Tumor heterogeneity revealed by KRAS, BRAF, and PIK3CA pyrosequencing: KRAS and PIK3CA intratumor mutation profile differences and their therapeutic implications

Human Mutation

Volumn 35, Issue 3, 2014, Pages 329-340

  Kosmidou, Vivian ^a   Oikonomou, Eftychia ^a   Vlassi, Margarita ^a   Avlonitis, Spyros ^b   Katseli, Anastasia ^b   Tsipras, Iraklis ^b   Mourtzoukou, Despina ^b   Kontogeorgos, Georgios ^b   Zografos, Georgios ^b   Pintzas, Alexander ^a  

^a INSTITUTE OF BIOLOGY   (Greece)

^b G GENNIMATAS GENERAL HOSPITAL   (Greece)

Author keywords

BRAF; Colorectal cancer; KRAS; PIK3CA; Tumor heterogeneity

Indexed keywords

ARTICLE; CANCER DIAGNOSIS; CANCER PATIENT; CANCER STAGING; CODON; COLORECTAL CANCER; FEMALE; GENE FREQUENCY; GENE MUTATION; HUMAN; MAJOR CLINICAL STUDY; MALE; NUCLEOTIDE SEQUENCE; ONCOGENE K RAS; PERSONALIZED MEDICINE; POINT MUTATION; PRIORITY JOURNAL; PYROSEQUENCING; TUMOR CLASSIFICATION; TUMOR DIFFERENTIATION;

BRAF; COLORECTAL CANCER; KRAS; PIK3CA; TUMOR HETEROGENEITY;

CODON; COLORECTAL NEOPLASMS; DNA MUTATIONAL ANALYSIS; FEMALE; HUMANS; MALE; PHOSPHATIDYLINOSITOL 3-KINASES; POINT MUTATION; PROTO-ONCOGENE PROTEINS; PROTO-ONCOGENE PROTEINS B-RAF; RAS PROTEINS;

EID: 84893962650     PISSN: 10597794     EISSN: 10981004     Source Type: Journal    
DOI: 10.1002/humu.22496     Document Type: Article

References (68)

