Mutation Analysis (MutSig v2.0)
Thyroid Adenocarcinoma (Primary solid tumor)
21 April 2013  |  analyses__2013_04_21
Maintainer Information
Citation Information
doi:10.7908/C1FT8J1G
Maintained by Dan DiCara (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2013): Thyroid Adenocarcinoma (Primary solid tumor cohort) - 21 April 2013: Mutation Analysis (MutSig v2.0). Broad Institute of MIT and Harvard. doi:10.7908/C1FT8J1G
Overview
Introduction

This report serves to describe the mutational landscape and properties of a given individual set, as well as rank genes and genesets according to mutational significance. MutSig v2.0 was used to generate the results found in this report.

  • Working with individual set: THCA-TP

  • Number of patients in set: 323

Input

The input for this pipeline is a set of individuals with the following files associated for each:

  1. An annotated .maf file describing the mutations called for the respective individual, and their properties.

  2. A .wig file that contains information about the coverage of the sample.

Summary

  • MAF used for this analysis:THCA-TP.final_analysis_set.maf

  • Significantly mutated genes (q ≤ 0.1): 36

  • Mutations seen in COSMIC: 249

  • Significantly mutated genes in COSMIC territory: 11

  • Genes with clustered mutations (≤ 3 aa apart): 47

  • Significantly mutated genesets: 72

  • Significantly mutated genesets: (excluding sig. mutated genes):0

Mutation Preprocessing

  • Read 323 MAFs of type "Broad"

  • Total number of mutations in input MAFs: 11952

  • After removing 99 mutations outside chr1-24: 11853

  • After removing 1530 blacklisted mutations: 10323

  • After removing 3226 noncoding mutations: 7097

Mutation Filtering

  • Number of mutations before filtering: 7097

  • After removing 289 mutations outside gene set: 6808

  • After removing 2 mutations outside category set: 6806

Results
Breakdown of Mutations by Type

Table 1.  Get Full Table Table representing breakdown of mutations by type.

type count
Frame_Shift_Del 375
Frame_Shift_Ins 112
In_Frame_Del 254
In_Frame_Ins 18
Missense_Mutation 4143
Nonsense_Mutation 194
Nonstop_Mutation 4
Silent 1573
Splice_Site 125
Translation_Start_Site 8
Total 6806
Breakdown of Mutation Rates by Category Type

Table 2.  Get Full Table A breakdown of mutation rates per category discovered for this individual set.

category n N rate rate_per_mb relative_rate exp_ns_s_ratio
*CpG->T 782 526711238 1.5e-06 1.5 2.7 2.1
*Cp(A/C/T)->T 981 4313476957 2.3e-07 0.23 0.41 1.7
A->G 826 4649186676 1.8e-07 0.18 0.32 2.3
transver 1558 9489374871 1.6e-07 0.16 0.3 5
indel+null 1084 9489374871 1.1e-07 0.11 0.21 NaN
double_null 2 9489374871 2.1e-10 0.00021 0.00038 NaN
Total 5233 9489374871 5.5e-07 0.55 1 3.5
Target Coverage for Each Individual

The x axis represents the samples. The y axis represents the exons, one row per exon, and they are sorted by average coverage across samples. For exons with exactly the same average coverage, they are sorted next by the %GC of the exon. (The secondary sort is especially useful for the zero-coverage exons at the bottom).

Figure 1. 

Distribution of Mutation Counts, Coverage, and Mutation Rates Across Samples

Figure 2.  Patients counts and rates file used to generate this plot: THCA-TP.patients.counts_and_rates.txt

CoMut Plot

Figure 3.  Get High-res Image The matrix in the center of the figure represents individual mutations in patient samples, color-coded by type of mutation, for the significantly mutated genes. The rate of synonymous and non-synonymous mutations is displayed at the top of the matrix. The barplot on the left of the matrix shows the number of mutations in each gene. The percentages represent the fraction of tumors with at least one mutation in the specified gene. The barplot to the right of the matrix displays the q-values for the most significantly mutated genes. The purple boxplots below the matrix (only displayed if required columns are present in the provided MAF) represent the distributions of allelic fractions observed in each sample. The plot at the bottom represents the base substitution distribution of individual samples, using the same categories that were used to calculate significance.

Significantly Mutated Genes

Column Descriptions:

  • N = number of sequenced bases in this gene across the individual set

  • n = number of (nonsilent) mutations in this gene across the individual set

  • npat = number of patients (individuals) with at least one nonsilent mutation

  • nsite = number of unique sites having a non-silent mutation

  • nsil = number of silent mutations in this gene across the individual set

  • n1 = number of nonsilent mutations of type: *CpG->T

  • n2 = number of nonsilent mutations of type: *Cp(A/C/T)->T

  • n3 = number of nonsilent mutations of type: A->G

  • n4 = number of nonsilent mutations of type: transver

  • n5 = number of nonsilent mutations of type: indel+null

  • n6 = number of nonsilent mutations of type: double_null

  • p_classic = p-value for the observed amount of nonsilent mutations being elevated in this gene

  • p_ns_s = p-value for the observed nonsilent/silent ratio being elevated in this gene

  • p_cons = p-value for enrichment of mutations at evolutionarily most-conserved sites in gene

  • p_joint = p-value for clustering + conservation

  • p = p-value (overall)

  • q = q-value, False Discovery Rate (Benjamini-Hochberg procedure)

Table 3.  Get Full Table A Ranked List of Significantly Mutated Genes. Number of significant genes found: 36. Number of genes displayed: 35. Click on a gene name to display its stick figure depicting the distribution of mutations and mutation types across the chosen gene (this feature may not be available for all significant genes).

