Thyroid Adenocarcinoma: Mutation Analysis (MutSig v2.0)
Maintained by Dan DiCara (Broad Institute)
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

  • 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.final_analysis_set.maf

  • Significantly mutated genes (q ≤ 0.1): 41

  • Mutations seen in COSMIC: 249

  • Significantly mutated genes in COSMIC territory: 11

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

  • Significantly mutated genesets: 77

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

Mutation Preprocessing

  • Read 323 MAFs of type "Broad"

  • Total number of mutations in input MAFs: 11439

  • After removing 99 mutations outside chr1-24: 11340

  • After removing 1339 blacklisted mutations: 10001

  • After removing 3104 noncoding mutations: 6897

  • After collapsing adjacent/redundant mutations: 6895

Mutation Filtering

  • Number of mutations before filtering: 6895

  • After removing 289 mutations outside gene set: 6606

  • After removing 2 mutations outside category set: 6604

Results
Breakdown of Mutations by Type

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

type count
Frame_Shift_Del 317
Frame_Shift_Ins 112
In_Frame_Del 117
In_Frame_Ins 18
Missense_Mutation 4143
Nonsense_Mutation 194
Nonstop_Mutation 4
Silent 1572
Splice_Site 120
Translation_Start_Site 7
Total 6604
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 2.8 2.1
*Cp(A/C/T)->T 980 4313476957 2.3e-07 0.23 0.43 1.7
A->G 826 4649186676 1.8e-07 0.18 0.34 2.3
transver 1558 9489374871 1.6e-07 0.16 0.31 5
indel+null 884 9489374871 9.3e-08 0.093 0.18 NaN
double_null 2 9489374871 2.1e-10 0.00021 0.0004 NaN
Total 5032 9489374871 5.3e-07 0.53 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.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_ks = p-value for clustering of mutations (Kolmogorov-Smirnoff test)