1. Abubaker J, Bavi P, Al-Harbi S, Ibrahim M, Siraj AK, Al-Sanea N, Abduljabbar A, Ashari LH, Alhomoud S, Al-Dayel F, Uddin S, Al-Kuraya KS. 2008. Clinicopathological analysis of colorectal cancers with PIK3CA mutations in Middle Eastern population. Oncogene 27:3539-3545.
2. Amado RG, Wolf M, Peeters M, Van Cutsem E, Siena S, Freeman DJ, Juan T, Sikorski R, Suggs S, Radinsky R, Patterson SD, Chang DD. 2008. Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol 26:1626-1634.
3. Bagadi SB, Sanghvi M, Nair SB, Das BR. 2012. Combined mutational analysis of KRAS, NRAS and BRAF genes in Indian patients with colorectal carcinoma. Int J Biol Markers 27:27-33.
4. Baldus S, Schaefer K, Engers R, Hartleb D, Stoecklein N, Gabbert H. 2010. Prevalence and heterogeneity of KRAS, BRAF, and PIK3CA mutations in primary colorectal adenocarcinomas and their corresponding metastases. Clin Cancer Res 16:790-799.
5. Barault L, Veyrie N, Jooste V, Lecorre D, Chapusot C, Ferraz JM, Lièvre A, Cortet M, Bouvier AM, Rat P, Roignot P, Faivre J, et al. 2008. Mutations in the RAS-MAPK, PI(3)K signalling network correlate with poor survival in a population-based series of colon cancers. Int J Cancer 122:2255-2259.
6. Benvenuti S, Sartore-Bianchi A, Di Nicolantonio F, Zanon C, Moroni M, Veronese S, Siena S, Bardelli A. 2007. Oncogenic activation of the RAS/RAF signalling pathway impairs the response of metastatic colorectal cancers to anti-epidermal growth factor receptor antibody therapies. Cancer Res 67:2643-2648.
7. Benvenuti S, Frattini M, Arena S, Zanon C, Cappelletti V, Coradini D, Daidone MG, Pilotti S, Pierotti MA, Bardelli A. 2008. PIK3CA cancer mutations display gender and tissue specificity patterns. Hum Mutat 29:284-288.
8. Bibeau F, Frugier H, Crapez E, Lamy P, Ychou M, Boissière-Michot F. 2010. KRAS mutation testing in patients with metastatic colorectal carcinoma: an 18-month experience emphasizing the risk of false-negative results. J Clin Oncol 28:3572.
9. Bishehsari F, Mahdavinia M, Malekzadeh R, Verginelli F, Catalano T, Sotoudeh M, Bazan V, Agnese V, Esposito DL, De Lellis L, Semeraro D, Colucci G, et al. 2006. Patterns of K-ras mutation in colorectal carcinomas from Iran and Italy: influence of microsatellite instability status and country of origin. Ann Oncol 17:791-796.
10. Bos JL. 1989. Ras oncogenes in human cancer: a review. Cancer Res 49:4682-4689.
11. Calistri D, Rengucci C, Seymour I, Lattuneddu A, Polifemo AM, Monti F, Saragoni L, Amadori D. 2005. Mutation analysis of p53, K-ras and BRAF genes in colorectal cancer progression. J Cell Physiol 204:484-488.
12. Carotenuto P, Roma C, Rachiglio AM, Tatangelo F, Pinto C, Ciardiello F, Nappi O, Iaffaioli V, Botti G, Normanno N. 2010. Detection of KRAS mutations in colorectal carcinoma patients with an integrated PCR/sequencing and real-time PCR approach. Pharmacogenomics 11:1169-1179.
13. Chen C-C, Er T-K, Liu Y-Y, Hwang J-K, Barrio MJ. 2013. Computational Analysis of KRAS mutations: implications for different effects on the KRAS p.G12D and p.G13D mutations. PLoS ONE 8:e55793.
14. Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, Teague J, Woffendin H, Garnett MJ, Bottomley W, Davis N, Dicks E, et al. 2002. Mutations of the BRAF gene in human cancer. Nature 417:949-954.
15. de Castro-Carpeño J, Belda-Iniesta C, Casado Sáenz E, Hernández Agudo E, Feliu Battle J, González Barón M. 2008. EGFR and colon cancer: a clinical view. Clin Transl Oncol 10:6-13.
16. De Roock W, Jonker DJ, Di Nicolantonio F, Sartore-Bianchi A, Tu D. 2010. Association of KRAS p.G13D mutation with outcome in patients with chemotherapy-refractory metastatic colorectal cancer treated with cetuximab. JAMA 304:1812-1820.
