Rectum Adenocarcinoma: Mutation Analysis (MutSig)
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: READ

  • Number of patients in set: 69

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:READ.final_analysis_set.maf

  • Significantly mutated genes (q ≤ 0.1): 18

  • Mutations seen in COSMIC: 222

  • Significantly mutated genes in COSMIC territory: 10

  • Genes with clustered mutations (≤ 3 aa apart): 0

  • Significantly mutated genesets: 114

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

Mutation Preprocessing

  • Read 38 MAFs of type "Broad"

  • Read 35 MAFs of type "Baylor"

  • Total number of mutations in input MAFs: 29413

  • After removing 257 invalidated mutations: 29156

  • After removing 200 noncoding mutations: 28956

  • After collapsing adjacent/redundant mutations: 21678

Mutation Filtering

  • Number of mutations before filtering: 21678

  • After removing 172 mutations outside gene set: 21506

  • After removing 172 mutations outside category set: 21334

  • After removing 5 "impossible" mutations in

  • gene-patient-category bins of zero coverage: 21329

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 30
Frame_Shift_Del 153
Frame_Shift_Ins 155
In_Frame_Del 27
In_Frame_Ins 7
Missense_Mutation 14491
Nonsense_Mutation 1780
Nonstop_Mutation 6
Read-through 10
Silent 4633
Splice_Site 38
Total 21334
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
*CpG->T 4922 112840423 0.000044 44 5.4
*Cp(A/C/T)->mut 6686 933772624 7.2e-06 7.2 0.88
A->mut 2744 1010264149 2.7e-06 2.7 0.33
*CpG->(G/A) 135 112840423 1.2e-06 1.2 0.15
indel+null 2054 2056877265 1e-06 1 0.12
double_null 157 2056877265 7.6e-08 0.076 0.0094
Total 16698 2056877265 8.1e-06 8.1 1
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: READ.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)->mut

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

  • n4 = number of nonsilent mutations of type: *CpG->(G/A)

