Mutation Analysis (MutSig v2.0)
Thyroid Adenocarcinoma (Mut_RAS)
14 July 2013  |  awg_thca__2013_07_14
Maintainer Information
Citation Information
doi:10.7908/C1CJ8C0K
Maintained by Dan DiCara (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2013): Mutation Analysis (MutSig v2.0). Broad Institute of MIT and Harvard. doi:10.7908/C1CJ8C0K
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-Mut_RAS

  • Number of patients in set: 52

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-Mut_RAS.final_analysis_set.maf

  • Significantly mutated genes (q ≤ 0.1): 4

  • Mutations seen in COSMIC: 53

  • Significantly mutated genes in COSMIC territory: 3

  • Genes with clustered mutations (≤ 3 aa apart): 5

  • Significantly mutated genesets: 80

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

Mutation Preprocessing

  • Read 52 MAFs of type "Broad"

  • Total number of mutations in input MAFs: 924

  • After removing 7 noncoding mutations: 917

  • After collapsing adjacent/redundant mutations: 868

Mutation Filtering

  • Number of mutations before filtering: 868

  • After removing 37 mutations outside gene set: 831

Results
Breakdown of Mutations by Type

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

type count
Frame_Shift_Del 27
Frame_Shift_Ins 3
In_Frame_Del 4
Missense_Mutation 543
Nonsense_Mutation 34
Nonstop_Mutation 1
Silent 189
Splice_Site 30
Total 831
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 121 84478677 1.4e-06 1.4 3.4 2.1
*Cp(A/C/T)->T 90 691246206 1.3e-07 0.13 0.31 1.7
A->G 145 744150021 1.9e-07 0.19 0.46 2.3
transver 187 1519874904 1.2e-07 0.12 0.29 5
indel+null 99 1519874904 6.5e-08 0.065 0.15 NaN
double_null 0 1519874904 0 0 0 NaN
Total 642 1519874904 4.2e-07 0.42 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-Mut_RAS.patients.counts_and_rates.txt

Lego Plots

The mutation spectrum is depicted in the lego plots below in which the 96 possible mutation types are subdivided into six large blocks, color-coded to reflect the base substitution type. Each large block is further subdivided into the 16 possible pairs of 5' and 3' neighbors, as listed in the 4x4 trinucleotide context legend. The height of each block corresponds to the mutation frequency for that kind of mutation (counts of mutations normalized by the base coverage in a given bin). The shape of the spectrum is a signature for dominant mutational mechanisms in different tumor types.

Figure 3.  Get High-res Image SNV Mutation rate lego plot for entire set. Each bin is normalized by base coverage for that bin. Colors represent the six SNV types on the upper right. The three-base context for each mutation is labeled in the 4x4 legend on the lower right. The fractional breakdown of SNV counts is shown in the pie chart on the upper left. If this figure is blank, not enough information was provided in the MAF to generate it.

Figure 4.  Get High-res Image SNV Mutation rate lego plots for 4 slices of mutation allele fraction (0<=AF<0.1, 0.1<=AF<0.25, 0.25<=AF<0.5, & 0.5<=AF) . The color code and three-base context legends are the same as the previous figure. If this figure is blank, not enough information was provided in the MAF to generate it.