17. De Roock W, De Vriendt V, Normanno N, Ciardiello F, Tejpar S. 2011. KRAS, BRAF, PIK3CA, and PTEN mutations: implications for targeted therapies in metastatic colorectal cancer. Lancet Oncol 12:594-603.
18. Deschoolmeester V, Baay M, Specenier P, Lardon F, Vermorken J. 2010. A review of the most promising biomarkers in colorectal cancer: one step closer to targeted therapy. Oncologist 15:699-731.
19. Diaz LA Jr, Williams RT, Wu J, Kinde I, Hecht JR, Berlin J, Allen B, Bozic I, Reiter JG, Nowak MA, Kinzler KW, Oliner KS, et al. 2012. The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers. Nature 486:537-540.
20. Edkins S, O'Meara S, Parker A, Stevens C, Reis M, Jones S, Greenman C, Davies H, Dalgliesh G, Forbes S, Hunter C, Smith R, et al. 2006. Recurrent KRAS codon 146 mutations in human colorectal cancer. Cancer Biol Ther 5:928-932.
21. Eklöf V, Wikberg ML, Edin S, Dahlin AM, Jonsson B-A, Öberg Å, Rutegård J, Palmqvist R. 2013. The prognostic role of KRAS, BRAF, PIK3CA and PTEN in colorectal cancer. Br J Cancer 108:2153-2163.
22. Engelman JA. 2009. Targeting PI3K signalling in cancer: opportunities, challenges and limitations. Nat Rev Cancer 9:550-562.
23. Fariña-Sarasqueta A, van Lijnschoten G, Moerland E, Creemers GJ, Lemmens VE, Rutten HJ, van den Brule AJ. 2010. The BRAF V600E mutation is an independent prognostic factor for survival in stage II and stage III colon cancer patients. Ann Oncol 21:2396-2402.
24. Fearon ER, Vogelstein B. 1990. A genetic model for colorectal tumourigenesis. Cell 61:759-767.
25. Ferte C, Andre F, Soria J. 2010. Molecular circuits of solid tumours: prognostic and predictive tools for bedside use. Nat Rev Clin Oncol 7:367-380.
26. Fransen K, Klintenäs M, Osterström A, Dimberg J, Monstein HJ, Söderkvist P. 2004. Mutation analysis of the BRAF, ARAF and RAF-1 genes in human colorectal adenocarcinomas. Carcinogenesis 25:527-533.
27. Gerlinger M, Rowan AJ, Horswell S, Larkin J, Endesfelder D, Gronroos E Martinez P, Matthews N, Stewart A, Tarpey P, Varela I, Phillimore B, et al. 2012. Intratumour heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med 366:883-892.
28. Imamura Y, Morikawa T, Liao X, Lochhead P, Kuchiba A, Yamauchi M, Qian ZR, Nishihara R, Meyerhardt JA, Haigis KM, Fuchs CS, Ogino S. 2012. Specific mutations in KRAS codons 12 and 13 and patient prognosis in 1075 BRAF wild-type colorectal cancers. Clin Cancer Res 18:4753-4763.
29. Kang S, Bader AG, Vogt PK. 2005. Phosphatidylinositol 3-kinase mutations identified in human cancer are oncogenic. Proc Natl Acad Sci USA 102:802-807.
30. Karapetis CS, Khambata-Ford S, Jonker DJ, O'Callaghan CJ, Tu D, Tebbutt NC, Simes RJ, Chalchal H, Shapiro JD, Robitaille S, Price TJ, Shepherd L, et al. 2008. K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med 359:1757-1765.
31. Kato S, Iida S, Higuchi T, Ishikawa T, Takagi Y, Yasuno M, Enomoto M, Uetake H, Sugihara K. 2007. PIK3CA mutation is predictive of poor survival in patients with colorectal cancer. Int J Cancer 121:1771-1778.
32. Kim DW, Huamani J, Fu A, Hallahan DE. 2006. Molecular strategies targeting the host component of cancer to enhance tumour response to radiation therapy. Int J Radiat Oncol Biol Phys 64:38-46.
33. Kobunai T, Watanabe T, Yamamoto Y, Eshima K. 2010. The frequency of KRAS mutation detection in human colon carcinoma is influenced by the sensitivity of assay methodology: a comparison between direct sequencing and real-time PCR. Biochem Biophys Res Commun 395:158-162.
34. Lee A, Swanton C. 2012. Tumour heterogeneity and drug resistance: personalising cancer medicine through functional genomics. Biochem Pharmacol 83:1013-1020.
35. Li HT, Lu YY, An YX, Wang X, Zhao QC. 2011. KRAS, BRAF and PIK3CA mutations in human colorectal cancer: relationship with metastatic colorectal cancer. Oncol Rep 25:1691-1697.
