Fumagalli et al. BMC Cancer 2010, 10:101 http://www.biomedcentral.com/1471-2407/10/101 Table 2 Frequency of colon cancer mutations Page 9 of 14 No. Mutated Samples Frequency in Primary Tumor* in COSMIC† Multiple Mutations‡ Mutation ABL1-F359V ABL1 Total AKT1-E17K AKT1 Total BRAF-D594V| G BRAF-V600E BRAF Total KRAS-G12A KRAS-G12C KRAS-G12D KRAS-G12R KRAS-G12S KRAS-G12V KRAS-G13D KRAS-A59T KRAS-Q61L KRAS-Q61R KRAS Total MET-R970C MET-T992I MET Total NRAS-G12C NRAS-G12D NRAS-G13R NRAS-G13V NRAS-Q61H NRAS-Q61K NRAS Total PIK3CA-R88Q PIK3CA-C420R PIK3CA-E542K PIK3CA-E545K PIK3CA-Q546K PIK3CA-H701P PIK3CA-H1047L PIK3CA-H1047R PIK3CA Total 1 1 1 1 1 28 29 2 10 40 3 3 20 23 1 1 1 104 2 6 8 1 4 1 1 1 1 9 5 2 9 12 4 1 1 14 48 0.40% 0.40% 0.40% 0.40% 0.40% 11.70% 12.10% 0.80% 4.20% 16.70% 1.30% 1.30% 8.40% 9.60% 0.40% 0.40% 0.40% 43.50% 0.80% 2.50% 3.30% 0.40% 1.70% 0.40% 0.40% 0.40% 0.40% 3.80% 2.10% 0.80% 3.80% 5.00% 1.70% 0.40% 0.40% 5.90% 20.10% 0/66§ NF(0/66)§ 0/31§ NF(0/31)§ NF (0/3179) 14.60% 14.70% 1.80% 3.60% 13.20% 0.40% 4.20% 7.40% 5.20% 0.10% 0.20% NF (0/1927) 36.10% NF (0/77) NF (0/77) 0% NF (0/46) NF (0/46) NF (0/46) NF (0/46) NF (0/46) NF (0/46) 2.2% NF (0/171) NF (0/171) 4.10% 4.10% 1.20% NF (0/171) 1.80% 5.30% 16.40% 100% 100% 24% 34% 50% 38% 80% *% of C-07 samples with this mutation. †Data from COSMIC for colon adenocarcinoma limited to the same mutations interrogated with OncoCarta. The mutations listed are only the ones found in C-07. Some COSMIC amino acid changes are not shown here if they were not mutated in C-07. ‡% of samples with a mutation in the gene shown and at least one other mutation in C-07 samples. §COSMIC data are from large intestine, not specific to colon. frequent of which was KRAS; other mutated genes were BRAF, MET, NRAS, and a second PIK3CA muta- tion (Table 2, last column). Tumors with MET and NRAS mutations also have an unexpectedly high fre- quency of co-occurring mutations, which suggests that they occur as a second mutation and perhaps later in the etiology of the tumor. Many tumors contain only a KRAS or BRAF mutation, which is consistent with pre- vious reports finding these mutations in earlier stages of colon cancer [23,24]. The multiple mutation fre- quencies for tumors with KRAS and PIK3CA or with PIK3CA and BRAF were slightly higher and lower, respectively, than expected based on their individual frequencies (Table 4). Conversely, the expected double mutation frequency of BRAF and KRAS would be 5.1%, based on our data, but this combination was not found, also in agreement with previous reports [24] (Table 4).