Mutation Analysis (MutSig v2.0)
Uterine Carcinosarcoma (Primary solid tumor)
28 January 2016  |  analyses__2016_01_28
Maintainer Information
Citation Information
doi:10.7908/C1T43SMM
Maintained by David Heiman (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2016): Mutation Analysis (MutSig v2.0). Broad Institute of MIT and Harvard. doi:10.7908/C1T43SMM
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: UCS-TP

  • Number of patients in set: 57

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:UCS-TP.final_analysis_set.maf

  • Blacklist used for this analysis: pancan_mutation_blacklist.v14.hg19.txt

  • Significantly mutated genes (q ≤ 0.1): 16

  • Mutations seen in COSMIC: 138

  • Significantly mutated genes in COSMIC territory: 12

  • Significantly mutated genesets: 103

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

Mutation Preprocessing

  • Read 57 MAFs of type "maf1"

  • Total number of mutations in input MAFs: 11339

  • After removing 78 mutations outside chr1-24: 11261

  • After removing 432 blacklisted mutations: 10829

  • After removing 1059 noncoding mutations: 9770

Mutation Filtering

  • Number of mutations before filtering: 9770

  • After removing 532 mutations outside gene set: 9238

  • After removing 38 mutations outside category set: 9200

Results
Breakdown of Mutations by Type

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

type count
De_novo_Start_InFrame 4
De_novo_Start_OutOfFrame 11
Frame_Shift_Del 235
Frame_Shift_Ins 79
In_Frame_Del 64
In_Frame_Ins 9
Missense_Mutation 6007
Nonsense_Mutation 581
Nonstop_Mutation 11
Silent 1905
Splice_Site 282
Start_Codon_Del 1
Start_Codon_SNP 11
Total 9200
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 1670 95243737 0.000018 18 4 2.1
*Cp(A/C/T)->T 806 765648006 1.1e-06 1.1 0.24 1.7
C->(G/A) 1843 860891743 2.1e-06 2.1 0.49 4.7
A->mut 1699 819427697 2.1e-06 2.1 0.48 3.9
indel+null 1245 1680319440 7.4e-07 0.74 0.17 NaN
double_null 32 1680319440 1.9e-08 0.019 0.0044 NaN
Total 7295 1680319440 4.3e-06 4.3 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). If the figure is unpopulated, then full coverage is assumed (e.g. MutSig CV doesn't use WIGs and assumes full coverage).

Figure 1. 

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

Figure 2.  Patients counts and rates file used to generate this plot: UCS-TP.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: C->(G/A)