rank gene description N n npat nsite nsil n1 n2 n3 n4 n5 n6 p_classic p_ns_s p_cons p_joint p q
1 BRAF v-raf murine sarcoma viral oncogene homolog B1 718092 183 183 2 1 0 0 1 182 0 0 <1.00e-15 5e-14 0 0 <1.00e-15 <3.62e-12
2 NRAS neuroblastoma RAS viral (v-ras) oncogene homolog 189273 26 26 2 0 0 0 20 6 0 0 4.33e-15 0.00016 0.0022 0 <1.00e-15 <3.62e-12
3 HRAS v-Ha-ras Harvey rat sarcoma viral oncogene homolog 209181 12 12 2 0 0 0 9 3 0 0 1.95e-14 0.13 0.0012 0 <1.00e-15 <3.62e-12
4 EMG1 EMG1 nucleolar protein homolog (S. cerevisiae) 220090 6 6 2 0 0 0 0 0 6 0 8.48e-10 1 0.91 0 <1.00e-15 <3.62e-12
5 PTTG1IP pituitary tumor-transforming 1 interacting protein 144700 4 4 1 0 0 0 0 0 4 0 1.48e-06 1 0.00056 0 <1.00e-15 <3.62e-12
6 RPTN repetin 763230 8 8 6 0 0 0 1 0 7 0 5.57e-09 0.65 0.19 0.0011 1.60e-10 4.82e-07
7 EIF1AX eukaryotic translation initiation factor 1A, X-linked 142447 6 5 5 0 0 4 0 1 1 0 7.17e-10 0.24 0.041 0.026 4.80e-10 1.24e-06
8 CCDC15 coiled-coil domain containing 15 671425 5 5 1 1 0 0 0 5 0 0 2.31e-05 0.72 1 7.6e-06 4.13e-09 9.33e-06
9 ZNF845 zinc finger protein 845 928346 6 6 3 0 0 3 3 0 0 0 3.81e-06 0.09 1 0.000053 4.73e-09 9.51e-06
10 ZNF878 zinc finger protein 878 523994 4 4 2 0 0 0 0 4 0 0 0.000105 0.54 1 0.000018 4.02e-08 7.28e-05
11 TG thyroglobulin 2717568 16 16 16 3 1 0 1 4 10 0 1.13e-08 0.82 0.56 0.22 5.30e-08 8.71e-05
12 PRB2 proline-rich protein BstNI subfamily 2 405776 6 6 4 1 0 1 0 2 3 0 5.76e-08 0.65 0.65 0.1 1.16e-07 0.000175
13 R3HDM2 R3H domain containing 2 634652 4 4 1 0 0 0 0 0 4 0 0.000381 1 0.99 0.000037 2.71e-07 0.000378
14 IL32 interleukin 32 168065 3 3 1 0 0 0 0 0 3 0 1.65e-05 1 0.92 0.0013 3.88e-07 0.000502
15 TMCO2 transmembrane and coiled-coil domains 2 179663 3 3 1 0 0 0 0 0 3 0 6.72e-05 1 0.94 0.00089 1.05e-06 0.00127
16 PPTC7 PTC7 protein phosphatase homolog (S. cerevisiae) 230856 3 3 1 0 0 0 0 0 3 0 0.000200 1 0.96 0.00043 1.47e-06 0.00166
17 MUC7 mucin 7, secreted 368847 5 5 5 1 0 2 2 0 1 0 4.15e-07 0.41 0.11 0.22 1.60e-06 0.00170
18 LYPD3 LY6/PLAUR domain containing 3 337331 3 3 1 0 0 0 0 0 3 0 0.000376 1 0.76 0.00042 2.65e-06 0.00267
19 TMEM90B 254847 3 3 1 0 0 0 0 0 3 0 0.000355 1 0.87 0.00059 3.44e-06 0.00319
20 ACRC acidic repeat containing 609349 4 2 2 0 0 2 0 2 0 0 0.00982 0.37 0.76 0.000022 3.53e-06 0.00319
21 ZNF799 zinc finger protein 799 607484 5 5 2 1 0 0 5 0 0 0 7.23e-06 0.26 0.99 0.034 4.03e-06 0.00347
22 PPM1D protein phosphatase 1D magnesium-dependent, delta isoform 502843 5 5 5 0 0 1 0 0 4 0 4.52e-06 0.7 0.86 0.095 6.71e-06 0.00552
23 MAP3K3 mitogen-activated protein kinase kinase kinase 3 653710 4 4 4 0 0 2 0 1 1 0 0.000227 0.28 0.27 0.0045 1.51e-05 0.0119
24 TROAP trophinin associated protein (tastin) 787729 5 3 3 0 0 1 2 2 0 0 0.00705 0.17 1 0.00018 1.84e-05 0.0139
25 SYNPO2L synaptopodin 2-like 692797 3 3 1 0 0 0 3 0 0 0 0.00179 0.27 0.01 0.00079 2.05e-05 0.0148
26 ATAD2 ATPase family, AAA domain containing 2 1353048 4 4 3 0 0 1 1 0 2 0 0.00417 0.45 0.2 0.00036 2.17e-05 0.0151
27 NLRP6 NLR family, pyrin domain containing 6 591829 2 2 1 0 0 0 2 0 0 0 0.00859 0.69 0.00085 0.00022 2.73e-05 0.0183
28 KRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog 224332 3 3 3 0 0 0 1 2 0 0 0.000128 0.48 0.017 0.025 4.40e-05 0.0284
29 SLC5A11 solute carrier family 5 (sodium/glucose cotransporter), member 11 673160 3 3 1 0 0 0 0 0 3 0 0.00546 1 0.93 0.00062 4.59e-05 0.0286
30 SCUBE2 signal peptide, CUB domain, EGF-like 2 953936 3 3 1 0 0 0 0 0 3 0 0.00622 1 0.99 0.00062 5.17e-05 0.0304
31 PRG4 proteoglycan 4 1374896 7 4 7 1 0 1 1 2 3 0 0.00366 0.55 0.99 0.0011 5.20e-05 0.0304
32 ZNF479 zinc finger protein 479 507416 3 3 1 0 0 0 0 3 0 0 0.00185 0.65 1 0.0028 6.74e-05 0.0381
33 SREBF2 sterol regulatory element binding transcription factor 2 983587 3 3 2 0 0 1 0 0 2 0 0.00351 0.59 0.98 0.0038 0.000163 0.0892
34 OR56A1 olfactory receptor, family 56, subfamily A, member 1 309928 2 2 2 0 1 1 0 0 0 0 0.00298 0.34 0.0042 0.0049 0.000176 0.0919
35 MED31 mediator complex subunit 31 131968 2 2 2 1 0 0 0 1 1 0 0.000178 0.96 NaN NaN 0.000178 0.0919
BRAF