  • 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: 41. 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_ks 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 2e-07 2e-07 0 <1.00e-15 <4.52e-12
2 NRAS neuroblastoma RAS viral (v-ras) oncogene homolog 189273 26 26 2 0 0 0 20 6 0 0 5.22e-15 0.00016 2e-07 0.0002 0 <1.00e-15 <4.52e-12
3 HRAS v-Ha-ras Harvey rat sarcoma viral oncogene homolog 209181 12 12 2 0 0 0 9 3 0 0 1.52e-14 0.13 2e-07 0.000079 0 <1.00e-15 <4.52e-12
4 ACRC acidic repeat containing 609349 4 2 2 0 0 2 0 2 0 0 0.00945 0.37 2e-07 0.72 0 <1.00e-15 <4.52e-12
5 EMG1 EMG1 nucleolar protein homolog (S. cerevisiae) 220090 6 6 2 0 0 0 0 0 6 0 3.82e-10 1 2e-07 0.89 9.8e-06 1.28e-13 4.64e-10
6 RPTN repetin 763230 8 8 6 0 0 0 1 0 7 0 2.46e-09 0.65 0.00082 0.12 0.00065 4.53e-11 1.37e-07
7 EIF1AX eukaryotic translation initiation factor 1A, X-linked 142447 5 5 4 0 0 4 0 1 0 0 6.88e-10 0.27 0.014 0.014 0.0051 9.68e-11 2.50e-07
8 ZNF845 zinc finger protein 845 928346 6 6 3 0 0 3 3 0 0 0 3.35e-06 0.09 2e-06 1 0.000015 1.24e-09 2.81e-06
9 IL32 interleukin 32 168065 3 3 1 0 0 0 0 0 3 0 1.64e-05 1 2.6e-06 0.91 6.8e-06 2.66e-09 5.35e-06
10 CCDC15 coiled-coil domain containing 15 671425 5 5 1 1 0 0 0 5 0 0 1.93e-05 0.72 2e-07 1 0.000017 7.40e-09 1.34e-05
11 TMEM90B 254847 3 3 1 0 0 0 0 0 3 0 0.000228 1 2e-06 0.85 1.6e-06 8.31e-09 1.37e-05
12 TG thyroglobulin 2717568 16 16 16 3 1 0 1 4 10 0 3.11e-09 0.82 0.1 0.46 0.19 1.29e-08 1.95e-05
13 ZNF878 zinc finger protein 878 523994 4 4 2 0 0 0 0 4 0 0 9.45e-05 0.54 2e-07 1 0.000012 2.45e-08 3.41e-05
14 SYNPO2L synaptopodin 2-like 692797 3 3 1 0 0 0 3 0 0 0 0.00171 0.27 2.6e-06 0.0018 1.4e-06 4.98e-08 6.44e-05
15 ZNF479 zinc finger protein 479 507416 3 3 1 0 0 0 0 3 0 0 0.00167 0.65 4e-07 1 1.8e-06 6.19e-08 7.46e-05
16 MUC7 mucin 7, secreted 368847 5 5 5 1 0 2 2 0 1 0 3.82e-07 0.41 0.3 0.08 0.14 9.62e-07 0.00109
17 PPM1D protein phosphatase 1D magnesium-dependent, delta isoform 502843 5 5 5 0 0 1 0 0 4 0 2.08e-06 0.7 0.026 0.78 0.064 2.25e-06 0.00239
18 ZNF799 zinc finger protein 799 607484 5 5 2 1 0 0 5 0 0 0 6.50e-06 0.26 0.011 0.98 0.029 3.11e-06 0.00312
19 ATAD2 ATPase family, AAA domain containing 2 1353048 4 4 3 0 0 1 1 0 2 0 0.00324 0.45 0.00016 0.17 0.0002 9.79e-06 0.00932
20 SF3B2 splicing factor 3b, subunit 2, 145kDa 883027 2 2 1 0 0 0 0 0 2 0 0.0587 1 0.00036 0.0049 0.000014 1.27e-05 0.0115
21 TROAP trophinin associated protein (tastin) 787729 5 3 3 0 0 1 2 2 0 0 0.00655 0.17 0.000015 1 0.00016 1.58e-05 0.0136
22 SLC26A11 solute carrier family 26, member 11 571218 3 3 2 0 0 0 0 2 1 0 0.00420 0.62 8e-05 0.78 0.00031 1.88e-05 0.0154
23 MAP3K3 mitogen-activated protein kinase kinase kinase 3 653710 4 4 4 0 0 2 0 1 1 0 0.000190 0.28 0.0036 0.23 0.0087 2.37e-05 0.0187
24 PRG4 proteoglycan 4 1374896 7 4 7 1 0 1 1 2 3 0 0.00317 0.55 0.00018 0.99 0.00074 3.27e-05 0.0245
25 KRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog 224332 3 3 3 0 0 0 1 2 0 0 0.000119 0.48 0.12 0.01 0.02 3.39e-05 0.0245
26 CHEK2 CHK2 checkpoint homolog (S. pombe) 515569 2 2 2 0 0 0 0 1 1 0 0.0205 0.71 0.00013 0.77 0.00013 3.80e-05 0.0264
27 KIAA0182 KIAA0182 1037502 2 2 1 0 0 0 0 0 2 0 0.0583 1 0.00028 0.081 0.000085 6.55e-05 0.0428
28 LMX1B LIM homeobox transcription factor 1, beta 315824 2 2 1 0 0 0 0 0 2 0 0.00366 1 0.00078 0.031 0.0014 6.63e-05 0.0428
29 GLI2 GLI-Kruppel family member GLI2 1335844 3 3 3 0 2 0 0 0 1 0 0.0183 0.36 0.48 0.00024 0.00032 7.64e-05 0.0463
30 POU4F2 POU class 4 homeobox 2 346504 2 2 1 0 0 0 0 0 2 0 0.00753 1 0.00082 0.98 0.00082 8.02e-05 0.0463
31 ZNF704 zinc finger protein 704 396074 2 2 1 0 0 0 0 0 2 0 0.00803 1 0.00078 0.73 0.00078 8.15e-05 0.0463
32 TYSND1 trypsin domain containing 1 238129 2 2 1 0 0 0 0 0 2 0 0.00274 1 0.00056 0.91 0.0023 8.18e-05 0.0463
33 DPYS dihydropyrimidinase 428837 2 2 1 0 0 0 0 0 2 0 0.0104 1 0.00064 0.82 0.00064 8.61e-05 0.0472
34 NLRP6 NLR family, pyrin domain containing 6 591829 2 2 1 0 0 0 2 0 0 0 0.00802 0.69 0.0013 0.001 0.00092 9.41e-05 0.0501
35 POTEE POTE ankyrin domain family, member E 694920 2 2 1 1 0 0 2 0 0 0 0.0102 0.79 0.00086 0.81 0.00086 0.000111 0.0575
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.