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

  • p_classic = p-value for the observed amount of nonsilent mutations 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: 18. 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_ks p_cons p_joint p q
1 APC adenomatous polyposis coli 592848 66 57 56 0 1 4 4 0 39 18 <1.00e-15 2e-07 0.9 0.000022 <0.00 <0.00
2 TP53 tumor protein p53 89473 45 45 30 1 19 6 6 2 12 0 <1.00e-15 2e-07 2e-07 0 <1.00e-15 <4.50e-12
3 KRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog 48783 38 38 8 0 0 36 1 0 1 0 <1.00e-15 2e-07 0.00045 0 <1.00e-15 <4.50e-12
4 MUTYH mutY homolog (E. coli) 118204 2 2 2 2 1 0 0 0 1 0 0.043 0.25 0.022 0 <1.00e-15 <4.50e-12
5 SMAD4 SMAD family member 4 117507 8 8 6 0 2 3 3 0 0 0 4.95e-11 0.16 0.14 0.13 1.78e-10 6.41e-07
6 KIAA1804 165968 11 9 9 0 7 3 1 0 0 0 6.20e-09 0.025 0.011 0.011 1.60e-09 4.80e-06
7 FBXW7 F-box and WD repeat domain containing 7 178296 12 9 10 0 6 2 2 0 2 0 7.57e-09 0.072 0.059 0.058 9.92e-09 0.000026
8 NRAS neuroblastoma RAS viral (v-ras) oncogene homolog 40434 5 5 4 0 0 3 2 0 0 0 7.40e-08 0.012 0.42 0.023 3.61e-08 0.000081
9 TCF7L2 transcription factor 7-like 2 (T-cell specific, HMG-box) 140095 7 7 7 1 2 3 0 0 2 0 1.24e-07 0.061 0.033 0.032 8.10e-08 0.00016
10 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 226803 7 7 7 1 1 3 3 0 0 0 3.04e-07 0.11 0.39 0.15 8.03e-07 0.0014
11 OPCML opioid binding protein/cell adhesion molecule-like 78039 6 6 6 1 1 3 0 0 2 0 2.60e-07 0.47 0.47 0.55 2.39e-06 0.0039
12 SMAD2 SMAD family member 2 99636 5 5 5 0 0 3 1 0 1 0 0.000015 0.012 0.3 0.018 4.18e-06 0.0063
13 SPATA8 spermatogenesis associated 8 22770 3 3 3 0 0 0 3 0 0 0 4.52e-06 0.098 0.49 0.14 9.37e-06 0.013
14 ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian) 261623 4 4 2 1 4 0 0 0 0 0 0.024 0.000088 0.022 0.000049 0.000017 0.022
15 IL1RAPL2 interleukin 1 receptor accessory protein-like 2 144969 5 5 4 2 2 1 0 0 2 0 0.000015 0.12 0.99 0.14 0.000029 0.035
16 KRTAP5-5 keratin associated protein 5-5 38816 2 2 1 0 0 0 0 2 0 0 0.000063 0.08 0.0071 0.039 0.000034 0.038
17 MARCKSL1 MARCKS-like 1 35451 2 2 1 0 0 0 0 0 2 0 0.0012 0.0017 0.17 0.0032 0.000054 0.057
18 FAM123B family with sequence similarity 123B 229757 8 6 8 1 0 2 1 0 5 0 0.00011 0.043 0.65 0.098 0.00013 0.13
19 ZIM3 zinc finger, imprinted 3 99015 6 5 6 0 1 1 3 0 1 0 0.000048 0.44 0.097 0.25 0.00015 0.14
20 PIK3R1 phosphoinositide-3-kinase, regulatory subunit 1 (alpha) 161759 5 4 5 0 2 0 0 0 1 2 0.00046 0.023 0.59 0.027 0.00015 0.14
21 OSBPL6 oxysterol binding protein-like 6 208311 5 5 5 0 1 2 0 2 0 0 0.00018 0.22 0.059 0.076 0.00017 0.14
22 SGCB sarcoglycan, beta (43kDa dystrophin-associated glycoprotein) 65136 4 4 4 0 0 3 0 0 0 1 0.000039 0.28 0.67 0.39 0.00019 0.15
23 LIFR leukemia inhibitory factor receptor alpha 232360 5 5 5 2 0 2 1 1 1 0 0.00023 0.22 0.051 0.075 0.00021 0.16
24 TLL2 tolloid-like 2 211905 3 3 2 2 2 0 1 0 0 0 0.076 0.00013 0.17 0.00027 0.00024 0.18
25 CACNG7 calcium channel, voltage-dependent, gamma subunit 7 58512 3 3 3 0 2 0 0 1 0 0 0.00065 0.49 0.0036 0.032 0.00025 0.18
26 EPYC epiphycan 68517 4 3 4 0 1 1 1 1 0 0 0.00047 0.033 0.45 0.047 0.00026 0.18
27 FAT4 FAT tumor suppressor homolog 4 (Drosophila) 1029673 17 10 17 5 5 8 3 0 1 0 0.00033 0.036 0.45 0.078 0.00030 0.20
28 FBXO15 F-box protein 15 92322 3 3 3 0 2 0 1 0 0 0 0.0024 0.0045 0.28 0.012 0.00033 0.21
29 CCBP2 chemokine binding protein 2 79971 5 5 5 0 1 2 2 0 0 0 0.000036 0.77 0.3 0.8 0.00033 0.21
30 CASP14 caspase 14, apoptosis-related cysteine peptidase 51957 5 4 4 0 4 1 0 0 0 0 0.00013 0.14 0.67 0.24 0.00035 0.21
31 HHEX hematopoietically expressed homeobox 31954 2 2 2 0 0 1 1 0 0 0 0.029 0.0025 0.35 0.0011 0.00036 0.21
32 CSMD3 CUB and Sushi multiple domains 3 791430 11 9 11 6 2 4 2 2 1 0 0.000093 0.42 0.17 0.36 0.00038 0.21
33 REEP2 receptor accessory protein 2 53463 2 2 2 0 0 0 2 0 0 0 0.017 0.51 0.0015 0.002 0.00039 0.21
34 ZNF395 zinc finger protein 395 105838 2 2 1 0 0 0 1 0 1 0 0.036 0.00066 0.77 0.0011 0.00045 0.24
35 SLITRK1 SLIT and NTRK-like family, member 1 144555 6 5 6 0 2 1 2 0 1 0 0.00024 0.13 0.57 0.18 0.00048 0.24
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: 10. Number of genes displayed: 10

