Rectum 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: 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): 17

  • Mutations seen in COSMIC: 222

  • Significantly mutated genes in COSMIC territory: 10

  • Genes with clustered mutations (≤ 3 aa apart): 117

  • 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

  • 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_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: 17. 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 <0.000 <0.000
2 TP53 tumor protein p53 89473 45 45 30 1 19 6 6 2 12 0 3.66e-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 1.89e-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 0.0426 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 4.55e-11 0.16 0.14 0.14 1.64e-10 5.91e-07
6 KIAA1804 165968 11 9 9 0 7 3 1 0 0 0 5.78e-09 0.025 0.011 0.011 1.50e-09 4.49e-06
7 FBXW7 F-box and WD repeat domain containing 7 178296 12 9 10 0 6 2 2 0 2 0 7.15e-09 0.072 0.059 0.058 9.39e-09 2.42e-05
8 NRAS neuroblastoma RAS viral (v-ras) oncogene homolog 40434 5 5 4 0 0 3 2 0 0 0 7.03e-08 0.012 0.42 0.023 3.44e-08 7.74e-05
9 TCF7L2 transcription factor 7-like 2 (T-cell specific, HMG-box) 140095 7 7 7 1 2 3 0 0 2 0 1.17e-07 0.061 0.033 0.032 7.65e-08 0.000153
10 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 226803 7 7 7 1 1 3 3 0 0 0 2.94e-07 0.11 0.39 0.15 7.77e-07 0.00140
11 OPCML opioid binding protein/cell adhesion molecule-like 78039 6 6 6 1 1 3 0 0 2 0 2.42e-07 0.47 0.47 0.55 2.23e-06 0.00366
12 SMAD2 SMAD family member 2 99636 5 5 5 0 0 3 1 0 1 0 1.42e-05 0.012 0.3 0.018 4.04e-06 0.00606
13 SPATA8 spermatogenesis associated 8 22770 3 3 3 0 0 0 3 0 0 0 4.44e-06 0.098 0.48 0.14 9.21e-06 0.0128
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 0.0238 0.000088 0.022 0.000049 1.70e-05 0.0219
15 IL1RAPL2 interleukin 1 receptor accessory protein-like 2 144969 5 5 4 2 2 1 0 0 2 0 1.40e-05 0.12 0.99 0.14 2.78e-05 0.0334
16 KRTAP5-5 keratin associated protein 5-5 38816 2 2 1 0 0 0 0 2 0 0 6.12e-05 0.08 0.0071 0.038 3.29e-05 0.0370
17 MARCKSL1 MARCKS-like 1 35451 2 2 1 0 0 0 0 0 2 0 0.00123 0.0017 0.17 0.0032 5.28e-05 0.0560
18 FAM123B family with sequence similarity 123B 229757 8 6 8 1 0 2 1 0 5 0 0.000105 0.043 0.65 0.098 0.000128 0.128
19 ZIM3 zinc finger, imprinted 3 99015 6 5 6 0 1 1 3 0 1 0 4.61e-05 0.44 0.096 0.25 0.000144 0.134
20 PIK3R1 phosphoinositide-3-kinase, regulatory subunit 1 (alpha) 161759 5 4 5 0 2 0 0 0 1 2 0.000441 0.023 0.59 0.027 0.000149 0.134
21 OSBPL6 oxysterol binding protein-like 6 208311 5 5 5 0 1 2 0 2 0 0 0.000176 0.22 0.059 0.076 0.000164 0.140
22 SGCB sarcoglycan, beta (43kDa dystrophin-associated glycoprotein) 65136 4 4 4 0 0 3 0 0 0 1 3.82e-05 0.28 0.67 0.4 0.000182 0.149
23 LIFR leukemia inhibitory factor receptor alpha 232360 5 5 5 2 0 2 1 1 1 0 0.000225 0.22 0.051 0.075 0.000202 0.158
24 TLL2 tolloid-like 2 211905 3 3 2 2 2 0 1 0 0 0 0.0753 0.00014 0.18 0.00027 0.000240 0.173
25 CACNG7 calcium channel, voltage-dependent, gamma subunit 7 58512 3 3 3 0 2 0 0 1 0 0 0.000639 0.49 0.0036 0.032 0.000241 0.173
26 EPYC epiphycan 68517 4 3 4 0 1 1 1 1 0 0 0.000465 0.033 0.45 0.047 0.000257 0.178
27 FAT4 FAT tumor suppressor homolog 4 (Drosophila) 1029673 17 10 17 5 5 8 3 0 1 0 0.000303 0.036 0.45 0.078 0.000275 0.184
28 CCBP2 chemokine binding protein 2 79971 5 5 5 0 1 2 2 0 0 0 3.51e-05 0.77 0.3 0.8 0.000320 0.199
29 FBXO15 F-box protein 15 92322 3 3 3 0 2 0 1 0 0 0 0.00232 0.0045 0.28 0.012 0.000321 0.199
30 CASP14 caspase 14, apoptosis-related cysteine peptidase 51957 5 4 4 0 4 1 0 0 0 0 0.000125 0.14 0.68 0.24 0.000344 0.201
31 HHEX hematopoietically expressed homeobox 31954 2 2 2 0 0 1 1 0 0 0 0.0283 0.0025 0.35 0.0011 0.000355 0.201
32 CSMD3 CUB and Sushi multiple domains 3 791430 11 9 11 6 2 4 2 2 1 0 8.66e-05 0.42 0.17 0.36 0.000357 0.201
33 REEP2 receptor accessory protein 2 53463 2 2 2 0 0 0 2 0 0 0 0.0169 0.51 0.0015 0.002 0.000387 0.211
34 ZNF395 zinc finger protein 395 105838 2 2 1 0 0 0 1 0 1 0 0.0356 0.00066 0.77 0.0011 0.000452 0.238
35 SLITRK1 SLIT and NTRK-like family, member 1 144555 6 5 6 0 2 1 2 0 1 0 0.000237 0.14 0.57 0.18 0.000462 0.238
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