CoMut Plot

Figure 5.  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: 4. 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_clust p_cons p_joint p q
1 NRAS neuroblastoma RAS viral (v-ras) oncogene homolog 30461 34 34 2 0 0 0 27 7 0 0 3.4e-15 8.8e-06 0 0.00022 0 <1.00e-15 <9.04e-12
2 HRAS v-Ha-ras Harvey rat sarcoma viral oncogene homolog 33709 14 14 2 0 0 0 11 3 0 0 4.2e-15 0.094 0 0.00014 0 <1.00e-15 <9.04e-12
3 KRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog 35034 4 4 3 0 0 0 1 3 0 0 9.6e-10 0.41 0.037 0.003 0.0023 6.23e-11 3.75e-07
4 CHEK2 CHK2 checkpoint homolog (S. pombe) 81086 3 3 3 0 0 0 0 2 1 0 4.3e-06 0.6 0.044 0.67 0.13 8.80e-06 0.0398
5 EFCAB1 EF-hand calcium binding domain 1 33293 1 1 1 0 1 0 0 0 0 0 0.0001 0.86 NaN NaN NaN 0.000105 0.372
6 DNAJC11 DnaJ (Hsp40) homolog, subfamily C, member 11 87491 2 2 2 0 0 0 1 1 0 0 0.00028 0.61 0.012 0.14 0.035 0.000123 0.372
7 KRTAP4-12 keratin associated protein 4-12 30663 1 1 1 0 1 0 0 0 0 0 0.00023 1 NaN NaN NaN 0.000230 0.501
8 UNC50 unc-50 homolog (C. elegans) 40497 1 1 1 0 1 0 0 0 0 0 0.00028 0.72 NaN NaN NaN 0.000278 0.501
9 FAM131C family with sequence similarity 131, member C 27503 1 1 1 0 0 0 0 0 1 0 0.00028 0.58 NaN NaN NaN 0.000280 0.501
10 TG thyroglobulin 435860 3 3 3 1 0 0 1 1 1 0 0.000094 0.81 0.17 0.97 0.3 0.000320 0.501
11 RBM7 RNA binding motif protein 7 42503 1 1 1 0 1 0 0 0 0 0 0.00032 0.71 NaN NaN NaN 0.000324 0.501
12 EEF1A1 eukaryotic translation elongation factor 1 alpha 1 69958 2 2 2 0 0 0 1 0 1 0 0.000052 0.67 0.38 0.99 0.56 0.000332 0.501
13 PCDHGC5 protocadherin gamma subfamily C, 5 150148 2 2 2 1 0 0 1 1 0 0 0.00037 0.79 NaN NaN NaN 0.000373 0.519
14 HOXA1 homeobox A1 52824 1 1 1 0 0 0 1 0 0 0 0.00049 0.78 NaN NaN NaN 0.000489 0.632
15 SLA Src-like-adaptor 42997 2 2 2 0 0 0 1 0 1 0 0.000058 0.76 0.69 0.9 1 0.000628 0.721
16 OR5T2 olfactory receptor, family 5, subfamily T, member 2 55921 1 1 1 0 1 0 0 0 0 0 0.00064 0.64 NaN NaN NaN 0.000638 0.721
17 GIP gastric inhibitory polypeptide 22398 1 1 1 0 0 1 0 0 0 0 0.00073 0.55 NaN NaN NaN 0.000733 0.779
18 CACNA2D1 calcium channel, voltage-dependent, alpha 2/delta subunit 1 159056 2 2 2 0 0 0 0 1 1 0 0.00069 0.85 0.098 0.13 0.12 0.000862 0.805
19 GRAMD2 GRAM domain containing 2 55493 2 2 2 0 0 0 1 1 0 0 0.00015 0.63 0.65 0.21 0.55 0.000872 0.805
20 NBPF14 neuroblastoma breakpoint family, member 14 80732 1 1 1 0 0 0 0 0 1 0 0.00096 1 NaN NaN NaN 0.000963 0.805
21 XPNPEP1 X-prolyl aminopeptidase (aminopeptidase P) 1, soluble 100645 1 1 1 0 1 0 0 0 0 0 0.00097 0.67 NaN NaN NaN 0.000970 0.805
22 SH2D6 SH2 domain containing 6 21841 1 1 1 0 0 1 0 0 0 0 0.00098 0.6 NaN NaN NaN 0.000980 0.805
23 KRTAP8-1 keratin associated protein 8-1 10119 1 1 1 0 0 1 0 0 0 0 0.001 0.62 NaN NaN NaN 0.00102 0.805
24 DEFB119 defensin, beta 119 26877 1 1 1 0 1 0 0 0 0 0 0.0011 0.9 NaN NaN NaN 0.00110 0.830
25 MPV17L MPV17 mitochondrial membrane protein-like 13553 1 1 1 0 0 0 0 0 1 0 0.0013 1 NaN NaN NaN 0.00126 0.876
26 KIR3DL2 killer cell immunoglobulin-like receptor, three domains, long cytoplasmic tail, 2 45653 1 1 1 0 1 0 0 0 0 0 0.0014 0.67 NaN NaN NaN 0.00141 0.876
27 B3GNT3 UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 3 58398 1 1 1 0 0 0 0 1 0 0 0.0015 0.81 NaN NaN NaN 0.00149 0.876
28 ZC3H15 zinc finger CCCH-type containing 15 61278 1 1 1 0 0 0 0 0 1 0 0.0016 1 NaN NaN NaN 0.00159 0.876
29 ASPSCR1 alveolar soft part sarcoma chromosome region, candidate 1 70268 1 1 1 1 0 0 0 0 1 0 0.0016 1 NaN NaN NaN 0.00159 0.876
30 OR4X1 olfactory receptor, family 4, subfamily X, member 1 47541 1 1 1 0 0 1 0 0 0 0 0.0016 0.55 NaN NaN NaN 0.00162 0.876
31 ERG v-ets erythroblastosis virus E26 oncogene homolog (avian) 75348 1 1 1 0 0 0 0 1 0 0 0.0016 0.84 NaN NaN NaN 0.00164 0.876
32 SUOX sulfite oxidase 85799 1 1 1 0 0 0 0 0 1 0 0.0017 1 NaN NaN NaN 0.00167 0.876
33 LRP10 low density lipoprotein receptor-related protein 10 112525 1 1 1 0 0 0 0 0 1 0 0.0017 0.61 NaN NaN NaN 0.00173 0.876
34 MED31 mediator complex subunit 31 20876 1 1 1 0 0 0 0 1 0 0 0.0018 0.88 NaN NaN NaN 0.00177 0.876
35 RAP1A RAP1A, member of RAS oncogene family 29510 1 1 1 0 0 1 0 0 0 0 0.0018 0.66 NaN NaN NaN 0.00178 0.876
NRAS