rank gene description n cos n_cos N_cos cos_ev p q
1 KRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog 38 51 37 3519 363199 1.6e-14 7.2e-11
2 TP53 tumor protein p53 45 823 45 56787 17987 1.7e-13 2.6e-10
3 APC adenomatous polyposis coli 66 838 50 57822 1039 1.7e-13 2.6e-10
4 NRAS neuroblastoma RAS viral (v-ras) oncogene homolog 5 28 5 1932 5755 7.8e-12 8.8e-09
5 FBXW7 F-box and WD repeat domain containing 7 12 91 6 6279 329 2.3e-11 2.1e-08
6 SMAD4 SMAD family member 4 8 159 6 10971 39 6.4e-10 4.8e-07
7 KRTAP5-5 keratin associated protein 5-5 2 1 2 69 2 1.5e-07 0.0001
8 ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian) 4 41 3 2829 6 2e-06 0.0011
9 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 7 184 4 12696 1382 4.3e-06 0.0022
10 LRP1B low density lipoprotein-related protein 1B (deleted in tumors) 20 18 2 1242 2 5e-05 0.023

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

There were no clustered mutations discovered.

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: 114. 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 q
1 HSA04310_WNT_SIGNALING_PATHWAY Genes involved in Wnt signaling pathway APC, APC2, AXIN1, AXIN2, BTRC, CACYBP, CAMK2A, CAMK2B, CAMK2D, CAMK2G, CCND1, CCND2, CCND3, CER1, CHD8, CHP, CREBBP, CSNK1A1, CSNK1A1L, CSNK1E, CSNK2A1, CSNK2A2, CSNK2B, CTBP1, CTBP2, CTNNB1, CTNNBIP1, CUL1, CXXC4, DAAM1, DAAM2, DKK1, DKK2, DKK4, DVL1, DVL2, DVL3, EP300, FBXW11, FOSL1, FRAT1, FRAT2, FZD1, FZD10, FZD2, FZD3, FZD4, FZD5, FZD6, FZD7, FZD8, FZD9, GSK3B, JUN, LEF1, LOC652788, LRP5, LRP6, MAP3K7, MAPK10, MAPK8, MAPK9, MMP7, MYC, NFAT5, NFATC1, NFATC2, NFATC3, NFATC4, NKD1, NKD2, NLK, PLCB1, PLCB2, PLCB3, PLCB4, PORCN, PPARD, PPP2CA, PPP2CB, PPP2R1A, PPP2R1B, PPP2R2A, PPP2R2B, PPP2R2C, PPP3CA, PPP3CB, PPP3CC, PPP3R1, PPP3R2, PRICKLE1, PRICKLE2, PRKACA, PRKACB, PRKACG, PRKCA, PRKCB1, PRKCG, PRKX, PRKY, PSEN1, RAC1, RAC2, RAC3, RBX1, RHOA, ROCK1, ROCK2, RUVBL1, SENP2, SFRP1, SFRP2, SFRP4, SFRP5, SIAH1, SKP1, SMAD2, SMAD3, SMAD4, SOX17, TBL1X, TBL1XR1, TBL1Y, TCF7, TCF7L1, TCF7L2, TP53, VANGL1, VANGL2, WIF1, WNT1, WNT10A, WNT10B, WNT11, WNT16, WNT2, WNT2B, WNT3, WNT3A, WNT4, WNT5A, WNT5B, WNT6, WNT7A, WNT7B, WNT8A, WNT8B, WNT9A, WNT9B 144 