Skip to main content

Advertisement

Log in

An Unusual Combination: KRAS and BRAF Co-mutated Metastatic Colorectal Cancer

  • Case Report
  • Published:
Journal of Gastrointestinal Cancer Aims and scope Submit manuscript

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

References

  1. Phipps AI, Buchanan D, Makar KW, et al. KRAS-mutation status in relation to colorectal cancer survival: the joint impact of correlated tumour markers. Br J Cancer. 2013;108:1757–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Thibodeau SN, Bren G, Schaid D. Microsatellite instability in cancer of the proximal colon. Science. 1993;260:816–9.

    Article  CAS  PubMed  Google Scholar 

  3. Marra G, Boland CR. Hereditary nonpolyposis colorectal cancer: the syndrome, the genes, and historical perspectives. J Natl Cancer Inst. 1995;87:1114–25.

    Article  CAS  PubMed  Google Scholar 

  4. Bronner CE, Baker SM, Morrison PT, et al. Mutation in the DNA mismatch repair gene homologue hMLH1 is associated with hereditary non-polyposis colon cancer. Nature. 1994;368:258–61.

    Article  CAS  PubMed  Google Scholar 

  5. Cunningham JM, Christensen ER, Tester DJ, et al. Hypermethylation of the hMLH1 promoter in colon cancer with microsatellite instability. Cancer Res. 1998;58:3455–60.

    CAS  PubMed  Google Scholar 

  6. Andreyev HJ, Norman AR, Cunningham D, et al. Kirsten ras mutations in patients with colorectal cancer: the multicenter “RASCAL” study. J Natl Cancer Inst. 1998;90:675–84.

    Article  CAS  PubMed  Google Scholar 

  7. De Roock W, Claes B, Bernasconi D, et al. Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis. Lancet Oncol. 2010;11:753–62.

    Article  PubMed  Google Scholar 

  8. De Roock W, Jonker DJ, Di Nicolantonio F, et al. Association of KRAS p.G13D mutation with outcome in patients with chemotherapy-refractory metastatic colorectal cancer treated with cetuximab. JAMA. 2010;304:1812–20.

    Article  PubMed  Google Scholar 

  9. Gnanasampanthan G, Elsaleh H, McCaul K, et al. Ki-ras mutation type and the survival benefit from adjuvant chemotherapy in Dukes’ C colorectal cancer. J Pathol. 2001;195:543–8.

    Article  CAS  PubMed  Google Scholar 

  10. Hutchins G, Southward K, Handley K, et al. Value of mismatch repair, KRAS, and BRAF mutations in predicting recurrence and benefits from chemotherapy in colorectal cancer. J Clin Oncol. 2011;29:1261–70.

    Article  PubMed  Google Scholar 

  11. Imamura Y, Morikawa T, Liao X, et al. Specific mutations in KRAS codons 12 and 13, and patient prognosis in 1075 BRAF-wild-type colorectal cancers. Clin Cancer Res. 2012;18:4753–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Inoue Y, Saigusa S, Iwata T, et al. The prognostic value of KRAS mutations in patients with colorectal cancer. Oncol Rep. 2012;28:1579–84.

    PubMed  Google Scholar 

  13. Lee S, Cho NY, Choi M, et al. Clinicopathological features of CpG island methylator phenotype-positive colorectal cancer and its adverse prognosis in relation to KRAS/BRAF mutation. Pathol Int. 2008;58:104–13.

    Article  CAS  PubMed  Google Scholar 

  14. Roth AD, Tejpar S, Delorenzi M, et al. Prognostic role of KRAS and BRAF in stage II and III resected colon cancer: results of the translational study on the PETACC-3, EORTC 40993, SAKK 60-00 trial. J Clin Oncol. 2010;28:466–74.

    Article  CAS  PubMed  Google Scholar 

  15. Samowitz WS, Curtin K, Schaffer D, et al. Relationship of Ki-ras mutations in colon cancers to tumour location, stage, and survival: a population-based study. Cancer Epidemiol Biomar. 2000;9:1193–7.

    CAS  Google Scholar 

  16. Wang C, van Rijnsoever M, Grieu F, et al. Prognostic significance of microsatellite instability and Ki-ras mutation type in stage II colorectal cancer. Oncology. 2003;64:259–65.

    Article  CAS  PubMed  Google Scholar 

  17. Jass JR. Classification of colorectal cancer based on correlation of clinical, morphological and molecular features. Histopathology. 2007;50:113–30.

    Article  CAS  PubMed  Google Scholar 

  18. Benvenuti S, Sartore-Bianchi A, Di Nicolantonio F, et al. Oncogenic activation of the RAS/RAF signaling pathway impairs the response of metastatic colorectal cancers to anti-epidermal growth factor receptor antibody therapies. Cancer Res. 2007;67:2643–8.

    Article  CAS  PubMed  Google Scholar 

  19. Di Nicolantonio F, Martini M, Molinari F, et al. Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer. J Clin Oncol. 2008;26:5705–12.

    Article  PubMed  Google Scholar 

  20. Souglakos J, Philips J, Wang R, et al. Prognostic and predictive value of common mutations for treatment response and survival in patients with metastatic colorectal cancer. Br J Cancer. 2009;101:465–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Takai Y, Sasaki T, Matozaki T. Small GTP-binding proteins. Physiol Rev. 2001;81:153–208.