ACRC

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

EMG1

Figure S5.  This figure depicts the distribution of mutations and mutation types across the EMG1 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.

ZNF845

Figure S8.  This figure depicts the distribution of mutations and mutation types across the ZNF845 significant gene.

IL32

Figure S9.  This figure depicts the distribution of mutations and mutation types across the IL32 significant gene.

CCDC15

Figure S10.  This figure depicts the distribution of mutations and mutation types across the CCDC15 significant gene.

TG

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

ZNF878

Figure S12.  This figure depicts the distribution of mutations and mutation types across the ZNF878 significant gene.

SYNPO2L

Figure S13.  This figure depicts the distribution of mutations and mutation types across the SYNPO2L significant gene.

ZNF479

Figure S14.  This figure depicts the distribution of mutations and mutation types across the ZNF479 significant gene.

MUC7

Figure S15.  This figure depicts the distribution of mutations and mutation types across the MUC7 significant gene.

PPM1D

Figure S16.  This figure depicts the distribution of mutations and mutation types across the PPM1D significant gene.

ZNF799

Figure S17.  This figure depicts the distribution of mutations and mutation types across the ZNF799 significant gene.

ATAD2

Figure S18.  This figure depicts the distribution of mutations and mutation types across the ATAD2 significant gene.

SF3B2

Figure S19.  This figure depicts the distribution of mutations and mutation types across the SF3B2 significant gene.

TROAP

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

SLC26A11

Figure S21.  This figure depicts the distribution of mutations and mutation types across the SLC26A11 significant gene.

MAP3K3

Figure S22.  This figure depicts the distribution of mutations and mutation types across the MAP3K3 significant gene.

PRG4

Figure S23.  This figure depicts the distribution of mutations and mutation types across the PRG4 significant gene.

KRAS

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

CHEK2

Figure S25.  This figure depicts the distribution of mutations and mutation types across the CHEK2 significant gene.

KIAA0182

Figure S26.  This figure depicts the distribution of mutations and mutation types across the KIAA0182 significant gene.

LMX1B

Figure S27.  This figure depicts the distribution of mutations and mutation types across the LMX1B significant gene.

GLI2

Figure S28.  This figure depicts the distribution of mutations and mutation types across the GLI2 significant gene.

POU4F2

Figure S29.  This figure depicts the distribution of mutations and mutation types across the POU4F2 significant gene.

ZNF704

Figure S30.  This figure depicts the distribution of mutations and mutation types across the ZNF704 significant gene.

TYSND1

Figure S31.  This figure depicts the distribution of mutations and mutation types across the TYSND1 significant gene.

DPYS

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

NLRP6

Figure S33.  This figure depicts the distribution of mutations and mutation types across the NLRP6 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 BRAF v-raf murine sarcoma viral oncogene homolog B1 183 88 183 28424 1922790 0 0
2 NRAS neuroblastoma RAS viral (v-ras) oncogene homolog 26 28 26 9044 33748 0 0
3 HRAS v-Ha-ras Harvey rat sarcoma viral oncogene homolog 12 19 12 6137 2496 0 0
4 KRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog 3 51 3 16473 14910 1.1e-07 0.00012
5 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 3 184 3 59432 51 5.1e-06 0.0046
6 C4BPA complement component 4 binding protein, alpha 1 1 1 323 1 0.00017 0.07
7 PCGF2 polycomb group ring finger 2 2 1 1 323 1 0.00017 0.07
8 SEZ6L seizure related 6 homolog (mouse)-like 2 1 1 323 1 0.00017 0.07
9 SMC3 structural maintenance of chromosomes 3 1 1 1 323 1 0.00017 0.07
10 TNFRSF9 tumor necrosis factor receptor superfamily, member 9 1 1 1 323 1 0.00017 0.07