APC(66), AXIN1(1), AXIN2(2), BTRC(3), CACYBP(1), CAMK2D(1), CHD8(2), CREBBP(4), CTNNB1(4), CUL1(1), DAAM1(1), DAAM2(4), DKK1(2), DKK2(1), DKK4(3), DVL2(1), DVL3(2), EP300(2), FBXW11(1), FZD1(1), FZD10(2), FZD3(3), FZD4(1), FZD6(3), GSK3B(1), LRP6(7), MAP3K7(2), MAPK10(4), MAPK8(5), MAPK9(2), MMP7(2), NFATC1(1), NFATC2(2), NFATC3(1), NFATC4(1), PLCB3(1), PLCB4(1), PPARD(1), PPP2CB(2), PPP2R1B(1), PPP2R2B(2), PPP2R2C(1), PPP3CA(2), PPP3CB(1), PPP3CC(1), PRICKLE1(3), PRICKLE2(1), PRKACA(1), PRKACG(1), PRKCA(2), PRKCG(2), RBX1(1), RHOA(1), ROCK1(7), ROCK2(4), RUVBL1(2), SENP2(1), SFRP1(1), SFRP2(2), SFRP4(1), SMAD2(5), SMAD3(3), SMAD4(8), TBL1X(1), TBL1Y(1), TCF7(3), TCF7L2(7), TP53(45), WNT10B(1), WNT2(1), WNT2B(2), WNT6(1), WNT8A(1), WNT9B(1) 16648987 263 68 234 35 68 67 33 3 74 18 <1.00e-15 <1.54e-14
2 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 203 ABI2(1), ACTN1(2), ACTN2(1), ACTN3(1), ACTN4(1), APC(66), ARHGEF1(1), ARHGEF12(2), ARHGEF4(1), ARHGEF6(3), ARPC2(1), ARPC5L(1), BAIAP2(1), BDKRB2(1), BRAF(2), CDC42(1), CHRM2(3), CHRM4(1), CHRM5(1), CSK(2), CYFIP1(1), CYFIP2(1), DIAPH2(3), DIAPH3(2), DOCK1(2), EGFR(1), F2(1), FGD1(2), FGD3(1), FGF11(1), FGF12(1), FGF13(1), FGF19(1), FGF20(1), FGF5(2), FGFR1(1), FGFR2(5), FN1(4), GIT1(1), GRLF1(5), IQGAP1(3), IQGAP2(3), ITGA10(4), ITGA11(2), ITGA2(1), ITGA2B(2), ITGA4(5), ITGA6(1), ITGA8(3), ITGA9(2), ITGAD(1), ITGAE(2), ITGAL(3), ITGAM(3), ITGAV(4), ITGAX(2), ITGB2(1), ITGB3(2), ITGB4(1), ITGB5(1), ITGB8(1), KRAS(38), LIMK1(1), LIMK2(1), MAP2K1(1), MAP2K2(1), MAPK3(1), MOS(1), MSN(3), MYH10(2), MYH14(3), MYH9(3), MYL9(2), MYLK(3), MYLK2(1), NCKAP1(1), NCKAP1L(4), NRAS(5), PAK1(1), PAK2(1), PAK3(2), PAK7(3), PDGFRA(4), PDGFRB(1), PIK3CA(7), PIK3CD(1), PIK3CG(2), PIK3R1(5), PIK3R3(4), PIP5K1B(1), PIP5K1C(1), PPP1CB(1), PPP1CC(1), PPP1R12A(1), PPP1R12B(4), RAF1(2), RDX(1), RHOA(1), ROCK1(7), ROCK2(4), RRAS2(1), SCIN(1), SLC9A1(2), SOS1(2), SOS2(2), SSH1(2), SSH3(1), TIAM1(5), TIAM2(2), VAV1(2), VAV2(2), VAV3(2), VCL(1), WASF1(2), WASL(2) 29141477 332 66 291 70 74 124 38 4 72 20 <1.00e-15 <1.54e-14
3 GSK3PATHWAY Bacterial lipopolysaccharide activates AKT to promote the survival and activation of macrophages and inhibits Gsk3-beta to promote beta-catenin accumulation in the nucleus. AKT1, APC, AXIN1, CCND1, CD14, CTNNB1, DVL1, FZD1, GJA1, GNAI1, GSK3B, IRAK1, LBP, LEF1, LY96, MYD88, NFKB1, PDPK1, PIK3CA, PIK3R1, PPP2CA, PRKR, RELA, TIRAP, TLR4, TOLLIP, WNT1 26 APC(66), AXIN1(1), CTNNB1(4), FZD1(1), GJA1(4), GNAI1(1), GSK3B(1), MYD88(1), NFKB1(3), PIK3CA(7), PIK3R1(5), TLR4(3) 3101261 97 60 87 4 12 15 10 0 40 20 <1.00e-15 <1.54e-14