    CAS  PubMed  Google Scholar 

  22. Giehl K. Oncogenic Ras in tumour progression and metastasis. Biol Chem. 2005;386(193–205):10.

    Google Scholar 

  23. Barbacid M. Ras genes. Annu Rev Biochem. 1987;56:779–827.

    Article  CAS  PubMed  Google Scholar 

  24. Malumbres M, Barbacid M. RAS oncogenes: the first 30 years. Nat Rev Cancer. 2003;3(459–465):17.

    Google Scholar 

  25. Karnoub AE, Weinberg RA. Ras oncogenes: split personalities. Nat Rev Mol Cell Biol. 2008;9:517–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Al-Mulla F, Milner-White EJ, et al. Structural differences between valine-12 and aspartate-12 Ras proteins may modify carcinoma aggression. J Pathol. 1999;187:433–8.

    Article  CAS  PubMed  Google Scholar 

  27. Ogino S, Nosho K, Kirkner GJ, et al. CpG island methylator phenotype, microsatellite instability, BRAF mutation and clinical outcome in colon cancer. Gut. 2009;58:90–6.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Rajagopalan H, Bardelli A, Lengauer C, et al. Tumorigenesis: RAF/RAS oncogenes and mismatch-repair status. Nature. 2002;418:934.

    Article  CAS  PubMed  Google Scholar 

  29. Frattini M, Balestra D, Suardi S, et al. Different genetic features associated with colon and rectal carcinogenesis. Clin Cancer Res. 2004;10:4015–21.

    Article  CAS  PubMed  Google Scholar 

  30. Ahlquist T, Bottillo I, Danielsen SA, et al. RAS signaling in colorectal carcinomas through alteration of RAS, RAF, NF1, and/or RASSF1A. Neoplasia. 2008;10:680–6.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Cerami E, Gao J, Dogrusoz U, et al. The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov. 2012;2:401–4.

    Article  PubMed  Google Scholar 

  32. Bokemeyer C, Cutsem EV, Rougier P, et al. Addition of cetuximab to chemotherapy as first-line treatment for KRAS wild-type metastatic colorectal cancer: pooled analysis of the CRYSTAL and OPUS randomised clinical trials. Eur J Cancer. 2012;48:1466–75.

    Article  CAS  PubMed  Google Scholar 

  33. Lin AY, Buckley NS, Lu AT, et al. Effect of KRAS mutational status in advanced colorectal cancer on the outcomes of anti-epidermal growth factor receptor monoclonal antibody therapy: a systematic review and meta-analysis. Clin Colorectal Cancer. 2011;10:63–9.

    Article  CAS  PubMed  Google Scholar 

  34. Van Cutsem E, Kohne CH, Lang I, et al. Cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumor KRAS and BRAF mutation status. J Clin Oncol. 2011;29:2011–9.

    Article  PubMed  Google Scholar 

  35. Douillard JY, Siena S, Cassidy J, et al. Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study. J Clin Oncol. 2010;28:4697–705.

    Article  CAS  PubMed  Google Scholar 

  36. Bokemeyer C, Bondarenko I, Makhson A, et al. Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer. J Clin Oncol. 2009;27:663–71.

    Article  CAS  PubMed  Google Scholar 

  37. De Roock W, De Vriendt V, Normanno N, et al. KRAS, BRAF, PIK3CA, and PTEN mutations: implications for targeted therapies in metastatic colorectal cancer. Lancet Oncol. 2011;12:594–603.

    Article  PubMed  Google Scholar 

  38. Yokota T, Ura T, Shibata N, et al. BRAF mutation is a powerful prognostic factor in advanced and recurrent colorectal cancer. Br J Cancer. 2011;104:856–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Andreyev HJ, Norman AR, Cunningham D, et al. Kirsten ras mutations in patients with colorectal cancer: the ‘RASCAL II’ study. Br J Cancer. 2001;85:692–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Guastadisegni C, Colafranceschi M, Ottini L, et al. Microsatellite instability as a marker of prognosis and response to therapy: a metaanalysis of colorectal cancer survival data. Eur J Cancer. 2010;46:2788–98.

    Article  CAS  PubMed  Google Scholar 

  41. Ogino S, Meyerhardt JA, Irahara N, et al. KRAS mutation in stage III colon cancer and clinical outcome following intergroup trial CALGB 89803. Clin Cancer Res. 2009;15:7322–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Nash GM, Gimbel M, Cohen AM, et al. KRAS mutation and microsatellite instability: two genetic markers of early tumour development that influence the prognosis of colorectal cancer. Ann Surg Oncol. 2010;17:416–24.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

The authors thank the Division of Hematology and Oncology for their support and encouragement to write this case report.

Consent

Written informed consent was obtained from the patient for publication of this case report and any accompanying images.

Conflict of Interests

The authors declare that they have no competing interests.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Narendranath Epperla.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Epperla, N., George, B. An Unusual Combination: KRAS and BRAF Co-mutated Metastatic Colorectal Cancer. J Gastrointest Canc 47, 206–209 (2016). https://doi.org/10.1007/s12029-015-9735-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12029-015-9735-y

Keywords

Navigation