• 1
    Cunningham D, Humblet Y, Siena S, et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 2004;351:33745.
  • 2
    Van Cutsem E, Peeters M, Siena S, et al. Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. J Clin Oncol 2007;25:165864.
  • 3
    Jonker DJ, O'Callaghan CJ, Karapetis CS, et al. Cetuximab for the treatment of colorectal cancer. N Engl J Med 2007;357:20408.
  • 4
    Barault L, Veyrie N, Jooste V, et al. Mutations in the RAS-MAPK, PI(3)K (phosphatidylinositol-3-OH kinase) signaling network correlate with poor survival in a population-based series of colon cancers. Int J Cancer 2008;122:22559.
  • 5
    Lievre A, Bachet JB, Le Corre D, et al. KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer. Cancer Res 2006;66:39925.
  • 6
    Loupakis F, Pollina L, Stasi I, et al. PTEN expression and KRAS mutations on primary tumors and metastases in the prediction of benefit from cetuximab plus irinotecan for patients with metastatic colorectal cancer. J Clin Oncol 2009;27:26229.
  • 7
    Khambata-Ford S, Garrett CR, Meropol NJ, et al. Expression of epiregulin and amphiregulin and K-ras mutation status predict disease control in metastatic colorectal cancer patients treated with cetuximab. J Clin Oncol 2007;25:32307.
  • 8
    Amado RG, Wolf M, Peeters M, et al. Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol 2008;26:162634.
  • 9
    Karapetis CS, Khambata-Ford S, Jonker DJ, et al. K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med 2008;359:175765.
  • 10
    Lievre A, Bachet JB, Boige V, et al. KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab. J Clin Oncol 2008;26:3749.
  • 11
    European Medicines Agency. Committee for Medicinal Products for Human Use post-authorisation summary of positive opinion for Erbitux. Available at:
  • 12
    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;26:570512.
  • 13
    Loupakis F, Ruzzo A, Cremolini C, et al. 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 2009;101:71521.
  • 14
    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;29:20119.
  • 15
    Chapman PB, Hauschild A, Robert C, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med 2011;364:250716.
  • 16
    Artale S, Sartore-Bianchi A, Veronese SM, et al. Mutations of KRAS and BRAF in primary and matched metastatic sites of colorectal cancer. J Clin Oncol 2008;26:42179.
  • 17
    Tie J, Lipton L, Desai J, et al. KRAS mutation is associated with lung metastasis in patients with curatively resected colorectal cancer. Clin Cancer Res 2011;17:112230.
  • 18
    Sastre J, Maestro ML, Puente J, Veganzones S, Alfonso R, Rafael S, Garcia-Saenz JA, Vidaurreta M, Martin M, Arroyo M, et al. Circulating tumor cells in colorectal cancer: correlation with clinical and pathological variables. Ann Oncol 2008;19:9358.
  • 19
    Gervasoni A, Monasterio Munoz RM, Wengler GS, et al. Molecular signature detection of circulating tumor cells using a panel of selected genes. Cancer Lett 2008;263:26779.
  • 20
    Sieuwerts AM, Kraan J, Bolt-de Vries J, et al. Molecular characterization of circulating tumor cells in large quantities of contaminating leukocytes by a multiplex real-time PCR. Breast Cancer Res Treat 2009;118:45568.
  • 21
    Morlan J, Baker J, Sinicropi D. Mutation detection by real-time PCR: a simple, robust and highly selective method. PLoS One 2009;4:e4584.
  • 22
    Keller JW, Haigis KM, Franklin JL, et al. Oncogenic K-RAS subverts the antiapoptotic role of N-RAS and alters modulation of the N-RAS:gelsolin complex. Oncogene 2007;26:30519.
  • 23
    Hollestelle A, Nagel JH, Smid M, et al. Distinct gene mutation profiles among luminal-type and basal-type breast cancer cell lines. Breast Cancer Res Treat 2010;121:5364.
  • 24
    Lalmahomed ZS, Kraan J, Gratama JW, et al. Circulating tumor cells and sample size: the more, the better. J Clin Oncol 2010;28:e2889; author reply e90.
  • 25
    Gross S, Bui T, Rao C, et al. Modified Ficoll preprocessing procedure for 30 mL of whole blood prior to CellSearch circulating tumor cell test. Presented at the 5th International Symposium on Minimal Residual Cancer, San Francisco, California, 2005.
  • 26
    Sieuwerts AM, Mostert B, Bolt-de Vries J, et al. mRNA and microRNA expression profiles in circulating tumor cells and primary tumors of metastatic breast cancer patients. Clin Cancer Res 2011;17:360018.
  • 27
    Sieuwerts AM, Meijer-van Gelder ME, Timmermans M, et al. How ADAM–9 and ADAM-11 differentially from estrogen receptor predict response to tamoxifen treatment in patients with recurrent breast cancer: a retrospective study. Clin Cancer Res 2005;11:731121.