  • n4 = number of nonsilent mutations of type: A->mut

  • 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: 16. 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 PPP2R1A protein phosphatase 2 (formerly 2A), regulatory subunit A , alpha isoform 99487 17 16 10 0 7 3 7 0 0 0 7.99e-15 0.0015 0.000055 0.018 0.000029 0.000 0.000
2 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 186411 22 20 13 0 3 5 4 10 0 0 6.33e-15 0.0057 0.012 0.0027 0.00074 2.22e-16 2.01e-12
3 TP53 tumor protein p53 68846 55 51 43 0 14 5 11 12 12 1 2.55e-15 6.6e-07 0 0 0 <1.00e-15 <3.62e-12
4 FBXW7 F-box and WD repeat domain containing 7 139842 24 22 15 0 12 4 5 1 2 0 <1.00e-15 0.0031 2e-07 0.001 0 <1.00e-15 <3.62e-12
5 KRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog 36696 7 7 2 0 0 2 5 0 0 0 8.33e-15 0.35 0 0.047 0 <1.00e-15 <3.62e-12
6 PTEN phosphatase and tensin homolog (mutated in multiple advanced cancers 1) 64171 15 11 14 0 1 2 4 2 5 1 5.88e-15 0.042 0.15 0.73 0.28 5.67e-14 1.71e-10
7 CHD4 chromodomain helicase DNA binding protein 4 336006 12 10 12 0 2 1 0 6 3 0 8.84e-09 0.037 0.089 0.037 0.053 1.06e-08 2.73e-05
8 PIK3R1 phosphoinositide-3-kinase, regulatory subunit 1 (alpha) 134194 8 6 8 0 0 1 0 0 7 0 3.12e-08 0.69 0.02 0.56 0.042 2.78e-08 6.29e-05
9 ZBTB7B zinc finger and BTB domain containing 7B 92321 7 6 7 0 1 0 2 1 3 0 2.38e-08 0.25 0.38 0.022 0.077 3.87e-08 7.80e-05
10 SPOP speckle-type POZ protein 66102 5 4 5 0 1 0 2 2 0 0 3.66e-06 0.35 0.018 0.12 0.022 1.38e-06 0.00250
11 RB1 retinoblastoma 1 (including osteosarcoma) 133287 6 6 6 0 0 0 0 1 4 1 1.65e-07 0.4 0.78 0.7 1 2.74e-06 0.00451
12 NDUFAF2 NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, assembly factor 2 23615 3 3 1 0 0 0 0 0 3 0 5.98e-06 0.29 NaN NaN NaN 5.98e-06 0.00903
13 YARS tyrosyl-tRNA synthetase 92520 3 3 3 0 1 0 2 0 0 0 0.000592 0.45 0.0018 0.3 0.0022 1.93e-05 0.0269
14 CDK11A cyclin-dependent kinase 11A 72275 3 2 3 0 1 0 1 1 0 0 0.00446 0.47 0.0036 0.022 0.00062 3.83e-05 0.0495
15 GPRASP1 G protein-coupled receptor associated sorting protein 1 238270 4 4 4 1 1 1 1 0 1 0 0.000796 0.8 0.0015 0.31 0.004 4.30e-05 0.0520
16 ARID1A AT rich interactive domain 1A (SWI-like) 336825 8 7 8 0 1 0 2 1 3 1 4.41e-06 0.16 0.49 0.81 1 5.88e-05 0.0665
