edinburgh, Edinburgh, UK
  1. Correspondence to Professor Mohammad Ilyas, Division of Pathology, University of Nottingham, Nottingham NG72UH, UK; mohammad.ilyas{at}

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Mutation in KRAS, BRAF and PIK3CA are commonly present in colorectal cancer (CRC). KRAS and BRAF form part of the mitogen-activated protein kinase (MAPK) signalling pathway and KRAS lies immediately upstream of BRAF. Consequently, KRAS and BRAF mutations are mutually exclusive with mutation in either one causing activation of MAPK signalling.1 PIK3CA forms part of the phosphatidylinositide‐3‐kinase PI3K signalling pathway, and several studies have shown a significant association of KRAS and PIK3CA mutation in several cancer types including CRC.1–3 At face value, there would appear to be positive co-selection of MAPK and PI3K signalling activation implying synergy between these two pathways. If this were true, then a similar positive association would be expected between mutation of BRAF and PIK3CA. To date, less consistent or no association of BRAF and PIK3CA mutation has been reported.1 3 4 However, it is well established that BRAF mutation is strongly associated with microsatellite instability (MSI) in CRC. We therefore sought to test the association between mutation of BRAF and PIK3CA …

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  • Handling editor Runjan Chetty.

  • Contributors SS, WF, MI: conception or design of the work. SS, WF, SM, JCH, HOE: data collection. SS, WF, SM: data analysis and interpretation. SS, MI: drafting the article. AO, MI: critical revision of the article. All: final approval of the version to be published.

  • Funding This study was funded by EC Marie Curie Actions, AIDPATH project (Contract No. 612471) and Nottingham Molecular Pathology Node (NMPN) MR/N005953/1.

  • Competing interests None declared.

  • Patient consent Not required.

  • Ethics approval Nottingham Health Sciences Biobank which has approval as an IRB from North West—Greater Manchester Central Research Ethics Committee REC reference: 15/NW/0685 and Tissue Governance NHS Lothian under ethics approval number SR783.

  • Provenance and peer review Not commissioned; externally peer reviewed.