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
345 BRAF v-raf murine sarcoma viral oncogene homolog B1 183 0 16471 16653 16653 16471 16653 16653
2147 NRAS neuroblastoma RAS viral (v-ras) oncogene homolog 26 0 325 325 325 325 325 325
1440 HRAS v-Ha-ras Harvey rat sarcoma viral oncogene homolog 12 0 66 66 66 66 66 66
529 CCDC15 coiled-coil domain containing 15 5 0 10 10 10 10 10 10
3687 ZNF799 zinc finger protein 799 5 0 6 6 6 6 6 6
3696 ZNF845 zinc finger protein 845 6 0 6 6 6 6 6 6
991 EIF1AX eukaryotic translation initiation factor 1A, X-linked 4 0 3 6 6 3 6 6
1098 FAM47C family with sequence similarity 47, member C 5 0 3 3 3 3 3 3
3095 SYNPO2L synaptopodin 2-like 3 0 3 3 3 3 3 3
3622 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: 77. 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 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 <1.00e-15 <9.57e-14
2 HSA04510_FOCAL_ADHESION Genes involved in focal adhesion ACTB, ACTG1, ACTN1, ACTN2, ACTN3, ACTN4, AKT1, AKT2, AKT3, ARHGAP5, BAD, BCAR1, BCL2, BIRC2, BIRC3, BIRC4, BRAF, CAPN2, CAV1, CAV2, CAV3, CCND1, CCND2, CCND3, CDC42, CHAD, COL11A1, COL11A2, COL1A1, COL1A2, COL2A1, COL3A1, COL4A1, COL4A2, COL4A4, COL4A6, COL5A1, COL5A2, COL5A3, COL6A1, COL6A2, COL6A3, COL6A6, COMP, CRK, CRKL, CTNNB1, DIAPH1, DOCK1, EGF, EGFR, ELK1, ERBB2, FARP2, FIGF, FLNA, FLNB, FLNC, FLT1, FN1, FYN, GRB2, GRLF1, GSK3B, HGF, HRAS, IBSP, IGF1, IGF1R, ILK, ITGA1, ITGA10, ITGA11, ITGA2, ITGA2B, ITGA3, ITGA4, ITGA5, ITGA6, ITGA7, ITGA8, ITGA9, ITGAV, ITGB1, ITGB3, ITGB4, ITGB5, ITGB6, ITGB7, ITGB8, JUN, KDR, LAMA1, LAMA2, LAMA3, LAMA4, LAMA5, LAMB1, LAMB2, LAMB3, LAMB4, LAMC1, LAMC2, LAMC3, LOC653852, MAP2K1, MAPK1, MAPK10, MAPK3, MAPK8, MAPK9, MET, MLCK, MRCL3, MRLC2, MYL2, MYL5, MYL7, MYL8P, MYL9, MYLC2PL, MYLK, MYLK2, MYLPF, PAK1, PAK2, PAK3, PAK4, PAK6, PAK7, PARVA, PARVB, PARVG, PDGFA, PDGFB, PDGFC, PDGFD, PDGFRA, PDGFRB, PDPK1, PGF, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PIP5K1C, PPP1CA, PPP1CB, PPP1CC, PPP1R12A, PRKCA, PRKCB1, PRKCG, PTEN, PTK2, PXN, RAC1, RAC2, RAC3, RAF1, RAP1A, RAP1B, RAPGEF1, RELN, RHOA, ROCK1, ROCK2, SHC1, SHC2, SHC3, SHC4, SOS1, SOS2, SPP1, SRC, THBS1, THBS2, THBS3, THBS4, TLN1, TLN2, TNC, TNN, TNR, TNXB, VASP, VAV1, VAV2, VAV3, VCL, VEGFA, VEGFB, VEGFC, VTN, VWF, ZYX 192 ACTB(1), BRAF(183), CDC42(1), COL11A1(2), COL11A2(1), COL1A1(1), COL2A1(1), COL3A1(1), COL4A1(3), COL4A2(2), COL4A4(3), COL4A6(1), COL5A1(3), COL5A2(1), COL5A3(6), COL6A2(3), COL6A3(2), COL6A6(1), CTNNB1(2), ERBB2(1), FIGF(1), FLNA(1), FLNC(3), FN1(1), FYN(1), HRAS(12), IGF1R(1), ITGA10(1), ITGA3(2), ITGA8(1), ITGB1(2), ITGB3(1), ITGB4(1), ITGB8(1), JUN(1), KDR(1), LAMA2(1), LAMA3(2), LAMA4(3), LAMA5(1), LAMB1(1), LAMB2(1), LAMB4(1), LAMC1(2), LAMC2(1), LAMC3(1), MAPK10(1), MYLK(2), PAK3(1), PAK7(1), PDGFRB(1), PIK3CA(3), PIK3CB(1), PIK3CG(1), PIK3R1(1), PIK3R5(3), PTEN(2), RAPGEF1(1), RELN(1), SHC1(1), SOS1(1), SRC(1), THBS1(1), THBS2(1), THBS3(1), THBS4(1), TLN1(1), TLN2(2), TNC(1), TNN(1), TNR(3), TNXB(1), VAV2(1), VCL(1), VEGFA(1), VTN(1), VWF(1) 178619783 304 226 112 35 18 22 21 221 21 1 1.76e-07 <1.00e-15 <9.57e-14