36. Liao X, Lochhead P, Nishihara R, Morikawa T, Kuchiba A, Yamauchi M, Imamura Y, Qian ZR, Baba Y, Shima K, Sun R, Nosho K, et al. 2012. Aspirin use, tumour PIK3CA mutation, and colorectal-cancer survival. N Engl J Med 367:1596-1606.
37. Loupakis F, Ruzzo A, Cremolini C, Vincenzi B, Salvatore L, Santini D, Masi G, Stasi I, Canestrari E, Rulli E, Floriani I, Bencardino K, et al. 2009. KRAS codon 61, 146 and BRAF mutations predict resistance to cetuximab plus irinotecan in KRAS codon 12 and 13 wild-type metastatic colorectal cancer. Br J Cancer 101:715-721.
38. Mancini I, Santucci C, Sestini R, Simi L, Pratesi N, Cianchi F, Valanzano R, Pinzani P, Orlando C. 2010. The use of COLD-PCR and high-resolution melting analysis improves the limit of detection of KRAS and BRAF mutations in colorectal cancer. J Mol Diagn 12:705-711.
39. Mancuso A, Sollami R, Recine F, Cerbone L, Macciomei MC, Leone A. 2010. Patient with colorectal cancer with heterogeneous KRAS molecular status responding to cetuximab-based chemotherapy. J Clin Oncol 28:e756-e758.
40. McCubrey JA, Steelman LS, Abrams SL, Lee JT, Chang F, Bertrand FE, Navolanic PM, Terrian DM, Franklin RA, D'Assoro AB, Salisbury JL, Mazzarino MC, et al. 2006. Roles of the RAF/MEK/ERK and PI3K/PTEN/AKT pathways in malignant transformation and drug resistance. Adv Enzyme Regul 46:249-279.
41. Messner I, Cadeddu G, Huckenbeck W, Knowles HJ, Gabbert HE 2013. KRAS p.G13D mutations are associated with sensitivity to anti-EGFR antibody treatment in colorectal cancer cell lines. J Cancer Res Clin Oncol 139:201-209.
42. Misale S, Yaeger R, Hobor S, Scala E, Janakiraman M, Liska D, Valtorta E, Schiavo R, Buscarino M, Siravegna G, Bencardino K, Cercek A, et al. 2012. Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer. Nature 486:532-536.
43. Molinari F, Felicioni L, Buscarino M, De Dosso S, Buttitta F, Malatesta S, Movilia A, Luoni M, Boldorini R, Alabiso O, Girlando S, Soini B, et al. 2011. Increased detection sensitivity for KRAS mutations enhances the prediction of anti-EGFR monoclonal antibody resistance in metastatic colorectal cancer. Clin Cancer Res 14:4901-4914.
44. Nishihara R, Lochhead P, Kuchiba A, Jung S, Yamauchi M, Liao X, Imamura Y, Rong Qian Z, Morikawa T, Wang M, Spiegelman D, Cho E, et al. 2013. Aspirin use and risk of colorectal cancer according to BRAF mutation status. JAMA 309:2563-2571.
45. Ogino S, Kawasaki T, Brahmandam M, Yan L, Cantor M, Namgyal C, Mino-Kenudson M, Lauwers GY, Loda M, Fuchs CS. 2005. Sensitive sequencing method for KRAS mutation detection by pyrosequencing. J Mol Diagn 7:413-421.
46. Ogino S, Nosho K, Kirkner GJ, Shima K, Irahara N, Kure S, Chan AT, Engelman JA, Kraft P, Cantley LC, Giovannucci EL, Fuchs CS. 2009. PIK3CA mutation is associated with poor prognosis among patients with curatively resected colon cancer. J Clin Oncol 27:1477-1484.
47. Ollikainen M, Gylling A, Puputti M, Nupponen NN, Abdel-Rahman WM, Butzow R, Peltomäki P. 2007. Patterns of PIK3CA alterations in familial colorectal and endometrial carcinoma. Int J Cancer 121:915-920.
48. Oltedal S, Aasprong O, Moller J, Korner H, Gilje B, Tjensvoll K, Birkemeyer EM, Heikkila R, Smaaland R, Nordgard O. 2011. Heterogeneous distribution of K-ras mutations in primary colon carcinomas: implications for EGFR-directed therapy. Int J Colorectal Dis 26:1271-1277.
49. Parsons BL. 2008. Many different tumour types have polyclonal tumour origin: evidence and implications. Mutat Res 659:232-247.
50. Prenen H, De Schutter J, Jacobs B, De Roock W, Biesmans B, Claes B, Lambrechts D, Van Cutsem E, Tejpar S. 2009. PIK3CA mutations are not a major determinant of resistance to the epidermal growth factor receptor inhibitor cetuximab in metastatic colorectal cancer. Clin Cancer Res 15:3184-3188.