4 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(66), AR(2), BRAF(2), DAG1(1), EGFR(1), GNAI1(1), GNAQ(1), ITPR1(8), ITPR2(6), ITPR3(1), KCNJ5(1), KCNJ9(1), MAPK10(4), PHKA2(1), PIK3CA(7), PIK3CD(1), PIK3R1(5), RAF1(2) 5604387 111 60 101 7 18 15 11 0 46 21 <1.00e-15 <1.54e-14
5 ALKPATHWAY Activin receptor-like kinase 3 (ALK3) is required during gestation for cardiac muscle development. ACVR1, APC, ATF2, AXIN1, BMP10, BMP2, BMP4, BMP5, BMP7, BMPR1A, BMPR2, CHRD, CTNNB1, DVL1, FZD1, GATA4, GSK3B, MADH1, MADH4, MADH5, MADH6, MAP3K7, MEF2C, MYL2, NKX2-5, NOG, NPPA, NPPB, RFC1, TCF1, TGFB1, TGFB2, TGFB3, TGFBR1, TGFBR2, TGFBR3, WNT1 32 ACVR1(1), APC(66), ATF2(1), AXIN1(1), BMP10(1), BMP2(1), BMP4(1), BMP5(1), BMP7(1), BMPR2(3), CTNNB1(4), FZD1(1), GSK3B(1), MAP3K7(2), MEF2C(2), NPPB(1), RFC1(4), TGFB2(4), TGFBR1(3), TGFBR3(3) 3708540 102 59 92 3 13 19 9 0 43 18 <1.00e-15 <1.54e-14
6 ST_WNT_BETA_CATENIN_PATHWAY Beta-catenin is degraded in the absence of Wnt signaling; when extracellular Wnt binds Frizzled receptors, beta-catenin accumulates in the nucleus and may promote cell survival. AKT1, AKT2, AKT3, ANKRD6, APC, AXIN1, AXIN2, C22orf2, CER1, CSNK1A1, CTNNB1, DACT1, DKK1, DKK2, DKK3, DKK4, DVL1, FRAT1, FSTL1, GSK3A, GSK3B, IDAX, LAMR1, LRP1, MVP, NKD1, NKD2, PIN1, PSEN1, PTPRA, SENP2, SFRP1, TSHB, WIF1 30 AKT2(1), AKT3(1), APC(66), AXIN1(1), AXIN2(2), CTNNB1(4), DACT1(1), DKK1(2), DKK2(1), DKK4(3), FSTL1(1), GSK3B(1), LRP1(3), SENP2(1), SFRP1(1), TSHB(1) 4183619 90 59 80 4 8 14 11 0 39 18 <1.00e-15 <1.54e-14
7 PITX2PATHWAY The bicoid-related transcription factor Pitx2 is activated by Wnt binding to the Frizzled receptor and induces tissue-specific cell proliferation. APC, AXIN1, CREBBP, CTNNB1, DVL1, EP300, FZD1, GSK3B, HDAC1, HTATIP, LDB1, LEF1, PITX2, PPARBP, TRRAP, WNT1 14 APC(66), AXIN1(1), CREBBP(4), CTNNB1(4), EP300(2), FZD1(1), GSK3B(1), LDB1(2), TRRAP(4) 3373014 85 58 75 4 8 12 6 0 41 18 <1.00e-15 <1.54e-14
8 PS1PATHWAY Presenilin is required for gamma-secretase activity to activate Notch signaling; presenilin also inhibits beta-catenin in the Wnt/Frizzled pathway. ADAM17, APC, AXIN1, BTRC, CTNNB1, DLL1, DVL1, FZD1, GSK3B, NOTCH1, PSEN1, RBPSUH, TCF1, WNT1 12 ADAM17(1), APC(66), AXIN1(1), BTRC(3), CTNNB1(4), DLL1(3), FZD1(1), GSK3B(1) 2052660 80 58 70 1 6 8 6 0 42 18 <1.00e-15 <1.54e-14