3 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) 28143487 195 188 14 3 6 2 1 186 0 0 1.17e-12 <1.00e-15 <9.57e-14
4 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) 24780522 196 185 15 4 3 3 1 187 2 0 2.22e-12 <1.00e-15 <9.57e-14
5 ST_ERK1_ERK2_MAPK_PATHWAY The Erk1 and Erk2 MAP kinase pathways are regulated by Raf, Mos, and Tpl-2. ARAF1, ATF1, BAD, BRAF, COPEB, CREB1, CREB3, CREB5, DUSP4, DUSP6, DUSP9, EEF2K, EIF4E, GRB2, HTATIP, MAP2K1, MAP2K2, MAP3K8, MAPK1, MAPK3, MKNK1, MKNK2, MOS, NFKB1, RAP1A, RPS6KA1, RPS6KA2, RPS6KA3, SHC1, SOS1, SOS2, TRAF3 29 BRAF(183), EEF2K(1), MAP3K8(1), MKNK2(1), RPS6KA1(1), SHC1(1), SOS1(1) 14219870 189 184 8 3 2 2 1 183 1 0 3.38e-12 <1.00e-15 <9.57e-14
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 1.11e-15 9.57e-14
7 MAPKPATHWAY The mitogen-activated protein (MAP) kinase pathway is a common signaling mechanism and has four main sub-pathways: Erk, JNK/SAPK, p53, and ERK5. ARAF1, ATF2, BRAF, CEBPA, CHUK, CREB1, DAXX, ELK1, FOS, GRB2, HRAS, IKBKB, JUN, MAP2K1, MAP2K2, MAP2K3, MAP2K4, MAP2K5, MAP2K6, MAP2K7, MAP3K1, MAP3K10, MAP3K11, MAP3K12, MAP3K13, MAP3K14, MAP3K2, MAP3K3, MAP3K4, MAP3K5, MAP3K6, MAP3K7, MAP3K8, MAP3K9, MAP4K1, MAP4K2, MAP4K3, MAP4K4, MAP4K5, MAPK1, MAPK10, MAPK11, MAPK12, MAPK13, MAPK14, MAPK3, MAPK4, MAPK6, MAPK7, MAPK8, MAPK9, MAPKAPK2, MAPKAPK3, MAPKAPK5, MAX, MEF2A, MEF2B, MEF2C, MEF2D, MKNK1, MKNK2, MYC, NFKB1, NFKBIA, PAK1, PAK2, PDZGEF1, RAC1, RAF1, RELA, RIPK1, RPS6KA1, RPS6KA2, RPS6KA3, RPS6KA4, RPS6KA5, RPS6KB1, RPS6KB2, SHC1, SP1, STAT1, TGFB1, TGFB2, TGFB3, TGFBR1, TRADD, TRAF2 84 BRAF(183), HRAS(12), JUN(1), MAP2K5(1), MAP2K6(1), MAP3K1(1), MAP3K3(4), MAP3K6(1), MAP3K8(1), MAP4K4(1), MAPK10(1), MAPK4(1), MAPKAPK3(1), MEF2B(1), MKNK2(1), MYC(1), RPS6KA1(1), RPS6KB2(1), SHC1(1), SP1(1), STAT1(1), TGFB1(1) 45848909 218 202 27 4 6 4 12 192 4 0 1.13e-14 1.33e-15 9.57e-14
8 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 1.44e-15 9.57e-14
9 ST_INTEGRIN_SIGNALING_PATHWAY Integrins are transmembrane receptors that mediate cell growth, survival, and migration by binding to ligands in the extracellular matrix. ABL1, ACK1, ACTN1, ACTR2, ACTR3, AKT1, AKT2, AKT3, ANGPTL2, ARHGEF6, ARHGEF7, BCAR1, BRAF, CAV1, CDC42, CDKN2A, CRK, CSE1L, DDEF1, DOCK1, EPHB2, FYN, GRAF, GRB2, GRB7, GRF2, GRLF1, ILK, ITGA1, ITGA10, ITGA11, ITGA2, ITGA3, ITGA4, ITGA5, ITGA6, ITGA7, ITGA8, ITGA9, ITGB3BP, MAP2K4, MAP2K7, MAP3K11, MAPK1, MAPK10, MAPK8, MAPK8IP1, MAPK8IP2, MAPK8IP3, MAPK9, MRAS, MYLK, MYLK2, P4HB, PAK1, PAK2, PAK3, PAK4, PAK6, PAK7, PIK3CA, PIK3CB, PKLR, PLCG1, PLCG2, PTEN, PTK2, RAF1, RALA, RHO, ROCK1, ROCK2, SHC1, SOS1, SOS2, SRC, TERF2IP, TLN1, TLN2, VASP, WAS, ZYX 78 ABL1(1), ANGPTL2(1), ARHGEF6(1), ARHGEF7(2), BRAF(183), CDC42(1), FYN(1), GRB7(1), ITGA10(1), ITGA3(2), ITGA8(1), MAPK10(1), MAPK8IP2(1), MYLK(2), PAK3(1), PAK7(1), PIK3CA(3), PIK3CB(1), PLCG2(1), PTEN(2), SHC1(1), SOS1(1), SRC(1), TLN1(1), TLN2(2) 58950476 214 193 33 13 9 5 2 194 3 1 2.79e-08 1.55e-15 9.57e-14
10 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) 5335473 186 183 5 2 0 0 1 183 2 0 2.63e-12 1.55e-15 9.57e-14