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

HRAS

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

KRAS

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

CHEK2

Figure S4.  This figure depicts the distribution of mutations and mutation types across the CHEK2 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: 3. 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 14 19 14 988 2912 3.9e-14 1.5e-10
2 NRAS neuroblastoma RAS viral (v-ras) oncogene homolog 34 33 34 1716 44132 6.8e-14 1.5e-10
3 KRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog 4 52 4 2704 15018 1.8e-13 2.7e-10
4 BRAF v-raf murine sarcoma viral oncogene homolog B1 1 89 1 4628 14374 0.002 1
5 A4GNT alpha-1,4-N-acetylglucosaminyltransferase 0 0 0 0 0 1 1
6 AACS acetoacetyl-CoA synthetase 0 0 0 0 0 1 1
7 ABCA9 ATP-binding cassette, sub-family A (ABC1), member 9 0 0 0 0 0 1 1
8 ABCC10 ATP-binding cassette, sub-family C (CFTR/MRP), member 10 0 0 0 0 0 1 1
9 ABCF2 ATP-binding cassette, sub-family F (GCN20), member 2 0 0 0 0 0 1 1
10 ABHD2 abhydrolase domain containing 2 0 0 0 0 0 1 1

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
336 NRAS neuroblastoma RAS viral (v-ras) oncogene homolog 34 0 561 561 561 561 561 561
218 HRAS v-Ha-ras Harvey rat sarcoma viral oncogene homolog 14 0 91 91 91 91 91 91
123 DGCR8 DiGeorge syndrome critical region gene 8 2 0 1 1 1 1 1 1
85 CHEK2 CHK2 checkpoint homolog (S. pombe) 3 1 0 1 1 0 1 1
140 DNAJC11 DnaJ (Hsp40) homolog, subfamily C, member 11 2 1 0 1 1 0 1 1
261 KRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog 4 49 0 0 0 0 0 0
121 DENND5B DENN/MADD domain containing 5B 2 82 0 0 0 0 0 0
112 CYB5R4 cytochrome b5 reductase 4 2 138 0 0 0 0 0 0
204 GRAMD2 GRAM domain containing 2 2 142 0 0 0 0 0 0
216 HMCN1 hemicentin 1 2 248 0 0 0 0 0 0