9 ST_GRANULE_CELL_SURVIVAL_PATHWAY The survival and differentiation of granule cells in the brain is controlled by pro-growth PACAP and pro-apoptotic ceramides. ADPRT, APC, ASAH1, CAMP, CASP3, CERK, CREB1, CREB3, CREB5, CXCL2, DAG1, EPHB2, FOS, GNAQ, IL8RB, ITPKA, ITPKB, JUN, MAP2K4, MAP2K7, MAPK1, MAPK10, MAPK8, MAPK8IP1, MAPK8IP2, MAPK8IP3, MAPK9, PACAP 25 APC(66), CASP3(1), CREB3(1), CREB5(2), DAG1(1), EPHB2(1), FOS(1), GNAQ(1), MAP2K4(2), MAPK10(4), MAPK8(5), MAPK8IP3(1), MAPK9(2) 2881625 88 58 78 3 7 9 7 2 45 18 <1.00e-15 <1.54e-14
10 WNT_SIGNALING Wnt signaling genes APC, ARHA, AXIN1, C2orf31, CCND1, CCND2, CCND3, CSNK1E, CSNK1E, LOC400927, CTNNB1, DIPA, DVL1, DVL2, DVL3, FBXW2, FOSL1, FRAT1, FZD1, FZD10, FZD2, FZD3, FZD5, FZD6, FZD7, FZD8, FZD9, GSK3B, JUN, LDLR, MAPK10, MAPK9, MYC, PAFAH1B1, PLAU, PPP2R5C, PPP2R5E, PRKCA, PRKCB1, PRKCD, PRKCE, PRKCG, PRKCH, PRKCI, PRKCM, PRKCQ, PRKCZ, PRKD1, RAC1, RHOA, SFRP4, TCF7, WNT1, WNT10A, WNT10B, WNT11, WNT16, WNT2, WNT2B, WNT3, WNT4, WNT5A, WNT5B, WNT6, WNT7A, WNT7B 58 APC(66), AXIN1(1), CTNNB1(4), DVL2(1), DVL3(2), FBXW2(1), FZD1(1), FZD10(2), FZD3(3), FZD6(3), GSK3B(1), LDLR(1), MAPK10(4), MAPK9(2), PLAU(1), PPP2R5C(1), PRKCA(2), PRKCE(2), PRKCG(2), PRKCH(1), PRKCQ(1), PRKD1(5), RHOA(1), SFRP4(1), TCF7(3), WNT10B(1), WNT2(1), WNT2B(2), WNT6(1) 6066998 117 58 107 13 15 27 8 0 49 18 <1.00e-15 <1.54e-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 q
1 ERBB4PATHWAY ErbB4 (aka HER4) is a receptor tyrosine kinase that binds neuregulins as well as members of the EGF family, which also target EGF receptors. ADAM17, ERBB4, NRG2, NRG3, PRKCA, PRKCB1, PSEN1 6 ADAM17(1), ERBB4(5), NRG2(2), NRG3(4), PRKCA(2) 933406 14 9 14 1 4 5 1 1 3 0 0.00092 0.24
2 C21_STEROID_HORMONE_METABOLISM AKR1C4, AKR1D1, CYP11A1, CYP11B1, CYP11B2, CYP17A1, CYP21A2, HSD11B1, HSD11B2, HSD3B1, HSD3B2 11 AKR1C4(1), AKR1D1(1), CYP11A1(2), CYP11B1(4), CYP21A2(1), HSD3B1(1), HSD3B2(1) 921900 11 10 11 2 3 5 1 0 2 0 0.0012 0.24
3 HSA00140_C21_STEROID_HORMONE_METABOLISM Genes involved in C21-steroid hormone metabolism AKR1C4, AKR1D1, CYP11A1, CYP11B1, CYP11B2, CYP17A1, CYP21A2, HSD11B1, HSD11B2, HSD3B1, HSD3B2 11 AKR1C4(1), AKR1D1(1), CYP11A1(2), CYP11B1(4), CYP21A2(1), HSD3B1(1), HSD3B2(1) 921900 11 10 11 2 3 5 1 0 2 0 0.0012 0.24
4 HSA00240_PYRIMIDINE_METABOLISM Genes involved in pyrimidine metabolism AICDA, AK3, CAD, CANT1, CDA, CMPK, CTPS, CTPS2, DCK, DCTD, DHODH, DPYD, DPYS, DTYMK, DUT, ECGF1, ENTPD1, ENTPD3, ENTPD4, ENTPD5, ENTPD6, ENTPD8, ITPA, NME1, NME2, NME4, NME6, NME7, NP, NT5C, NT5C1A, NT5C1B, NT5C2, NT5C3, NT5E, NT5M, NUDT2, PNPT1, POLA1, POLA2, POLD1, POLD2, POLD3, POLD4, POLE, POLE2, POLE3, POLE4, POLR1A, POLR1B, POLR1C, POLR1D, POLR2A, POLR2B, POLR2C, POLR2D, POLR2E, POLR2F, POLR2G, POLR2H, POLR2I, POLR2J, POLR2K, POLR2L, POLR3A, POLR3B, POLR3G, POLR3GL, POLR3H, POLR3K, PRIM1, PRIM2, RFC5, RRM1, RRM2, RRM2B, TK1, TK2, TXNRD1, TXNRD2, TYMS, UCK1, UCK2, UMPS, UPB1, UPP1, UPP2, UPRT, ZNRD1 