Figure S1.  This figure depicts the distribution of mutations and mutation types across the BRAF significant gene.

NRAS

Figure S2.  This figure depicts the distribution of mutations and mutation types across the NRAS significant gene.

HRAS

Figure S3.  This figure depicts the distribution of mutations and mutation types across the HRAS significant gene.

EMG1

Figure S4.  This figure depicts the distribution of mutations and mutation types across the EMG1 significant gene.

PTTG1IP

Figure S5.  This figure depicts the distribution of mutations and mutation types across the PTTG1IP significant gene.

RPTN

Figure S6.  This figure depicts the distribution of mutations and mutation types across the RPTN significant gene.

EIF1AX

Figure S7.  This figure depicts the distribution of mutations and mutation types across the EIF1AX significant gene.

CCDC15

Figure S8.  This figure depicts the distribution of mutations and mutation types across the CCDC15 significant gene.

ZNF845

Figure S9.  This figure depicts the distribution of mutations and mutation types across the ZNF845 significant gene.

ZNF878

Figure S10.  This figure depicts the distribution of mutations and mutation types across the ZNF878 significant gene.

TG

Figure S11.  This figure depicts the distribution of mutations and mutation types across the TG significant gene.

R3HDM2

Figure S12.  This figure depicts the distribution of mutations and mutation types across the R3HDM2 significant gene.

IL32

Figure S13.  This figure depicts the distribution of mutations and mutation types across the IL32 significant gene.

TMCO2

Figure S14.  This figure depicts the distribution of mutations and mutation types across the TMCO2 significant gene.

PPTC7

Figure S15.  This figure depicts the distribution of mutations and mutation types across the PPTC7 significant gene.

MUC7

Figure S16.  This figure depicts the distribution of mutations and mutation types across the MUC7 significant gene.

LYPD3

Figure S17.  This figure depicts the distribution of mutations and mutation types across the LYPD3 significant gene.

ACRC

Figure S18.  This figure depicts the distribution of mutations and mutation types across the ACRC significant gene.

ZNF799

Figure S19.  This figure depicts the distribution of mutations and mutation types across the ZNF799 significant gene.

PPM1D

Figure S20.  This figure depicts the distribution of mutations and mutation types across the PPM1D significant gene.

MAP3K3

Figure S21.  This figure depicts the distribution of mutations and mutation types across the MAP3K3 significant gene.

TROAP

Figure S22.  This figure depicts the distribution of mutations and mutation types across the TROAP significant gene.

SYNPO2L

Figure S23.  This figure depicts the distribution of mutations and mutation types across the SYNPO2L significant gene.

ATAD2

Figure S24.  This figure depicts the distribution of mutations and mutation types across the ATAD2 significant gene.

NLRP6

Figure S25.  This figure depicts the distribution of mutations and mutation types across the NLRP6 significant gene.

KRAS

Figure S26.  This figure depicts the distribution of mutations and mutation types across the KRAS significant gene.

SLC5A11

Figure S27.  This figure depicts the distribution of mutations and mutation types across the SLC5A11 significant gene.

SCUBE2

Figure S28.  This figure depicts the distribution of mutations and mutation types across the SCUBE2 significant gene.

PRG4

Figure S29.  This figure depicts the distribution of mutations and mutation types across the PRG4 significant gene.

ZNF479

Figure S30.  This figure depicts the distribution of mutations and mutation types across the ZNF479 significant gene.

SREBF2

Figure S31.  This figure depicts the distribution of mutations and mutation types across the SREBF2 significant gene.

OR56A1

Figure S32.  This figure depicts the distribution of mutations and mutation types across the OR56A1 significant gene.

COSMIC analyses

In this analysis, COSMIC is used as a filter to increase power by restricting the territory of each gene. Cosmic version: v48.

Table 4.  Get Full Table Significantly mutated genes (COSMIC territory only). To access the database please go to: COSMIC. Number of significant genes found: 11. Number of genes displayed: 10

rank gene description n cos n_cos N_cos cos_ev p q
1 HRAS v-Ha-ras Harvey rat sarcoma viral oncogene homolog 12 19 12 6137 2496 2.5e-13 9.6e-10
2 NRAS neuroblastoma RAS viral (v-ras) oncogene homolog 26 33 26 10659 33748 4.3e-13 9.6e-10
3 BRAF v-raf murine sarcoma viral oncogene homolog B1 183 89 183 28747 2630268 1.1e-12 1.7e-09
4 KRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog 3 52 3 16796 14910 1.3e-07 0.00015
5 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 3 220 3 71060 51 9.7e-06 0.0088
6 C4BPA complement component 4 binding protein, alpha 1 1 1 323 1 0.00018 0.073
7 PCGF2 polycomb group ring finger 2 2 1 1 323 1 0.00018 0.073
8 SEZ6L seizure related 6 homolog (mouse)-like 2 1 1 323 1 0.00018 0.073
9 SMC3 structural maintenance of chromosomes 3 1 1 1 323 1 0.00018 0.073
10 TNFRSF9 tumor necrosis factor receptor superfamily, member 9 1 1 1 323 1 0.00018 0.073

Note:

n - number of (nonsilent) mutations in this gene across the individual set.

cos = number of unique mutated sites in this gene in COSMIC

n_cos = overlap between n and cos.