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: 80. 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 HSA04662_B_CELL_RECEPTOR_SIGNALING_PATHWAY Genes involved in B cell receptor signaling pathway AKT1, AKT2, AKT3, BCL10, BLNK, BTK, CARD11, CD19, CD22, CD72, CD79A, CD79B, CD81, CHP, CHUK, CR2, FCGR2B, FOS, GSK3B, HRAS, IFITM1, IKBKB, IKBKG, INPP5D, JUN, KRAS, LILRB3, LYN, MALT1, NFAT5, NFATC1, NFATC2, NFATC3, NFATC4, NFKB1, NFKB2, NFKBIA, NFKBIB, NFKBIE, NRAS, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PLCG2, PPP3CA, PPP3CB, PPP3CC, PPP3R1, PPP3R2, PRKCB1, PTPN6, RAC1, RAC2, RAC3, RASGRP3, SYK, VAV1, VAV2, VAV3 62 HRAS(14), KRAS(4), NRAS(34) 5745523 52 52 7 2 0 0 39 13 0 0 0.000021 <1.00e-15 <1.27e-13
2 HSA04720_LONG_TERM_POTENTIATION Genes involved in long-term potentiation ADCY1, ADCY8, ARAF, ATF4, BRAF, CACNA1C, CALM1, CALM2, CALM3, CALML3, CALML6, CAMK2A, CAMK2B, CAMK2D, CAMK2G, CAMK4, CHP, CREBBP, EP300, GNAQ, GRIA1, GRIA2, GRIN1, GRIN2A, GRIN2B, GRIN2C, GRIN2D, GRM1, GRM5, HRAS, ITPR1, ITPR2, ITPR3, KRAS, MAP2K1, MAP2K2, MAPK1, MAPK3, NRAS, PLCB1, PLCB2, PLCB3, PLCB4, PPP1CA, PPP1CB, PPP1CC, PPP1R12A, PPP1R1A, PPP3CA, PPP3CB, PPP3CC, PPP3R1, PPP3R2, PRKACA, PRKACB, PRKACG, PRKCA, PRKCB1, PRKCG, PRKX, PRKY, RAF1, RAP1A, RAP1B, RAPGEF3, RPS6KA1, RPS6KA2, RPS6KA3, RPS6KA6 67 BRAF(1), GRIA1(1), GRIA2(1), HRAS(14), ITPR1(1), KRAS(4), NRAS(34), PLCB3(1), RAP1A(1) 7663435 58 52 13 1 1 1 39 16 1 0 1.7e-06 <1.00e-15 <1.27e-13
3 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(1), HRAS(14), KIR3DL2(1), KRAS(4), NRAS(34), PTK2B(1) 8769852 55 52 10 1 1 1 39 14 0 0 1.2e-06 1.11e-15 1.27e-13
4 CDMACPATHWAY Cadmium 2+ promotes cell proliferation in cultured macrophages by entering the cell via calcium channels and activating the MAP kinase pathway. CUZD1, FOS, HRAS, JUN, MAP2K1, MAPK1, MAPK3, MYC, NFKB1, NFKBIA, PLCB1, PRKCA, PRKCB1, RAF1, RELA, TNF 15 HRAS(14) 1198405 14 14 2 0 0 0 11 3 0 0 0.016 1.33e-15 1.27e-13