17 MGAM maltase-glucoamylase (alpha-glucosidase) 289007 7 6 7 1 2 1 1 2 1 0 9.21e-06 0.34 0.99 0.59 1 0.000116 0.124
18 MAGEC2 melanoma antigen family C, 2 64182 5 4 5 0 0 1 4 0 0 0 1.55e-05 0.3 0.61 0.95 0.8 0.000152 0.153
19 FAM92B family with sequence similarity 92, member B 52370 3 3 3 0 0 1 1 0 1 0 0.000300 0.35 0.35 0.015 0.044 0.000163 0.155
20 ALCAM activated leukocyte cell adhesion molecule 103047 3 3 3 0 0 0 1 1 1 0 0.000257 0.67 0.027 0.54 0.057 0.000178 0.161
21 HCFC1R1 host cell factor C1 regulator 1 (XPO1 dependent) 18746 2 2 2 0 0 0 0 0 2 0 4.66e-05 1 0.21 0.61 0.35 0.000197 0.170
22 DPP10 dipeptidyl-peptidase 10 138928 5 4 5 1 0 0 2 2 1 0 0.000466 0.64 0.017 0.77 0.039 0.000217 0.173
23 BCL2L11 BCL2-like 11 (apoptosis facilitator) 34712 2 2 1 0 0 0 0 0 2 0 0.000300 1 0.012 0.096 0.062 0.000220 0.173
24 TREX2 three prime repair exonuclease 2 22043 2 2 2 0 0 2 0 0 0 0 0.000234 0.27 NaN NaN NaN 0.000234 0.177
25 U2AF1 U2 small nuclear RNA auxiliary factor 1 46802 2 2 1 0 0 2 0 0 0 0 0.000813 0.38 0.016 0.0084 0.031 0.000289 0.209
26 ATP4A ATPase, H+/K+ exchanging, alpha polypeptide 177895 5 5 5 0 3 0 1 0 1 0 4.76e-05 0.19 0.93 0.82 1 0.000522 0.364
27 SYCP2 synaptonemal complex protein 2 241280 4 4 4 0 0 1 1 2 0 0 0.00165 0.42 0.085 0.034 0.037 0.000653 0.438
28 COPB1 coatomer protein complex, subunit beta 1 160279 4 4 4 0 1 2 1 0 0 0 0.000547 0.36 0.098 0.66 0.12 0.000677 0.438
29 PDGFRB platelet-derived growth factor receptor, beta polypeptide 189225 4 4 4 1 1 1 1 1 0 0 0.000994 0.52 0.29 0.045 0.088 0.000906 0.566
30 FOXA2 forkhead box A2 64487 3 3 3 0 1 0 1 0 1 0 0.000227 0.32 0.27 0.83 0.42 0.000980 0.592
31 ERBB3 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) 239091 5 4 5 0 2 1 1 0 1 0 0.000500 0.21 0.64 0.07 0.22 0.00110 0.645
32 TMUB2 transmembrane and ubiquitin-like domain containing 2 53523 3 3 3 0 2 1 0 0 0 0 0.000541 0.31 0.8 0.054 0.24 0.00129 0.733
33 MAMLD1 mastermind-like domain containing 1 135529 4 4 3 0 0 0 1 2 1 0 0.000397 0.49 0.22 0.58 0.34 0.00134 0.735
34 MMEL1 membrane metallo-endopeptidase-like 1 117524 3 3 3 0 1 1 1 0 0 0 0.00151 0.27 0.042 0.54 0.1 0.00154 0.800
35 SLC10A6 solute carrier family 10 (sodium/bile acid cotransporter family), member 6 65602 3 2 3 0 0 2 0 0 1 0 0.0105 0.4 0.061 0.0088 0.015 0.00154 0.800
PPP2R1A