N_cos = number of individuals times cos.

cos_ev = total evidence: number of reports in COSMIC for mutations seen in this gene.

p = p-value for seeing the observed amount of overlap in this gene)

q = q-value, False Discovery Rate (Benjamini-Hochberg procedure)

Clustered Mutations

Table 5.  Get Full Table Genes with Clustered Mutations

num gene desc n mindist nmuts0 nmuts3 nmuts12 npairs0 npairs3 npairs12
353 BRAF v-raf murine sarcoma viral oncogene homolog B1 183 0 16471 16653 16653 16471 16653 16653
2198 NRAS neuroblastoma RAS viral (v-ras) oncogene homolog 26 0 325 325 325 325 325 325
1472 HRAS v-Ha-ras Harvey rat sarcoma viral oncogene homolog 12 0 66 66 66 66 66 66
541 CCDC15 coiled-coil domain containing 15 5 0 10 10 10 10 10 10
3779 ZNF799 zinc finger protein 799 5 0 6 6 6 6 6 6
3788 ZNF845 zinc finger protein 845 6 0 6 6 6 6 6 6
1015 EIF1AX eukaryotic translation initiation factor 1A, X-linked 6 0 4 7 7 4 7 7
1124 FAM47C family with sequence similarity 47, member C 5 0 3 3 3 3 3 3
3175 SYNPO2L synaptopodin 2-like 3 0 3 3 3 3 3 3
3714 ZNF443 zinc finger protein 443 4 0 3 3 3 3 3 3

Note:

n - number of mutations in this gene in the individual set.

mindist - distance (in aa) between closest pair of mutations in this gene

npairs3 - how many pairs of mutations are within 3 aa of each other.

npairs12 - how many pairs of mutations are within 12 aa of each other.

Geneset Analyses

Table 6.  Get Full Table A Ranked List of Significantly Mutated Genesets. (Source: MSigDB GSEA Cannonical Pathway Set).Number of significant genesets found: 72. Number of genesets displayed: 10