5 G_PROTEIN_SIGNALING ADCY1, ADCY2, ADCY3, ADCY4, ADCY5, ADCY6, ADCY7, ADCY8, ADCY9, AKAP1, AKAP10, AKAP11, AKAP12, AKAP2, PALM2_AKAP2, AKAP3, AKAP4, AKAP5, AKAP6, AKAP7, AKAP8, AKAP9, ARHGEF1, CALM1, CALM2, CALM3, CHMP1B, GNA11, GNA12, GNA13, GNA14, GNA15, GNAI2, GNAI3, GNAL, GNAO1, GNAQ, GNAZ, GNB1, GNB2, GNB3, GNB5, GNG10, GNG10, LOC552891, GNG12, GNG13, GNG3, GNG4, GNG5, GNG7, GNGT1, GNGT2, HRAS, IL18BP, ITPR1, KCNJ3, KRAS, MGC11266, NRAS, PALM2, PALM2_AKAP2, PALM2_AKAP2, PDE1A, PDE1B, PDE1C, PDE4A, PDE4B, PDE4C, PDE4D, PDE7A, PDE7B, PDE8A, PDE8B, PLCB3, PPP3CA, PPP3CC, PRKACA, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PRKCA, PRKCB1, PRKCD, PRKCE, PRKCG, PRKCH, PRKCI, PRKCQ, PRKCZ, PRKD1, PRKD3, RHOA, RRAS, SARA1, SLC9A1, USP5 92 ADCY3(1), ADCY9(1), AKAP11(1), HRAS(14), ITPR1(1), KRAS(4), NRAS(34), PDE1A(1), PLCB3(1), PRKD1(1), USP5(1) 9015632 60 52 15 2 0 0 39 18 3 0 6.4e-06 2.00e-15 1.27e-13
6 HSA04660_T_CELL_RECEPTOR_SIGNALING_PATHWAY Genes involved in T cell receptor signaling pathway AKT1, AKT2, AKT3, BCL10, CARD11, CBL, CBLB, CBLC, CD247, CD28, CD3D, CD3E, CD3G, CD4, CD40LG, CD8A, CD8B, CDC42, CDK4, CHP, CHUK, CSF2, CTLA4, FOS, FYN, GRAP2, GRB2, HRAS, ICOS, IFNG, IKBKB, IKBKG, IL10, IL2, IL4, IL5, ITK, JUN, KRAS, LAT, LCK, LCP2, MALT1, MAP3K14, MAP3K8, NCK1, NCK2, NFAT5, NFATC1, NFATC2, NFATC3, NFATC4, NFKB1, NFKB2, NFKBIA, NFKBIB, NFKBIE, NRAS, PAK1, PAK2, PAK3, PAK4, PAK6, PAK7, PDCD1, PDK1, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PLCG1, PPP3CA, PPP3CB, PPP3CC, PPP3R1, PPP3R2, PRKCQ, PTPN6, PTPRC, RASGRP1, RHOA, SOS1, SOS2, TEC, TNF, VAV1, VAV2, VAV3, ZAP70 92 HRAS(14), KRAS(4), NRAS(34) 7823189 52 52 7 2 0 0 39 13 0 0 0.000012 2.55e-15 1.27e-13
7 HSA04012_ERBB_SIGNALING_PATHWAY Genes involved in ErbB signaling pathway ABL1, ABL2, AKT1, AKT2, AKT3, ARAF, AREG, BAD, BRAF, BTC, CAMK2A, CAMK2B, CAMK2D, CAMK2G, CBL, CBLB, CBLC, CDKN1A, CDKN1B, CRK, CRKL, EGF, EGFR, EIF4EBP1, ELK1, ERBB2, ERBB3, ERBB4, EREG, FRAP1, GAB1, GRB2, GSK3B, HBEGF, HRAS, JUN, KRAS, MAP2K1, MAP2K2, MAP2K4, MAP2K7, MAPK1, MAPK10, MAPK3, MAPK8, MAPK9, MYC, NCK1, NCK2, NRAS, NRG1, NRG2, NRG3, NRG4, PAK1, PAK2, PAK3, PAK4, PAK6, PAK7, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PLCG1, PLCG2, PRKCA, PRKCB1, PRKCG, PTK2, RAF1, RPS6KB1, RPS6KB2, SHC1, SHC2, SHC3, SHC4, SOS1, SOS2, SRC, STAT5A, STAT5B, TGFA 85 BRAF(1), HRAS(14), KRAS(4), NRAS(34) 7967801 53 52 8 1 0 0 39 14 0 0 1.9e-06 2.66e-15 1.27e-13