Figure S1.  This figure depicts the distribution of mutations and mutation types across the PPP2R1A significant gene.

PIK3CA

Figure S2.  This figure depicts the distribution of mutations and mutation types across the PIK3CA significant gene.

TP53

Figure S3.  This figure depicts the distribution of mutations and mutation types across the TP53 significant gene.

FBXW7

Figure S4.  This figure depicts the distribution of mutations and mutation types across the FBXW7 significant gene.

KRAS

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

PTEN

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

CHD4

Figure S7.  This figure depicts the distribution of mutations and mutation types across the CHD4 significant gene.

PIK3R1

Figure S8.  This figure depicts the distribution of mutations and mutation types across the PIK3R1 significant gene.

ZBTB7B

Figure S9.  This figure depicts the distribution of mutations and mutation types across the ZBTB7B significant gene.

SPOP

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

RB1

Figure S11.  This figure depicts the distribution of mutations and mutation types across the RB1 significant gene.

YARS

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

CDK11A

Figure S13.  This figure depicts the distribution of mutations and mutation types across the CDK11A significant gene.

GPRASP1

Figure S14.  This figure depicts the distribution of mutations and mutation types across the GPRASP1 significant gene.

ARID1A

Figure S15.  This figure depicts the distribution of mutations and mutation types across the ARID1A 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: 12. Number of genes displayed: 10

rank gene description n cos n_cos N_cos cos_ev p q
1 FBXW7 F-box and WD repeat domain containing 7 24 91 19 5187 788 0 0
2 TP53 tumor protein p53 55 356 52 20292 16225 0 0
3 KRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog 7 52 7 2964 101988 0 0
4 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 22 220 20 12540 8438 0 0
5 PTEN phosphatase and tensin homolog (mutated in multiple advanced cancers 1) 15 767 15 43719 769 0 0
6 PIK3R1 phosphoinositide-3-kinase, regulatory subunit 1 (alpha) 8 33 4 1881 9 1.8e-10 1.4e-07
7 ERBB3 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) 5 6 2 342 2 1.1e-06 0.00071
8 RB1 retinoblastoma 1 (including osteosarcoma) 6 267 3 15219 10 0.000046 0.026
9 F13A1 coagulation factor XIII, A1 polypeptide 1 1 1 57 1 0.00025 0.093
10 FERD3L Fer3-like (Drosophila) 2 1 1 57 1 0.00025 0.093