rank geneset description genes N_genes mut_tally N n npat nsite nsil n1 n2 n3 n4 n5 n6 p_ns_s p q
1 HSA04810_REGULATION_OF_ACTIN_CYTOSKELETON Genes involved in regulation of actin cytoskeleton ABI2, ACTN1, ACTN2, ACTN3, ACTN4, APC, APC2, ARAF, ARHGEF1, ARHGEF12, ARHGEF4, ARHGEF6, ARHGEF7, ARPC1A, ARPC1B, ARPC2, ARPC3, ARPC4, ARPC5, ARPC5L, BAIAP2, BCAR1, BDKRB1, BDKRB2, BRAF, C3orf10, CD14, CDC42, CFL1, CFL2, CHRM1, CHRM2, CHRM3, CHRM4, CHRM5, CRK, CRKL, CSK, CYFIP1, CYFIP2, DIAPH1, DIAPH2, DIAPH3, DOCK1, EGF, EGFR, EZR, F2, F2R, FGD1, FGD3, FGF1, FGF10, FGF11, FGF12, FGF13, FGF14, FGF16, FGF17, FGF18, FGF19, FGF2, FGF20, FGF21, FGF22, FGF23, FGF3, FGF4, FGF5, FGF6, FGF7, FGF8, FGF9, FGFR1, FGFR2, FGFR3, FGFR4, FN1, GIT1, GNA12, GNA13, GNG12, GRLF1, GSN, HRAS, INS, IQGAP1, IQGAP2, IQGAP3, ITGA1, ITGA10, ITGA11, ITGA2, ITGA2B, ITGA3, ITGA4, ITGA5, ITGA6, ITGA7, ITGA8, ITGA9, ITGAD, ITGAE, ITGAL, ITGAM, ITGAV, ITGAX, ITGB1, ITGB2, ITGB3, ITGB4, ITGB5, ITGB6, ITGB7, ITGB8, KRAS, LIMK1, LIMK2, LOC200025, LOC645126, LOC653888, MAP2K1, MAP2K2, MAPK1, MAPK3, MLCK, MOS, MRAS, MRCL3, MRLC2, MSN, MYH10, MYH14, MYH9, MYL2, MYL5, MYL7, MYL8P, MYL9, MYLC2PL, MYLK, MYLK2, MYLPF, NCKAP1, NCKAP1L, NRAS, PAK1, PAK2, PAK3, PAK4, PAK6, PAK7, PDGFA, PDGFB, PDGFRA, PDGFRB, PFN1, PFN2, PFN3, PFN4, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PIP4K2A, PIP4K2B, PIP4K2C, PIP5K1A, PIP5K1B, PIP5K1C, PIP5K3, PPP1CA, PPP1CB, PPP1CC, PPP1R12A, PPP1R12B, PTK2, PXN, RAC1, RAC2, RAC3, RAF1, RDX, RHOA, ROCK1, ROCK2, RRAS, RRAS2, SCIN, SLC9A1, SOS1, SOS2, SSH1, SSH2, SSH3, TIAM1, TIAM2, TMSB4X, TMSB4Y, TMSL3, VAV1, VAV2, VAV3, VCL, WAS, WASF1, WASF2, WASL 202 ABI2(2), APC(1), ARHGEF4(1), ARHGEF6(1), ARHGEF7(2), BRAF(183), CDC42(1), CHRM3(1), CHRM4(1), CHRM5(1), EZR(1), FGD1(1), FGD3(1), FGF20(1), FGF7(1), FN1(1), HRAS(12), IQGAP1(2), ITGA10(1), ITGA3(2), ITGA8(1), ITGAD(2), ITGAL(4), ITGAM(2), ITGB1(2), ITGB3(1), ITGB4(1), ITGB8(1), KRAS(3), MYH10(3), MYH14(1), MYH9(1), MYLK(2), NCKAP1L(1), NRAS(26), PAK3(1), PAK7(1), PDGFRB(1), PIK3CA(3), PIK3CB(1), PIK3CG(1), PIK3R1(1), PIK3R5(3), PIP4K2B(1), PIP4K2C(1), PIP5K1A(1), SOS1(1), TIAM2(3), VAV2(1), VCL(1) 133274235 289 243 73 27 9 18 38 210 14 0 3.89e-09 <1.00e-15 <1.50e-13
2 ST_ADRENERGIC Adrenergic receptors respond to epinephrine and norepinephrine signaling. AKT1, APC, AR, ASAH1, BF, BRAF, CAMP, CCL13, CCL15, CCL16, DAG1, EGFR, GAS, GNA11, GNA15, GNAI1, GNAQ, ITPKA, ITPKB, ITPR1, ITPR2, ITPR3, KCNJ3, KCNJ5, KCNJ9, MAPK1, MAPK10, MAPK14, PHKA2, PIK3CA, PIK3CD, PIK3R1, PITX2, PTX1, PTX3, RAF1, SRC 34 APC(1), AR(1), BRAF(183), GNA15(1), ITPR1(2), ITPR2(4), MAPK10(1), PHKA2(2), PIK3CA(3), PIK3R1(1), PITX2(1), SRC(1) 25744051 201 190 20 5 5 2 1 189 4 0 3.78e-11 <1.00e-15 <1.50e-13
3 HSA04320_DORSO_VENTRAL_AXIS_FORMATION Genes involved in dorso-ventral axis formation BRAF, CPEB1, EGFR, ERBB2, ERBB4, ETS1, ETS2, ETV6, ETV7, FMN2, GRB2, KRAS, MAP2K1, MAPK1, MAPK3, NOTCH1, NOTCH2, NOTCH3, NOTCH4, PIWIL1, PIWIL2, PIWIL3, PIWIL4, RAF1, SOS1, SOS2, SPIRE1, SPIRE2 28 BRAF(183), ERBB2(1), ETS1(2), KRAS(3), NOTCH2(1), NOTCH4(1), PIWIL2(1), SOS1(1) 25185488 193 188 12 5 1 2 4 186 0 0 4.14e-11 <1.00e-15 <1.50e-13
4 ST_G_ALPHA_S_PATHWAY The G-alpha-s protein activates adenylyl cyclases, which catalyze cAMP formation. ASAH1, BF, BFAR, BRAF, CAMP, CREB1, CREB3, CREB5, EPAC, GAS, GRF2, MAPK1, RAF1, SNX13, SRC, TERF2IP 12 BFAR(1), BRAF(183), SNX13(1), SRC(1), TERF2IP(1) 5335473 187 184 6 2 0 0 1 183 3 0 2.63e-12 1.11e-15 1.50e-13
