Fumagalli et al. BMC Cancer 2010, 10:101 http://www.biomedcentral.com/1471-2407/10/101 of MET targeted therapies were able to prevent MET signaling, decrease cell viability, and limit cell motility and migration in vitro [32]. The small molecule ARQ 197, a kinase inhibitor, has entered phase II clinical trials so may represent a possible therapeutic strategy for some colon tumors. To our knowledge, this is also one of the most exhaustive analyses of mutation profiling of metastatic lymph nodes and their corresponding primary colon tumors. Our analysis showed that a majority of samples were concordant (89.7%) but in a few samples mutations were detected only in the primary tumor and not in the metastatic lymph node. Also in samples with 2 co- occurring mutations, the ratio of the double mutations varied in primary and lymph node tumors. Discordance in the genetic profile between primary tumors and the metastatic lymph nodes has been observed [33]. Such data may indicate that tumor cell migration selects dif- ferent cell populations from the one in the primary tumor. However, it is also possible that these mutational differences between the lymph node and the primary tumor are a result of tumor heterogeneity. Another interesting observation in our study was that BRAF mutations were significantly correlated with poorly differentiated tumors and the prevalence of mucin; similar observations have been reported [25,26]. These characteristics are both associated with a worse prognosis and are consistent with other reports associat- ing BRAF mutations with a bad prognosis [3]. However, in our study we found that there were 2 metastatic lymph nodes that did not maintain the BRAF mutation present in the corresponding primary tumor, suggesting that BRAF mutations are not essential for metastatic spread to the lymph node in all tumors. Clearly, addi- tional studies would be required to understand these apparent inconsistencies; additional lymph node samples are not currently available but could be the subject of further studies when samples become available [3]. Conclusions The Sequenom platform provided a superior technology for the screening of 238 common hot spot cancer muta- tions in 19 genes. The frequent occurrence of KRAS, PIK3CA, and BRAF was confirmed, and mutations not detected before in colon cancer were found in MET and ABL1. Twenty-five assays from the OncoCarta were replexed to form a new panel, termed ColoCarta, which will be used to screen an additional 800 tumors from NSABP clinical trial C0-7 with the purpose of identify- ing prognostic or predictive markers for stage II and III colon cancer. Note Added in Proof: Although MET-R988C and MET-T1010I mutations were listed in COSMIC as somatic cancer mutations, these nucleotide changes Page 13 of 14 correspond to SNPs rs34589476 and rs56391007 in the NCBI SNP data base, respectively. The frequency for these SNPs is unknown so whether these nucleotide changes are associated with cancer is unknown. Acknowledgements The authors would like to thank Melanie Finnigan, Bill Hiller, and Theresa Oeler for help in cutting and cataloging slides, and Hema Liyanage from Sequenom for replexing the assays. This study was supported by Public Health Service grants U10-CA-37377, U10-CA-69974, U10-CA-12027, and U10- CA-69651 from the National Cancer Institute, National Institutes of Health, and Department of Health and Human Services. This project is funded, in part, under a grant with the Pennsylvania Department of Health. The Department specifically disclaims responsibility for any analyses, interpretations or conclusions. The authors retain the right to provide a copy of the final manuscript to the NIH upon acceptance for journal publication, for public archiving in PubMed Central as soon as possible but no later than 12 months after publication by the journal. Authors’ contributions DF and PGG designed and carried out the experiments and participated in the drafting of the manuscript. YT graded tumors with regard to the degree of differentiation, mucin content, and defined tumor regions, S-IK carried out experiments. H-JC defined the tumor regions; SP participated in the coordination of the study; KLP-G designed and coordinated the study and drafted the manuscript. All authors have given final approval of the version to be published. Competing interests The authors declare that they have no competing interests. Received: 12 August 2009 Accepted: 16 March 2010 Published: 16 March 2010 References 1. Ogino S, Nosho K, Kirkner GJ, Shima K, Irahara N, Kure S, Chan AT, Engelman JA, Kraft P, Cantley LC, et al: PIK3CA Mutation Is Associated With Poor Prognosis Among Patients With Curatively Resected Colon Cancer. J Clin Oncol 2009. 2. Andreyev HJ, Norman AR, Cunningham D, Oates J, Dix BR, Iacopetta BJ, Young J, Walsh T, Ward R, Hawkins N, et al: Kirsten ras mutations in patients with colorectal cancer: the ‘RASCAL II’ study. Br J Cancer 2001, 85(5):692-696. 3. Samowitz WS, Sweeney C, Herrick J, Albertsen H, Levin TR, Murtaugh MA, Wolff RK, Slattery ML: Poor Survival Associated with the BRAF V600E Mutation in Microsatellite-Stable Colon Cancers. Cancer Res 2005, 65(14):6063-6069. 4. Ogino S, Nosho K, Kirkner GJ, Kawasaki T, Meyerhardt JA, Loda M, Giovannucci EL, Fuchs CS: CpG island methylator phenotype, microsatellite instability, BRAF mutation and clinical outcome in colon cancer. Gut 2009, 58(1):90-96. 5. Conlin A, Smith G, Carey FA, Wolf CR, Steele RJC: The prognostic significance of K-ras, p53, and APC mutations in colorectal carcinoma. Gut 2005, 54(9):1283-1286. 6. Barault L, Veyrie N, Jooste V, Lecorre D, Chapusot C, Ferraz JM, Lievre A, Cortet M, Bouvier AM, Rat P, 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(10):2255-2259. 7. Khambata-Ford S, Garrett CR, Meropol NJ, Basik M, Harbison CT, Wu S, Wong TW, Huang X, Takimoto CH, Godwin AK, 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(22):3230-3237. 8. Linardou H, Dahabreh IJ, Kanaloupiti D, Siannis F, Bafaloukos D, Kosmidis P, Papadimitriou CA, Murray S: Assessment of somatic k-RAS mutations as a mechanism associated with resistance to EGFR-targeted agents: a systematic review and meta-analysis of studies in advanced non-small-