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)

Geneset Analyses

Table 5.  Get Full Table A Ranked List of Significantly Mutated Genesets. (Source: MSigDB GSEA Cannonical Pathway Set).Number of significant genesets found: 103. 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 G1PATHWAY CDK4/6-cyclin D and CDK2-cyclin E phosphorylate Rb, which allows the transcription of genes needed for the G1/S cell cycle transition. ABL1, ATM, ATR, CCNA1, CCND1, CCNE1, CDC2, CDC25A, CDK2, CDK4, CDK6, CDKN1A, CDKN1B, CDKN2A, CDKN2B, DHFR, E2F1, GSK3B, HDAC1, MADH3, MADH4, RB1, SKP2, TFDP1, TGFB1, TGFB2, TGFB3, TP53 25 ABL1(1), ATM(3), ATR(3), CCNA1(1), CCND1(1), CDK6(1), CDKN2A(1), CDKN2B(1), E2F1(1), RB1(6), TGFB1(1), TP53(55) 2540817 75 53 63 2 18 6 14 18 17 2 5.1e-07 <1.00e-15 <8.39e-14
2 RBPATHWAY The ATM protein kinase recognizes DNA damage and blocks cell cycle progression by phosphorylating chk1 and p53, which normally inhibits Rb to allow G1/S transitions. ATM, CDC2, CDC25A, CDC25B, CDC25C, CDK2, CDK4, CHEK1, MYT1, RB1, TP53, WEE1, YWHAH 12 ATM(3), RB1(6), TP53(55), WEE1(1) 1464466 65 53 53 1 14 5 12 15 17 2 2.8e-06 <1.00e-15 <8.39e-14
3 G2PATHWAY Activated Cdc2-cyclin B kinase regulates the G2/M transition; DNA damage stimulates the DNA-PK/ATM/ATR kinases, which inactivate Cdc2. ATM, ATR, BRCA1, CCNB1, CDC2, CDC25A, CDC25B, CDC25C, CDC34, CDKN1A, CDKN2D, CHEK1, CHEK2, EP300, GADD45A, MDM2, MYT1, PLK, PRKDC, RPS6KA1, TP53, WEE1, YWHAH, YWHAQ 22 ATM(3), ATR(3), CHEK2(2), EP300(1), PRKDC(2), TP53(55), WEE1(1) 3513011 67 52 55 3 15 6 13 16 16 1 0.000036 <1.00e-15 <8.39e-14
4 PMLPATHWAY Ring-shaped PML nuclear bodies regulate transcription and are required co-activators in p53- and DAXX-mediated apoptosis. CREBBP, DAXX, HRAS, PAX3, PML, PRAM-1, RARA, RB1, SIRT1, SP100, TNF, TNFRSF1A, TNFRSF1B, TNFRSF6, TNFSF6, TP53, UBL1 13 CREBBP(6), PML(1), RB1(6), SIRT1(1), TP53(55) 1613841 69 52 57 0 18 6 12 14 17 2 5.6e-09 <1.00e-15 <8.39e-14
5 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(3), CCND1(1), E2F1(1), RB1(6), TP53(55) 1513923 68 53 56 0 16 6 12 14 18 2 2.9e-08 1.33e-15 8.39e-14
6 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(3), ATR(3), CHEK2(2), TP53(55) 1333162 63 52 51 2 15 5 13 15 14 1 0.000086 1.67e-15 8.39e-14
7 SA_G1_AND_S_PHASES Cdk2, 4, and 6 bind cyclin D in G1, while cdk2/cyclin E promotes the G1/S transition. ARF1, ARF3, CCND1, CDK2, CDK4, CDKN1A, CDKN1B, CDKN2A, CFL1, E2F1, E2F2, MDM2, NXT1, PRB1, TP53 15 CCND1(1), CDKN2A(1), E2F1(1), TP53(55) 728452 58 52 46 0 15 6 12 12 12 1 9e-08 1.78e-15 8.39e-14
8 MTORPATHWAY Mammalian target of rapamycin (mTOR) senses mitogenic factors and nutrients, including ATP, and induces cell proliferation. AKT1, EIF3S10, EIF4A1, EIF4A2, EIF4B, EIF4E, EIF4EBP1, EIF4G1, EIF4G2, EIF4G3, FKBP1A, FRAP1, MKNK1, PDK2, PDPK1, PIK3CA, PIK3R1, PPP2CA, PTEN, RPS6, RPS6KB1, TSC1, TSC2 21 EIF4B(1), EIF4G1(1), EIF4G2(1), EIF4G3(1), PDK2(1), PIK3CA(22), PIK3R1(8), PTEN(15), TSC1(1) 2341534 51 30 41 1 4 9 10 14 13 1 0.000073 1.78e-15 8.39e-14
9 CHEMICALPATHWAY DNA damage promotes Bid cleavage, which stimulates mitochondrial cytochrome c release and consequent caspase activation, resulting in apoptosis. ADPRT, AKT1, APAF1, ATM, BAD, BAX, BCL2, BCL2L1, BID, CASP3, CASP6, CASP7, CASP9, CYCS, EIF2S1, PRKCA, PRKCB1, PTK2, PXN, STAT1, TLN1, TP53 20 APAF1(2), ATM(3), BCL2L1(1), CASP7(1), EIF2S1(1), PXN(1), STAT1(1), TP53(55) 2302234 65 53 53 2 16 6 14 13 15 1 4.3e-06 1.89e-15 8.39e-14
10 ATRBRCAPATHWAY BRCA1 and 2 block cell cycle progression in response to DNA damage and promote double-stranded break repair; mutations induce breast cancer susceptibility. ATM, ATR, BRCA1, BRCA2, CHEK1, CHEK2, FANCA, FANCC, FANCD2, FANCE, FANCF, FANCG, HUS1, MRE11A, NBS1, RAD1, RAD17, RAD50, RAD51, RAD9A, TP53, TREX1 21 ATM(3), ATR(3), BRCA2(4), CHEK2(2), FANCC(1), FANCD2(1), FANCE(1), FANCF(1), FANCG(1), HUS1(1), MRE11A(1), RAD9A(1), TP53(55) 3685680 75 52 63 4 16 7 18 18 15 1 0.000074 1.89e-15 8.39e-14