86 AICDA(1), CAD(1), CTPS(1), DCK(1), DHODH(1), DPYD(6), DPYS(1), DTYMK(1), ENTPD5(1), ENTPD6(1), NME6(1), NME7(2), NT5C1B(1), NT5C2(1), NT5E(1), PNPT1(5), POLA1(3), POLE(4), POLE2(1), POLR1A(3), POLR1B(2), POLR2B(3), POLR2K(1), POLR3A(4), POLR3B(5), POLR3K(1), PRIM2(3), RFC5(1), RRM1(1), TK2(1), TXNRD1(1), TXNRD2(1), TYMS(1), UMPS(1), UPB1(2), UPP2(1), UPRT(1) 8537733 67 28 65 15 18 26 10 0 13 0 0.0028 0.36
5 HCMVPATHWAY Cytomegalovirus activates MAP kinase pathways in the host cell, inducing transcription of viral genes. AKT1, CREB1, MAP2K1, MAP2K2, MAP2K3, MAP2K6, MAP3K1, MAPK1, MAPK14, MAPK3, NFKB1, PIK3CA, PIK3R1, RB1, RELA, SP1 15 MAP2K1(1), MAP2K2(1), MAP2K3(4), MAP2K6(1), MAP3K1(2), MAPK3(1), NFKB1(3), PIK3R1(5), RB1(3) 1817823 21 10 21 3 7 4 4 1 3 2 0.0029 0.36
6 CREMPATHWAY The transcription factor CREM activates a post-meiotic transcriptional cascade culminating in spermatogenesis. ADCY1, CREM, FHL5, FSHB, FSHR, GNAS, XPO1 7 ADCY1(4), FHL5(3), FSHB(1), FSHR(1), XPO1(1) 969112 10 9 10 4 4 1 3 1 1 0 0.0043 0.44
7 PAR1PATHWAY Activated extracellular thrombin cleaves and activates the G-protein coupled receptors PAR1 and PAR4, which activate platelets. ADCY1, ARHA, ARHGEF1, F2, F2R, F2RL3, GNA12, GNA13, GNAI1, GNAQ, GNB1, GNGT1, MAP3K7, PIK3CA, PIK3R1, PLCB1, PPP1R12B, PRKCA, PRKCB1, PTK2B, ROCK1 18 ADCY1(4), ARHGEF1(1), F2(1), GNAI1(1), GNAQ(1), GNGT1(1), MAP3K7(2), PIK3R1(5), PPP1R12B(4), PRKCA(2), ROCK1(7) 2455051 29 13 29 7 8 7 5 0 7 2 0.0052 0.46
8 GSPATHWAY Activated G-protein coupled receptors stimulate cAMP production and thus activate protein kinase A, involved in a number of signal transduction pathways. ADCY1, GNAS, GNB1, GNGT1, PRKACA, PRKAR1A 6 ADCY1(4), GNGT1(1), PRKACA(1), PRKAR1A(4) 661717 10 8 10 1 3 4 1 0 2 0 0.0063 0.49
9 HSA00472_D_ARGININE_AND_D_ORNITHINE_METABOLISM Genes involved in D-arginine and D-ornithine metabolism DAO 1 DAO(4) 74796 4 3 4 0 3 1 0 0 0 0 0.0085 0.55
10 NEUROTRANSMITTERSPATHWAY Biosynthesis of neurotransmitters DBH, GAD1, HDC, PNMT, TH, TPH1 6 DBH(1), GAD1(2), HDC(5), TPH1(2) 608603 10 7 10 2 3 5 1 0 1 0 0.0089 0.55
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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