8 HSA04664_FC_EPSILON_RI_SIGNALING_PATHWAY Genes involved in Fc epsilon RI signaling pathway AKT1, AKT2, AKT3, BTK, CSF2, FCER1A, FCER1G, FYN, GAB2, GRB2, HRAS, IL13, IL3, IL4, IL5, INPP5D, KRAS, LAT, LCP2, LYN, MAP2K1, MAP2K2, MAP2K3, MAP2K4, MAP2K6, MAP2K7, MAPK1, MAPK10, MAPK11, MAPK12, MAPK13, MAPK14, MAPK3, MAPK8, MAPK9, MS4A2, NRAS, PDK1, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PLA2G10, PLA2G12A, PLA2G12B, PLA2G1B, PLA2G2A, PLA2G2D, PLA2G2E, PLA2G2F, PLA2G3, PLA2G4A, PLA2G5, PLA2G6, PLCG1, PLCG2, PRKCA, PRKCB1, PRKCD, PRKCE, RAC1, RAC2, RAC3, RAF1, SOS1, SOS2, SYK, TNF, VAV1, VAV2, VAV3 74 HRAS(14), KRAS(4), NRAS(34), PLA2G5(1) 5557217 53 52 8 1 0 0 39 14 0 0 5.1e-06 3.00e-15 1.27e-13
9 HSA04530_TIGHT_JUNCTION Genes involved in tight junction ACTB, ACTG1, ACTN1, ACTN2, ACTN3, ACTN4, AKT1, AKT2, AKT3, AMOTL1, ASH1L, CASK, CDC42, CDK4, CGN, CLDN1, CLDN10, CLDN11, CLDN14, CLDN15, CLDN16, CLDN17, CLDN18, CLDN19, CLDN2, CLDN20, CLDN22, CLDN23, CLDN3, CLDN4, CLDN5, CLDN6, CLDN7, CLDN8, CLDN9, CRB3, CSDA, CSNK2A1, CSNK2A2, CSNK2B, CTNNA1, CTNNA2, CTNNA3, CTNNB1, CTTN, EPB41, EPB41L1, EPB41L2, EPB41L3, EXOC3, EXOC4, F11R, GNAI1, GNAI2, GNAI3, HCLS1, HRAS, IGSF5, INADL, JAM2, JAM3, KRAS, LLGL1, LLGL2, MAGI1, MAGI2, MAGI3, MLLT4, MPDZ, MPP5, MRAS, MRCL3, MRLC2, MYH1, MYH10, MYH11, MYH13, MYH14, MYH15, MYH2, MYH3, MYH4, MYH6, MYH7, MYH7B, MYH8, MYH9, MYL2, MYL5, MYL7, MYL8P, MYL9, MYLC2PL, MYLPF, NRAS, OCLN, PARD3, PARD6A, PARD6B, PARD6G, PPM1J, PPP2CA, PPP2CB, PPP2R1A, PPP2R1B, PPP2R2A, PPP2R2B, PPP2R2C, PPP2R3A, PPP2R3B, PPP2R4, PRKCA, PRKCB1, PRKCD, PRKCE, PRKCG, PRKCH, PRKCI, PRKCQ, PRKCZ, PTEN, RAB13, RAB3B, RHOA, RRAS, RRAS2, SPTAN1, SRC, SYMPK, TJAP1, TJP1, TJP2, TJP3, VAPA, YES1, ZAK 131 AMOTL1(1), EPB41L1(1), HRAS(14), KRAS(4), MYH13(1), NRAS(34), PPM1J(1) 14972875 56 52 11 4 2 1 39 14 0 0 0.00018 3.11e-15 1.27e-13