5 HSA04730_LONG_TERM_DEPRESSION Genes involved in long-term depression ARAF, BRAF, C7orf16, CACNA1A, CRH, CRHR1, GNA11, GNA12, GNA13, GNAI1, GNAI2, GNAI3, GNAO1, GNAQ, GNAS, GNAZ, GRIA1, GRIA2, GRIA3, GRID2, GRM1, GRM5, GUCY1A2, GUCY1A3, GUCY1B3, GUCY2C, GUCY2D, GUCY2F, HRAS, IGF1, IGF1R, ITPR1, ITPR2, ITPR3, KRAS, LYN, MAP2K1, MAP2K2, MAPK1, MAPK3, NOS1, NOS2A, NOS3, NPR1, NPR2, NRAS, PLA2G10, PLA2G12A, PLA2G12B, PLA2G1B, PLA2G2A, PLA2G2D, PLA2G2E, PLA2G2F, PLA2G3, PLA2G4A, PLA2G5, PLA2G6, PLCB1, PLCB2, PLCB3, PLCB4, PPP2CA, PPP2CB, PPP2R1A, PPP2R1B, PPP2R2A, PPP2R2B, PPP2R2C, PRKCA, PRKCB1, PRKCG, PRKG1, PRKG2, RAF1, RYR1 74 BRAF(183), CACNA1A(2), GNAS(3), GRIA1(1), GRIA2(2), GRM1(3), HRAS(12), IGF1R(1), ITPR1(2), ITPR2(4), KRAS(3), NPR1(1), NRAS(26), PLA2G5(1), PLCB2(1), PPP2R1A(2), PRKG1(1), RYR1(4) 53048814 252 234 36 8 9 5 32 203 3 0 3.60e-14 1.22e-15 1.50e-13
6 HSA04650_NATURAL_KILLER_CELL_MEDIATED_CYTOTOXICITY Genes involved in natural killer cell mediated cytotoxicity ARAF, BID, BRAF, CASP3, CD244, CD247, CD48, CHP, CSF2, FAS, FASLG, FCER1G, FCGR3A, FCGR3B, FYN, GRB2, GZMB, HCST, HLA-A, HLA-B, HLA-C, HLA-E, HLA-G, HRAS, ICAM1, ICAM2, IFNA1, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA2, IFNA21, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNAR1, IFNAR2, IFNB1, IFNG, IFNGR1, IFNGR2, ITGAL, ITGB2, KIR2DL1, KIR2DL2, KIR2DL3, KIR2DL4, KIR2DL5A, KIR2DS1, KIR2DS2, KIR3DL1, KIR3DL2, KLRC1, KLRC2, KLRC3, KLRD1, KLRK1, KRAS, LAT, LCK, LCP2, LOC652578, MAP2K1, MAP2K2, MAPK1, MAPK3, MICA, MICB, NCR1, NCR2, NCR3, NFAT5, NFATC1, NFATC2, NFATC3, NFATC4, NRAS, PAK1, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PLCG1, PLCG2, PPP3CA, PPP3CB, PPP3CC, PPP3R1, PPP3R2, PRF1, PRKCA, PRKCB1, PRKCG, PTK2B, PTPN11, PTPN6, RAC1, RAC2, RAC3, RAF1, SH2D1A, SH2D1B, SH3BP2, SHC1, SHC2, SHC3, SHC4, SOS1, SOS2, SYK, TNF, TNFRSF10A, TNFRSF10B, TNFRSF10C, TNFRSF10D, TNFSF10, TYROBP, ULBP1, ULBP2, ULBP3, VAV1, VAV2, VAV3, ZAP70 126 BRAF(183), FYN(1), HLA-E(1), HRAS(12), IFNA4(1), IFNAR2(1), IFNGR1(2), ITGAL(4), KIR2DL1(1), KIR3DL1(2), KRAS(3), LCK(1), NCR1(1), NFAT5(1), NFATC1(2), NFATC4(2), NRAS(26), PIK3CA(3), PIK3CB(1), PIK3CG(1), PIK3R1(1), PIK3R5(3), PLCG2(1), PPP3R2(1), PTK2B(1), SHC1(1), SOS1(1), SYK(1), VAV2(1) 54658054 260 231 45 13 7 7 35 205 6 0 1.44e-12 2.00e-15 1.57e-13
7 ST_G_ALPHA_I_PATHWAY Gi and Go proteins are members of the same family that transduce cellular signals through both their alpha and beta subunits. AKT1, AKT2, AKT3, ASAH1, BF, BRAF, DAG1, DRD2, EGFR, EPHB2, GRB2, ITPKA, ITPKB, ITPR1, ITPR2, ITPR3, KCNJ3, KCNJ5, KCNJ9, MAPK1, PI3, PIK3CB, PITX2, PLCB1, PLCB2, PLCB3, PLCB4, RAF1, RAP1GA1, RGS20, SHC1, SOS1, SOS2, SRC, STAT3, TERF2IP 34 BRAF(183), ITPR1(2), ITPR2(4), PIK3CB(1), PITX2(1), PLCB2(1), SHC1(1), SOS1(1), SRC(1), TERF2IP(1) 28143487 196 189 15 3 6 2 1 186 1 0 1.17e-12 2.11e-15 1.57e-13
