Presented by the Kirsten ras in-colorectal-cancer collaborative group

British Journal of Cancer (2001) 85, 692–696. doi:10.1054/bjoc.2001.1964 www.bjcancer.com
Published online 28 August 2001

Kirsten ras mutations in patients with colorectal cancer: the 'RASCAL II' study

H J N Andreyev1,2, A R Norman2, D Cunningham2, J Oates2, B R Dix3, B J Iacopetta3, J Young4, T Walsh5, R Ward6, N Hawkins7, M Beranek8, P Jandik8, R Benamouzig9, E Jullian10, P Laurent-Puig11, S Olschwang11, O Muller12, I Hoffmann12, H M Rabes13, C Zietz13, C Troungos14, C Valavanis15, S T Yuen16, J W C Ho17, C T Croke18, D P O'Donoghue19, W Giaretti20, A Rapallo20, A Russo21, V Bazan21, M Tanaka22, K Omura22, T Azuma23, T Ohkusa24, T Fujimori25, Y Ono25, M Pauly26, C Faber27, R Glaesener28, A F P M de Goeij29, J W Arends29, S N Andersen30, T Lövig30, J Breivik31, G Gaudernack31, O P F Clausen30, P De Angelis30, G I Meling30, T O Rognum30, R Smith32, H-S Goh32, A Font33, R Rosell33, X F Sun34, H Zhang35, J Benhattar36, L Losi36, J Q Lee37, S T Wang38, P A Clarke39, S Bell40, P Quirke40, V J Bubb41, J Piris42, N R Cruickshank43, D Morton43, J C Fox44, F Al-Mulla45, N Lees46, C N Hall46, D Snary47, K Wilkinson48, D Dillon49, J Costa49, V E Pricolo50, S D Finkelstein51, J S Thebo52, A J Senagore52, S A Halter53, S Wadler54, S Malik54, K Krtolica55 and N Urosevic56