10 HSA04916_MELANOGENESIS Genes involved in melanogenesis ADCY1, ADCY2, ADCY3, ADCY4, ADCY5, ADCY6, ADCY7, ADCY8, ADCY9, ASIP, CALM1, CALM2, CALM3, CALML3, CALML6, CAMK2A, CAMK2B, CAMK2D, CAMK2G, CREB1, CREB3, CREB3L1, CREB3L2, CREB3L3, CREB3L4, CREBBP, CTNNB1, DCT, DVL1, DVL2, DVL3, EDN1, EDNRB, EP300, FZD1, FZD10, FZD2, FZD3, FZD4, FZD5, FZD6, FZD7, FZD8, FZD9, GNAI1, GNAI2, GNAI3, GNAO1, GNAQ, GNAS, GSK3B, HRAS, KIT, KITLG, KRAS, LEF1, LOC652788, MAP2K1, MAP2K2, MAPK1, MAPK3, MC1R, MITF, NRAS, PLCB1, PLCB2, PLCB3, PLCB4, POMC, PRKACA, PRKACB, PRKACG, PRKCA, PRKCB1, PRKCG, PRKX, PRKY, RAF1, TCF7, TCF7L1, TCF7L2, TYR, TYRP1, WNT1, WNT10A, WNT10B, WNT11, WNT16, WNT2, WNT2B, WNT3, WNT3A, WNT4, WNT5A, WNT5B, WNT6, WNT7A, WNT7B, WNT8A, WNT8B, WNT9A, WNT9B 99 ADCY3(1), ADCY9(1), CREB3L3(1), HRAS(14), KRAS(4), MITF(1), NRAS(34), PLCB3(1), TCF7L1(1), WNT11(1), WNT5B(1) 8417028 60 52 15 1 3 0 40 16 1 0 2.2e-06 3.11e-15 1.27e-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 HSA00602_GLYCOSPHINGOLIPID_BIOSYNTHESIS_NEO_LACTOSERIES Genes involved in glycosphingolipid biosynthesis - neo-lactoseries ABO, B3GNT1, B3GNT2, B3GNT3, B3GNT4, B3GNT5, B4GALT1, B4GALT2, B4GALT3, B4GALT4, FUT1, FUT2, FUT3, FUT4, FUT5, FUT6, FUT7, FUT9, GCNT2, ST3GAL6, ST8SIA1 21 ABO(1), B3GNT3(1), FUT3(1) 1247478 3 3 3 0 1 0 1 1 0 0 0.42 0.0056 0.96
2 HSA01031_GLYCAN_STRUCTURES_BIOSYNTHESIS_2 Genes involved in glycan structures - biosynthesis 2 A4GALT, ABO, B3GALNT1, B3GALT1, B3GALT2, B3GALT4, B3GALT5, B3GNT1, B3GNT2, B3GNT3, B3GNT4, B3GNT5, B4GALNT1, B4GALT1, B4GALT2, B4GALT3, B4GALT4, B4GALT6, FUT1, FUT2, FUT3, FUT4, FUT5, FUT6, FUT7, FUT9, GBGT1, GCNT2, PIGA, PIGB, PIGC, PIGF, PIGG, PIGH, PIGK, PIGL, PIGM, PIGN, PIGO, PIGP, PIGQ, PIGS, PIGT, PIGU, PIGV, PIGX, PIGZ, ST3GAL1, ST3GAL2, ST3GAL3, ST3GAL4, ST3GAL5, ST3GAL6, ST6GALNAC3, ST6GALNAC4, ST6GALNAC5, ST6GALNAC6, ST8SIA1, ST8SIA5, UGCG, UGCGL1, UGCGL2 60 ABO(1), B3GNT3(1), FUT3(1), PIGS(1), PIGZ(1) 3739343 5 5 5 0 1 1 2 1 0 0 0.18 0.0067 0.96
3 RNA_TRANSCRIPTION_REACTOME CCNH, CDK7, ERCC3, GTF2A2, GTF2B, GTF2E1, GTF2E2, GTF2F2, GTF2H1, GTF2H2, GTF2H4, ILK, MGC9850, MNAT1, POLR1A, POLR1B, POLR2A, POLR2B, POLR2C, POLR2E, POLR2F, POLR2G, POLR2H, POLR2I, POLR2J, POLR2K, POLR3B, POLR3D, POLR3E, POLR3H, POLR3K, TAF12, TAF13, TAF5, TAF6, TAF7, TAF9, TBP, VARS2L 36 GTF2F2(1), POLR1B(2), POLR3B(1) 2707358 4 4 4 0 0 1 0 1 2 0 0.37 0.0067 0.96