  • 28
    Hsieh SM, Look MP, Sieuwerts AM, et al. Distinct inherited metastasis susceptibility exists for different breast cancer subtypes: a prognosis study. Breast Cancer Res 2009;11:R75.
  • 29
    Adam R, de Haas RJ, Wicherts DA, et al. Is hepatic resection justified after chemotherapy in patients with colorectal liver metastases and lymph node involvement? J Clin Oncol 2008;26:367280.
  • 30
    Zuo Z, Chen SS, Chandra PK, et al. Application of COLD-PCR for improved detection of KRAS mutations in clinical samples. Mod Pathol 2009;22:102331.
  • 31
    Li J, Wang L, Mamon H, et al. Replacing PCR with COLD-PCR enriches variant DNA sequences and redefines the sensitivity of genetic testing. Nat Med 2008;14:57984.
  • 32
    Hancer VS, Buyukdogan M, Turkmen I, et al. Comparison of KRAS mutation tests in colorectal cancer patients. Genet Test Mol Biomarkers 2011;15:8314.
  • 33
    Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci USA 1977;74:54637.
  • 34
    Catalogue of Somatic Mutations in Cancer, Wellcome Trust Sanger Institute. Available at:
  • 35
    Baldus SE, Schaefer KL, Engers R, et al. Prevalence and heterogeneity of KRAS, BRAF, and PIK3CA mutations in primary colorectal adenocarcinomas and their corresponding metastases. Clin Cancer Res 2010;16:7909.
  • 36
    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;11:75362.
  • 37
    Milbury CA, Chen CC, Mamon H, et al. Multiplex amplification coupled with COLD-PCR and high resolution melting enables identification of low-abundance mutations in cancer samples with low DNA content. J Mol Diagn 2011;13:22032.
  • 38
    Jiang Y, Palma JF, Agus DB, et al. Detection of androgen receptor mutations in circulating tumor cells in castration-resistant prostate cancer. Clin Chem 2010;56:14925.
  • 39
    Maheswaran S, Sequist LV, Nagrath S, et al. Detection of mutations in EGFR in circulating lung-cancer cells. N Engl J Med 2008;359:36677.
  • 40
    Papavasiliou P, Fisher T, Kuhn J, et al. Circulating tumor cells in patients undergoing surgery for hepatic metastases from colorectal cancer. Proc (Bayl Univ Med Cent) 2010;23:114.
  • 41
    Allan AL, Keeney M. Circulating tumor cell analysis: technical and statistical considerations for application to the clinic. J Oncol 2010;2010:426218.
  • 42
    Campbell PJ, Yachida S, Mudie LJ, et al. The patterns and dynamics of genomic instability in metastatic pancreatic cancer. Nature 2010;467:110913.
  • 43
    Santini D, Loupakis F, Vincenzi B, et al. High concordance of KRAS status between primary colorectal tumors and related metastatic sites: implications for clinical practice. Oncologist 2008;13:12705.
  • 44
    Verhoef C, van der Pool AE, Nuyttens JJ, et al. The “liver-first approach” for patients with locally advanced rectal cancer and synchronous liver metastases. Dis Colon Rectum 2009;52:2330.
  • 45
    Gattenlohner S, Germer C, Muller-Hermelink HK. K-ras mutations and cetuximab in colorectal cancer. N Engl J Med 2009;360:835; author reply -6.
  • 46
    Watanabe T, Kobunai T, Yamamoto Y, et al. Heterogeneity of KRAS status may explain the subset of discordant KRAS status between primary and metastatic colorectal cancer. Dis Colon Rectum 2011;54:11708.
  • 47
    Schiro PG, Zhao M, Kuo JS, et al. Sensitive and high-throughput isolation of rare cells from peripheral blood with ensemble-decision aliquot ranking. Angew Chem Int Ed Engl 2012.
  • 48
    DEPArray. Available at:
  • 49
    Saucedo-Zeni N, Mewes S, Niestroj R, et al. A novel method for the in vivo isolation of circulating tumor cells from peripheral blood of cancer patients using a functionalized and structured medical wire. Int J Oncol 2012.
  • 50
    Mostert B, Kraan J, Bolt-de Vries J, et al. Detection of circulating tumor cells in breast cancer may improve through enrichment with anti-CD146. Breast Cancer Res Treat 2011;127:3341.
  • 51
    Hindson BJ, Ness KD, Masquelier DA, et al. High-throughput droplet digital PCR system for absolute quantitation of DNA copy number. Anal Chem 2011;83:860410.
  • 52
    Larsson C, Grundberg I, Soderberg O, et al. In situ detection and genotyping of individual mRNA molecules. Nat Methods 2010;7:3957.