8 HSA04010_MAPK_SIGNALING_PATHWAY Genes involved in MAPK signaling pathway ACVR1B, ACVR1C, AKT1, AKT2, AKT3, ARRB1, ARRB2, ATF2, ATF4, BDNF, BRAF, CACNA1A, CACNA1B, CACNA1C, CACNA1D, CACNA1E, CACNA1F, CACNA1G, CACNA1H, CACNA1I, CACNA1S, CACNA2D1, CACNA2D2, CACNA2D3, CACNA2D4, CACNB1, CACNB2, CACNB3, CACNB4, CACNG1, CACNG2, CACNG3, CACNG4, CACNG5, CACNG6, CACNG7, CACNG8, CASP3, CD14, CDC25B, CDC42, CHP, CHUK, CRK, CRKL, DAXX, DDIT3, DUSP1, DUSP10, DUSP14, DUSP16, DUSP2, DUSP3, DUSP4, DUSP5, DUSP6, DUSP7, DUSP8, DUSP9, ECSIT, EGF, EGFR, ELK1, ELK4, EVI1, FAS, FASLG, FGF1, FGF10, FGF11, FGF12, FGF13, FGF14, FGF16, FGF17, FGF18, FGF19, FGF2, FGF20, FGF21, FGF22, FGF23, FGF3, FGF4, FGF5, FGF6, FGF7, FGF8, FGF9, FGFR1, FGFR2, FGFR3, FGFR4, FLNA, FLNB, FLNC, FOS, GADD45A, GADD45B, GADD45G, GNA12, GNG12, GRB2, HRAS, IKBKB, IKBKG, IL1A, IL1B, IL1R1, IL1R2, JUN, JUND, KRAS, LOC653852, MAP2K1, MAP2K1IP1, MAP2K2, MAP2K3, MAP2K4, MAP2K5, MAP2K6, MAP2K7, MAP3K1, MAP3K10, MAP3K12, MAP3K13, MAP3K14, MAP3K2, MAP3K3, MAP3K4, MAP3K5, MAP3K6, MAP3K7, MAP3K7IP1, MAP3K7IP2, MAP3K8, MAP4K1, MAP4K2, MAP4K3, MAP4K4, MAPK1, MAPK10, MAPK11, MAPK12, MAPK13, MAPK14, MAPK3, MAPK7, MAPK8, MAPK8IP1, MAPK8IP2, MAPK8IP3, MAPK9, MAPKAPK2, MAPKAPK3, MAPKAPK5, MAPT, MAX, MEF2C, MKNK1, MKNK2, MOS, MRAS, MYC, NF1, NFATC2, NFATC4, NFKB1, NFKB2, NGFB, NLK, NR4A1, NRAS, NTF3, NTF5, NTRK1, NTRK2, PAK1, PAK2, PDGFA, PDGFB, PDGFRA, PDGFRB, PLA2G10, PLA2G12A, PLA2G12B, PLA2G1B, PLA2G2A, PLA2G2D, PLA2G2E, PLA2G2F, PLA2G3, PLA2G4A, PLA2G5, PLA2G6, PPM1A, PPM1B, PPP3CA, PPP3CB, PPP3CC, PPP3R1, PPP3R2, PPP5C, PRKACA, PRKACB, PRKACG, PRKCA, PRKCB1, PRKCG, PRKX, PRKY, PTPN5, PTPN7, PTPRR, RAC1, RAC2, RAC3, RAF1, RAP1A, RAP1B, RAPGEF2, RASA1, RASA2, RASGRF1, RASGRF2, RASGRP1, RASGRP2, RASGRP3, RASGRP4, RPS6KA1, RPS6KA2, RPS6KA3, RPS6KA4, RPS6KA5, RPS6KA6, RRAS, RRAS2, SOS1, SOS2, SRF, STK3, STK4, STMN1, TAOK1, TAOK2, TAOK3, TGFB1, TGFB2, TGFB3, TGFBR1, TGFBR2, TNF, TNFRSF1A, TP53, TRAF2, TRAF6, ZAK 247 ARRB1(1), BRAF(183), CACNA1A(2), CACNA1B(1), CACNA1C(1), CACNA1D(1), CACNA1E(3), CACNA1G(2), CACNA1H(1), CACNA1S(1), CACNA2D1(2), CACNA2D3(1), CACNA2D4(1), CACNB3(1), CDC42(1), DUSP2(1), DUSP5(1), DUSP7(1), DUSP8(1), ECSIT(1), FGF20(1), FGF7(1), FLNA(1), FLNC(3), HRAS(12), IL1R1(2), JUN(1), KRAS(3), MAP2K5(1), MAP2K6(1), MAP3K1(1), MAP3K3(4), MAP3K6(1), MAP3K8(1), MAP4K4(1), MAPK10(1), MAPK8IP2(1), MAPKAPK3(1), MKNK2(1), MYC(1), NF1(5), NFATC4(2), NRAS(26), PDGFRB(1), PLA2G5(1), PPP3R2(1), RASGRF2(1), RASGRP1(1), RPS6KA1(1), SOS1(1), TGFB1(1), TP53(3) 137756696 290 242 75 23 15 14 37 208 16 0 3.98e-11 2.22e-15 1.57e-13
9 HSA04150_MTOR_SIGNALING_PATHWAY Genes involved in mTOR signaling pathway AKT1, AKT2, AKT3, BRAF, CAB39, DDIT4, EIF4B, EIF4EBP1, FIGF, FRAP1, GBL, HIF1A, IGF1, INS, KIAA1303, LYK5, MAPK1, MAPK3, PDPK1, PGF, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PRKAA1, PRKAA2, RHEB, RICTOR, RPS6, RPS6KA1, RPS6KA2, RPS6KA3, RPS6KA6, RPS6KB1, RPS6KB2, STK11, TSC1, TSC2, ULK1, ULK2, ULK3, VEGFA, VEGFB, VEGFC 44 BRAF(183), FIGF(1), PIK3CA(3), PIK3CB(1), PIK3CG(1), PIK3R1(1), PIK3R5(3), RPS6KA1(1), RPS6KB2(1), ULK3(1), VEGFA(1) 25626228 197 186 16 4 1 2 3 187 4 0 1.50e-11 2.33e-15 1.57e-13
10 ST_DIFFERENTIATION_PATHWAY_IN_PC12_CELLS Rat-derived PC12 cells respond to nerve growth factor (NGF) and PACAP to differentiate into neuronal cells. AKT1, ASAH1, ATF1, BRAF, CAMP, CREB1, CREB3, CREB5, CREBBP, CRKL, DAG1, EGR1, EGR2, EGR3, EGR4, ELK1, FRS2, GAS, GNAQ, GRF2, JUN, MAP1B, MAP2K4, MAP2K7, MAPK1, MAPK10, MAPK3, MAPK8, MAPK8IP1, MAPK8IP2, MAPK8IP3, MAPK9, NTRK1, OPN1LW, PACAP, PIK3C2G, PIK3CA, PIK3CD, PIK3R1, PTPN11, RPS6KA3, SH2B, SHC1, SRC, TERF2IP, TH, TUBA3 42 BRAF(183), CREBBP(1), JUN(1), MAP1B(2), MAPK10(1), MAPK8IP2(1), PIK3C2G(1), PIK3CA(3), PIK3R1(1), SHC1(1), SRC(1), TERF2IP(1) 24780522 197 186 16 4 3 3 1 187 3 0 2.22e-12 2.55e-15 1.57e-13