4 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 POLR1B(2), RB1(1) 1566275 3 3 3 0 0 1 0 0 2 0 0.44 0.009 0.96
5 BLOOD_GROUP_GLYCOLIPID_BIOSYNTHESIS_LACTOSERIES ABO, FUT1, FUT2, FUT3, FUT5, FUT6, SIAT6, ST3GAL3 7 ABO(1), FUT3(1) 392806 2 2 2 0 1 0 1 0 0 0 0.54 0.0096 0.96
6 INTRINSICPATHWAY The intrinsic prothrombin activation pathway is activated by traumatized blood vessels and induces clot formation. COL4A1, COL4A2, COL4A3, COL4A4, COL4A5, COL4A6, F10, F11, F12, F2, F2R, F5, F8, F9, FGA, FGB, FGG, KLKB1, KNG, PROC, PROS1, SERPINC1, SERPING1 22 COL4A1(1), COL4A4(1), PROC(1), PROS1(2) 3428221 5 5 5 0 1 0 1 3 0 0 0.22 0.01 0.96
7 HSA03020_RNA_POLYMERASE Genes involved in RNA polymerase POLR1A, POLR1B, POLR1C, POLR1D, POLR2A, POLR2B, POLR2C, POLR2D, POLR2E, POLR2F, POLR2G, POLR2H, POLR2I, POLR2J, POLR2K, POLR2L, POLR3A, POLR3B, POLR3G, POLR3GL, POLR3H, POLR3K, ZNRD1 23 POLR1B(2), POLR3B(1) 1812320 3 3 3 0 0 0 0 1 2 0 0.59 0.011 0.96
8 EXTRINSICPATHWAY The extrinsic prothrombin activation pathway requires the release of thromboplastin from damaged tissues to activate the blood clotting cascade. F10, F2, F2R, F3, F5, F7, FGA, FGB, FGG, PROC, PROS1, SERPINC1, TFPI 13 PROC(1), PROS1(2) 1263139 3 3 3 0 0 0 0 3 0 0 0.6 0.014 0.99
9 VALINE_LEUCINE_AND_ISOLEUCINE_BIOSYNTHESIS BCAT1, IARS, LARS, LARS2, PDHA1, PDHA2, PDHB 7 BCAT1(1), LARS(1) 772351 2 2 2 0 0 0 1 0 1 0 0.67 0.014 0.99
10 HSA00601_GLYCOSPHINGOLIPID_BIOSYNTHESIS_LACTOSERIES Genes involved in glycosphingolipid biosynthesis - lactoseries ABO, B3GALT1, B3GALT2, B3GALT5, B3GNT5, FUT1, FUT2, FUT3, ST3GAL3, ST3GAL4 10 ABO(1), FUT3(1) 556767 2 2 2 0 1 0 1 0 0 0 0.51 0.017 1
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

In addition to the links below, the full results of the analysis summarized in this report can also be downloaded programmatically using firehose_get, or interactively from either the Broad GDAC website or TCGA Data Coordination Center Portal.

References
[1] TCGA, Integrated genomic analyses of ovarian carcinoma, Nature 474:609 - 615 (2011)
Copyright © 2014 Broad Institute TCGA GDAC as part of the TCGA Research Network. All rights reserved.
Made with Nozzle