51. Qiu W, Tong GX, Manolidis S, Close LG, Assaad AM, Su GH. 2008. Novel mutant-enriched sequencing identified high frequency of PIK3CA mutations in pharyngeal cancer. Int J Cancer 122:1189-1194.
52. Richman SD, Chambers P, Seymour MT, Daly C, Grant S, Hemmings G, Quirke P. 2011. Intratumoral heterogeneity of KRAS and BRAF mutation status in patients with advanced colorectal cancer (aCRC) and cost-effectiveness of multiple sample testing. Anal Cell Path 34:61-66.
53. Rogers SJ, Box C, Harrington KJ, Nutting C, Rhys-Evans P, Eccles SA. 2005. The phosphatidylinositol 3-kinase signalling pathway as a therapeutic target in squamous cell carcinoma of the head and neck. Expert Opin Ther Targets 9:769-790.
54. Samowitz WS, Sweeney C, Herrick J, Albertsen H, Levin TR, Murtaugh MA, Wolff RK, Slattery ML. 2005. Poor survival associated with the BRAF V600E mutation in microsatellite-stable colon cancers. Cancer Res 65:6063-6069.
55. Samuels Y, Wang Z, Bardelli A, Silliman N, Ptak J, Szabo S, Yan H, Gazdar A, Powell SM, Riggins GJ, Willson JK, Markowitz S, et al. 2004. High frequency of mutations of the PIK3CA gene in human cancers. Science 304:554.
56. Samuels Y, Velculescu VE. 2004. Oncogenic mutations of PIK3CA in human cancers. Cell Cycle 3:1221-1224.
57. Scaltriti M, Baselga J. 2006. The epidermal growth factor receptor pathway: a model for targeted therapy. Clin Cancer Res 12:5268-5272.
58. Shao RX, Kato N, Lin LJ, Muroyama R, Moriyama M, Ikenoue T, Watabe H, Otsuka M, Guleng B, Ohta M, Tanaka Y, Kondo S, et al. 2006. Absence of tyrosine kinase mutations in Japanese colorectal cancer patients. Oncogene 26:2133-2135.
59. Shayesteh L, Lu Y, Kuo WL, Baldocchi R, Godfrey T, Collins C, Pinkel D, Powell B, Mills GB, Gray JW. 1999. PIK3CA is implicated as an oncogene in ovarian cancer. Nat Genet 21:99-102.
60. Souglakos J, Philips J, Wang R, Marwah S, Silver M, Tzardi M, Silver J, Ogino S, Hooshmand S, Kwak E, Freed E, Meyerhardt JA, et al. 2009. Prognostic and predictive value of common mutations for treatment response and survival in patients with metastatic colorectal cancer. Br J Cancer 101:465-472.
61. Swanton C. 2012. Intratumour heterogeneity: evolution through space and time. Cancer Res 72:4875-4882.
62. Thirlwell C, Will OC, Domingo E, Graham TA, McDonald SA, Oukrif D, Jeffrey R, Gorman M, Rodriguez-Justo M, Chin-Aleong J, Clark SK, Novelli MR, et al. 2010. Clonality assessment and clonal ordering of individual neoplastic crypts shows polyclonality of colorectal adenomas. Gastroenterology 138:1441-1454.
63. Tsiatis AC, Norris-Kirby A, Rich RG, Hafez MJ, Gocke CD, Eshleman JR, Murphy KM. 2010. Comparison of Sanger sequencing, pyrosequencing, and melting curve analysis for the detection of KRAS mutations: diagnostic and clinical implications. J Mol Diagn 12:425-432.
64. Velho S, Oliveira C, Ferreira A, Ferreira AC, Suriano G, Schwartz S Jr, Duval A, Carneiro F, Machado JC, Hamelin R, Seruca R. 2005. The prevalence of PIK3CA mutations in gastric and colon cancer. Eur J Cancer 41:1649-1654.
65. Wu C-M, Tang R, Wang JY, Changchien CR, Hsieh LL. 2004. Frequency and spectrum of K-RAS codons 12 and 13 mutations in colorectal adenocarcinomas from Taiwan. Cancer Genet Cytogenet 158:55-60.
66. Yeo MK, Liang ZL, Oh T, Moon Y, An S, Kim MK, Kim KS, Shong M, Kim JM, Jo YS. 2011. Pyrosequencing cut-off value identifying BRAFV600E mutation in fine needle aspiration samples of thyroid nodules. Clin Endocrinol (Oxf) 75:555-560.
67. Zeki SS, Graham TA, Wright NA. 2011. Stem cells and their implications for colorectal cancer. Nat Rev Gastroenterol Hepatol 8:90-100.
68. Zlobec I, Lugli A. 2008. Prognostic and predictive factors in colorectal cancer. J Clin Pathol 61:561-569.