Table 6.  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 ACTINYPATHWAY The Arp 2/3 complex localizes to the Y-junction of polymerizing actin fibers that enable lamellipod extension and consequent cell motility. ABI-2, ACTA1, ACTR2, ACTR3, ARPC1A, ARPC1B, ARPC2, ARPC3, ARPC4, NCK1, NCKAP1, NTRK1, PIR, PSMA7, RAC1, WASF1, WASF2, WASF3, WASL 18 ACTA1(1), ACTR3(1), NCK1(2), NCKAP1(3), NTRK1(2), PSMA7(1), RAC1(1), WASF1(1), WASF3(1), WASL(1) 1290167 14 9 14 1 5 1 4 1 3 0 0.074 0.0018 0.95
2 IL5PATHWAY Pro-inflammatory IL-5 is secretes by activated T cells, eosinophils, and mast cells, and stimulates the proliferation and activation of eosinophils in bone marrow. CCL11, CCR3, CD4, HLA-DRA, HLA-DRB1, IL1B, IL4, IL5, IL5RA, IL6 10 CCR3(2), HLA-DRA(1), IL1B(2), IL5RA(1) 453522 6 5 6 0 2 1 3 0 0 0 0.14 0.004 0.95
3 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@ 15 CD3E(1), CD80(2), CD86(1), HLA-DRA(1), IL2(1), ITK(1), PTPN11(1) 765001 8 6 8 0 3 2 1 2 0 0 0.072 0.0046 0.95
4 ASBCELLPATHWAY B cells require interaction with helper T cells to produce antigen-specific immunoglobulins as a key element of the human immune response. CD28, CD4, CD80, HLA-DRA, HLA-DRB1, IL10, IL2, IL4, TNFRSF5, TNFRSF6, TNFSF5, TNFSF6 8 CD80(2), HLA-DRA(1), IL2(1) 337807 4 4 4 0 2 1 1 0 0 0 0.23 0.0074 1
5 PARKINPATHWAY In Parkinson's disease, dopaminergic neurons contain Lewy bodies consisting of alpha-synuclein and parkin, an E3 ubiquitin ligase that targets glycosylated alpha-synuclein. GPR37, PARK2, PNUTL1, SNCA, SNCAIP, UBE2E2, UBE2F, UBE2G1, UBE2G2, UBE2L3, UBE2L6, UBL1 10 GPR37(3), SNCAIP(2), UBE2G1(2) 546771 7 5 7 1 2 2 1 1 1 0 0.28 0.015 1
6 SA_PROGRAMMED_CELL_DEATH Programmed cell death, or apoptosis, eliminates damaged or unneeded cells. APAF1, BAD, BAK1, BAX, BCL10, BCL2, BCL2L1, BCL2L11, BID, CASP8AP2, CASP9, CES1 12 APAF1(2), BCL10(1), BCL2L1(1), BCL2L11(2) 919398 6 6 5 1 2 1 0 0 3 0 0.49 0.016 1
7 TOB1PATHWAY TGF-beta signaling activates SMADs, which interact with intracellular Tob to maintain unstimulated T cells by repressing IL-2 expression. CD28, CD3D, CD3E, CD3G, CD3Z, IFNG, IL2, IL2RA, IL4, MADH3, MADH4, TGFB1, TGFB2, TGFB3, TGFBR1, TGFBR2, TGFBR3, TOB1, TOB2, TRA@, TRB@ 16 CD3E(1), IL2(1), IL2RA(1), TGFB1(1), TGFBR3(1), TOB2(1) 897887 6 6 6 0 2 2 0 1 1 0 0.12 0.017 1
8 EOSINOPHILSPATHWAY Recruitment of eosinophils in the inflammatory response observed in asthma occurs via the chemoattractant eotaxin binding to the CCR3 receptor. CCL11, CCL5, CCR3, CSF2, HLA-DRA, HLA-DRB1, IL3, IL5 8 CCR3(2), HLA-DRA(1) 259845 3 3 3 0 1 1 1 0 0 0 0.32 0.029 1
9 ERBB3PATHWAY Neuregulins bind to the receptor tyrosine kinases ErbB3 and ErbB4, surface-localized receptors whose overexpression induces tumor formation. EGF, EGFR, ERBB3, NRG1, UBE2D1 5 EGF(2), ERBB3(5), NRG1(1) 875639 8 5 8 1 2 1 4 0 1 0 0.32 0.036 1
10 HSA00052_GALACTOSE_METABOLISM Genes involved in galactose metabolism AKR1B1, AKR1B10, B4GALT1, B4GALT2, G6PC, G6PC2, GAA, GALE, GALK1, GALK2, GALT, GANC, GCK, GLA, GLB1, HK1, HK2, HK3, HSD3B7, LALBA, LCT, MGAM, PFKL, PFKM, PFKP, PGM1, PGM3, RDH11, RDH12, RDH13, RDH14, UGP2 32 B4GALT2(1), GAA(1), GCK(1), GLA(1), HK2(1), LCT(2), MGAM(7), PFKL(1), PFKP(1), PGM3(1), RDH14(2), UGP2(1) 3288784 20 13 20 3 5 4 4 4 3 0 0.081 0.038 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)
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