Table 7.  Get Full Table A Ranked List of Significantly Mutated Genesets (Excluding Significantly Mutated Genes). Number of significant genesets found: 0. Number of genesets displayed: 10

rank geneset description genes N_genes mut_tally N n npat nsite nsil n1 n2 n3 n4 n5 n6 p_ns_s p q
1 ATMPATHWAY The tumor-suppressing protein kinase ATM responds to radiation-induced DNA damage by blocking cell-cycle progression and activating DNA repair. ABL1, ATM, BRCA1, CDKN1A, CHEK1, CHEK2, GADD45A, JUN, MAPK8, MDM2, MRE11A, NBS1, NFKB1, NFKBIA, RAD50, RAD51, RBBP8, RELA, TP53, TP73 19 ABL1(1), ATM(5), BRCA1(1), CHEK1(1), CHEK2(2), JUN(1), RAD51(1), RBBP8(1), TP53(3), TP73(3) 14326099 19 18 19 0 1 6 2 3 7 0 0.0071 0.00038 0.24
2 PLK3PATHWAY Active Plk3 phosphorylates CDC25c, blocking the G2/M transition, and phosphorylates p53 to induce apoptosis. ATM, ATR, CDC25C, CHEK1, CHEK2, CNK, TP53, YWHAH 7 ATM(5), ATR(1), CHEK1(1), CHEK2(2), TP53(3) 7677248 12 12 12 1 0 1 1 3 7 0 0.27 0.00098 0.3
3 ARFPATHWAY Cyclin-dependent kinase inhibitor 2A is a tumor suppressor that induces G1 arrest and can activate the p53 pathway, leading to G2/M arrest. ABL1, CDKN2A, E2F1, MDM2, MYC, PIK3CA, PIK3R1, POLR1A, POLR1B, POLR1C, POLR1D, RAC1, RB1, TBX2, TP53, TWIST1 16 ABL1(1), MYC(1), PIK3CA(3), PIK3R1(1), POLR1A(1), POLR1B(2), TP53(3), TWIST1(1) 9760763 13 13 13 0 1 2 1 2 7 0 0.032 0.003 0.6
4 TERTPATHWAY hTERC, the RNA subunit of telomerase, and hTERT, the catalytic protein subunit, are required for telomerase activity and are overexpressed in many cancers. HDAC1, MAX, MYC, SP1, SP3, TP53, WT1, ZNF42 7 MYC(1), SP1(1), TP53(3), WT1(1) 3398513 6 6 6 0 0 0 2 1 3 0 0.16 0.0088 0.96
5 HSA00760_NICOTINATE_AND_NICOTINAMIDE_METABOLISM Genes involved in nicotinate and nicotinamide metabolism AOX1, BST1, C9orf95, CD38, ENPP1, ENPP3, NADK, NADSYN1, NMNAT1, NMNAT2, NMNAT3, NNMT, NNT, NP, NT5C, NT5C1A, NT5C1B, NT5C2, NT5C3, NT5E, NT5M, NUDT12, PBEF1, QPRT 22 AOX1(1), C9orf95(1), CD38(1), ENPP1(2), NADK(1), NADSYN1(1), NNT(1), NT5C3(1), NT5E(1), NUDT12(1), QPRT(1) 10362895 12 11 12 1 4 2 4 1 1 0 0.069 0.01 0.96
6 METHIONINE_METABOLISM AHCY, BHMT, CBS, CTH, DNMT1, DNMT2, DNMT3A, DNMT3B, MARS, MARS2, MAT1A, MAT2B, MTR 12 DNMT1(1), DNMT3A(5), MARS(1), MARS2(1), MAT1A(1), MTR(2) 8369673 11 10 11 0 3 1 0 2 5 0 0.047 0.012 0.96
7 CTLA4PATHWAY T cell activation requires interaction with an antigen-MHC-I complex on an antigen-presenting cell (APC), as well as CD28 interaction with the APC's CD80 or 86. CD28, CD3D, CD3E, CD3G, CD3Z, CD80, CD86, CTLA4, GRB2, HLA-DRA, HLA-DRB1, ICOS, ICOSL, IL2, ITK, LCK, PIK3CA, PIK3R1, PTPN11, TRA@, TRB@ 17 CD28(1), CD3D(1), HLA-DRA(1), LCK(1), PIK3CA(3), PIK3R1(1) 6150701 8 8 8 0 2 1 2 2 1 0 0.12 0.012 0.96
8 HSA00271_METHIONINE_METABOLISM Genes involved in methionine metabolism AHCY, AMD1, BHMT, CBS, CTH, DNMT1, DNMT3A, DNMT3B, KIAA0828, MARS, MARS2, MAT1A, MAT2B, MTAP, MTFMT, MTR, SRM, TAT 17 DNMT1(1), DNMT3A(5), MARS(1), MARS2(1), MAT1A(1), MTR(2), TAT(1) 9989059 12 11 12 0 3 1 0 2 6 0 0.048 0.015 0.96
9 TCRAPATHWAY The kinases Lck and Fyn phosphorylate and activate the T cell receptor, which recognizes antigen-bound MHCII and leads to T cell activation. CD3D, CD3E, CD3G, CD3Z, CD4, FYN, HLA-DRA, HLA-DRB1, LCK, PTPRC, TRA@, TRB@, ZAP70 10 CD3D(1), CD4(1), FYN(1), HLA-DRA(1), LCK(1), PTPRC(1) 4309898 6 6 6 0 4 0 1 0 1 0 0.15 0.017 0.96
10 BBCELLPATHWAY Fas ligand expression by T cells induces apoptosis in Fas-expressing, inactive B cells. CD28, CD4, HLA-DRA, HLA-DRB1, TNFRSF5, TNFRSF6, TNFSF5, TNFSF6 4 CD28(1), CD4(1), HLA-DRA(1) 1139847 3 3 3 0 2 0 1 0 0 0 0.36 0.018 0.96
Methods & Data
Methods

In brief, we tabulate the number of mutations and the number of covered bases for each gene. The counts are broken down by mutation context category: four context categories that are discovered by MutSig, and one for indel and 'null' mutations, which include indels, nonsense mutations, splice-site mutations, and non-stop (read-through) mutations. For each gene, we calculate the probability of seeing the observed constellation of mutations, i.e. the product P1 x P2 x ... x Pm, or a more extreme one, given the background mutation rates calculated across the dataset. [1]

Download Results

This is an experimental feature. The full results of the analysis summarized in this report can be downloaded from the TCGA Data Coordination Center.

References
[1] TCGA, Integrated genomic analyses of ovarian carcinoma, Nature 474:609 - 615 (2011)
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