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 18 ABL1(1), ATM(5), BRCA1(1), CHEK1(1), JUN(1), RAD51(1), RBBP8(1), TP53(3), TP73(3) 13810530 17 16 17 0 1 6 2 2 6 0 0.0098 0.001 0.63
2 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 0.0021 0.65
3 PLK3PATHWAY Active Plk3 phosphorylates CDC25c, blocking the G2/M transition, and phosphorylates p53 to induce apoptosis. ATM, ATR, CDC25C, CHEK1, CHEK2, CNK, TP53, YWHAH 6 ATM(5), ATR(1), CHEK1(1), TP53(3) 7161679 10 10 10 1 0 1 1 2 6 0 0.34 0.0037 0.76
4 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 0.0074 0.82
5 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 0.0075 0.82
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(1) 8369673 10 10 10 0 3 1 0 2 4 0 0.047 0.0087 0.82
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 0.01 0.82
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(1), TAT(1) 9989059 11 11 11 0 3 1 0 2 5 0 0.048 0.011 0.82
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 0.015 0.88
10 P53PATHWAY p53 induces cell cycle arrest or apoptosis under conditions of DNA damage. APAF1, ATM, BAX, BCL2, CCND1, CCNE1, CDK2, CDK4, CDKN1A, E2F1, GADD45A, MDM2, PCNA, RB1, TIMP3, TP53 16 APAF1(2), ATM(5), TP53(3) 8702713 10 10 10 0 0 1 1 2 6 0 0.14 0.015 0.88
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)
Copyright © 2012 Broad Institute TCGA GDAC as part of the TCGA Research Network. All rights reserved.
Made with Nozzle