  1. 1Department of Medicine & Therapeutics, Imperial College School of Medicine, Chelsea & Westminster Hospital, 369 Fulham Road, London, SW10 9NH, UK
  2. 2Royal Marsden Hospital, Sutton, UK
  3. 3University of Western Australia, Nedlands, Australia
  4. 4Bancroft Centre, Herston, Australia
  5. 5Queensland University of Technology, Australia
  6. 6Department of Medical Oncology, St Vincent's Hospital, Sydney, Australia
  7. 7School of Pathology, University of New South Wales, Sydney, Australia
  8. 8Charles University Hospital, Hradex Kralove, Czech Republic
  9. 9Hospital Avicenne, Bobigny, Paris, France
  10. 10Groupe Hospitalier Cochin-Saint Vincent de Paul, Paris, France
  11. 11>INSERM, Foundation J. Dausset, Paris, France
  12. 12Max-Planck-Institut fur Molekulare Physiologie, Dortmund, Germany
  13. 13Institute of Pathology, Ludwig-Maximilians-University of Munich, Germany
  14. 14Department of Biological Chemistry, University of Athens, Athens, Greece
  15. 15Department of Biology, Morrill Science Centre, University of Massachusetts, USA
  16. 16Department of Pathology, Queen Mary Hospital, Hong Kong
  17. 17Department of Surgery, Queen Mary Hospital, Hong Kong
  18. 18Royal College of Surgeons, Dublin, Eire
  19. 19St Vincent's Hospital, Dublin, Eire
  20. 20Instituto Naziolale per la Ricerca sul Cancro, Genova, Italy
  21. 21Department of Anatomy, surgery & Oncology, Palermo University, Italy
  22. 221st Department of Surgery, School of Medicine, Kanazawa University, Japan
  23. 232nd Department of Internal Medicine, Fukui Medical School, Japan
  24. 241st Department of Internal Medicine, Tokyo Medical & Dental University, Japan
  25. 25Department of Pathology, Dokkyo University School of Medicine, Tochigi, Japan
  26. 26RCMS Lab, Fondation 'Recherche Cancer et Sang', Luxembourg
  27. 27Department of Surgery, St-Theresia-Clinics, Luxembourg
  28. 28Department of Surgery, the Hospital Centre of Luxembourg, Luxembourg
  29. 29Department of Pathology, Masstricht University, The Netherlands
  30. 30The National Hospital, Oslo, Norway
  31. 31The Norwegian Radium Hospital, Oslo, Norway
  32. 32Molecular Biology Laboratory, Tan Tock Seng Hospital, Singapore
  33. 33Medical Oncology Service, Hospital Germans Trias I Pujol, Barcelona, Spain
  34. 34Department of Oncology, University of Linkoping, Sweden
  35. 35Department of Cell Biology, University of Linkoping, Lausanne, Switzerland
  36. 36Institut Universitaire de Pathologie, Lausanne, Switzerland
  37. 37Department of Surgery, National Cheng Kung University, Taiwan
  38. 38Department of Public Health, National Cheng Kung University, Taiwan
  39. 39Institute of Cancer Research, Sutton, UK
  40. 40Molecular Oncology, University of Leeds, UK
  41. 41Department of Pathology, University Medical School, Edinburgh, UK
  42. 42Sir Alastair Currie CRC Laboratories, Edinburgh, UK
  43. 43Queen Elizabeth Hospital, University of Birmingham, UK
  44. 44Zeneca Diagnostics, Northwich, UK
  45. 45Beatson Institute for Cancer Research, Glasgow, UK
  46. 46Department of General Surgery, Wythenshawe Hospital, Manchester, UK
  47. 47Imperial Cancer Research Fund, London
  48. 48St Mark's Hospital, Harrow, UK
  49. 49Yale University School of Medicine, CT, USA
  50. 50Rhode Island Hospital, Brown University, USA
  51. 51Department of Pathology, University of Pittsburgh Medical Centre, MI, USA
  52. 52Ferbuson-Blodget Digestive Disease Institute, Grand Rapids, MI, USA
  53. 53Vanderbilt University, Nashville, TN, USA
  54. 54Albert Einstein College of Medicine, Bronx, NY, USA
  55. 55Institute of Nuclear Sciences 'Vinca', Belgrade, Yugoslavia
  56. 56Military Medical Academy, Belgrade, Yugoslavia

Received 24 January 2001; Revised 14 May 2001; Accepted 15 May 2001.

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Abstract

Researchers worldwide with information about the Kirsten ras (Ki-ras) tumour genotype and outcome of patients with colorectal cancer were invited to provide that data in a schematized format for inclusion in a collaborative database called RASCAL (The Kirsten ras in-colorectal-cancer collaborative group). Our results from 2721 such patients have been presented previously and for the first time in any common cancer, showed conclusively that different gene mutations have different impacts on outcome, even when the mutations occur at the same site on the genome. To explore the effect of Ki-ras mutations at different stages of colorectal cancer, more patients were recruited to the database, which was reanalysed when information on 4268 patients from 42 centres in 21 countries had been entered. After predetermined exclusion criteria were applied, data on 3439 patients were entered into a multivariate analysis. This found that of the 12 possible mutations on codons 12 and 13 of Kirsten ras, only one mutation on codon 12, glycine to valine, found in 8.6% of all patients, had a statistically significant impact on failure-free survival (P = 0.004, HR 1.3) and overall survival (P = 0.008, HR 1.29). This mutation appeared to have a greater impact on outcome in Dukes' C cancers (failure-free survival, P = 0.008, HR 1.5; overall survival P = 0.02, HR 1.45) than in Dukes' B tumours (failure-free survival, P = 0.46, HR 1.12; overall survival P = 0.36, HR 1.15). Ki-ras mutations may occur early in the development of pre-cancerous adenomas in the colon and rectum. However, this collaborative study suggests that not only is the presence of a codon 12 glycine to valine mutation important for cancer progression but also that it may predispose to more aggressive biological behaviour in patients with advanced colorectal cancer. © 2001 Cancer Research Campaign www.bjcancer.com

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References

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