Table 5.  Get Full Table Genes with Clustered Mutations

num gene desc n mindist nmuts0 nmuts3 nmuts12 npairs0 npairs3 npairs12
3882 KRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog 38 0 278 416 445 278 416 445
7563 TP53 tumor protein p53 45 0 37 61 105 37 61 105
393 APC adenomatous polyposis coli 66 0 11 21 47 11 21 47
2623 FBXW7 F-box and WD repeat domain containing 7 12 0 6 6 6 6 6 6
4886 NRAS neuroblastoma RAS viral (v-ras) oncogene homolog 5 0 6 6 6 6 6 6
6854 SMAD4 SMAD family member 4 8 0 4 4 6 4 4 6
2368 ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian) 4 0 3 3 3 3 3 3
3792 KIAA1804 11 0 2 6 7 2 6 7
3475 IL1RAPL2 interleukin 1 receptor accessory protein-like 2 5 0 1 3 3 1 3 3
2089 DNAH5 dynein, axonemal, heavy chain 5 19 0 1 2 2 1 2 2

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: 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 <6.22e-14
2 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 <6.22e-14
3 ST_JNK_MAPK_PATHWAY JNKs are MAP kinases regulated by several levels of kinases (MAPKK, MAPKKK) and phosphorylate transcription factors and regulatory proteins. AKT1, ATF2, CDC42, DLD, DUSP10, DUSP4, DUSP8, GAB1, GADD45A, GCK, IL1R1, JUN, MAP2K4, MAP2K5, MAP2K7, MAP3K1, MAP3K10, MAP3K11, MAP3K12, MAP3K13, MAP3K2, MAP3K3, MAP3K4, MAP3K5, MAP3K7, MAP3K7IP1, MAP3K7IP2, MAP3K9, MAPK10, MAPK7, MAPK8, MAPK9, MYEF2, NFATC3, NR2C2, PAPPA, SHC1, TP53, TRAF6, ZAK 38 ATF2(1), CDC42(1), DLD(1), DUSP10(1), GCK(1), IL1R1(1), MAP2K4(2), MAP2K5(2), MAP3K1(2), MAP3K10(1), MAP3K12(2), MAP3K13(1), MAP3K2(1), MAP3K3(1), MAP3K4(3), MAP3K5(1), MAP3K7(2), MAP3K9(2), MAPK10(4), MAPK8(5), MAPK9(2), NFATC3(1), PAPPA(5), TP53(45), ZAK(2) 5206358 90 54 75 11 34 19 12 3 22 0 <1.00e-15 <6.22e-14
4 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 ATM(10), ATR(4), CCNA1(2), CDK4(1), CDKN1B(2), DHFR(1), GSK3B(1), RB1(3), TGFB2(4), TP53(45) 3112957 73 51 58 11 24 18 10 2 18 1 <1.00e-15 <6.22e-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(1), ATM(10), CDK4(1), PCNA(1), RB1(3), TIMP3(1), TP53(45) 1905683 62 50 47 6 21 14 9 2 15 1 <1.00e-15 <6.22e-14
6 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(10), ATR(4), BRCA1(1), BRCA2(11), FANCA(2), FANCD2(4), FANCF(1), FANCG(2), MRE11A(5), RAD17(2), RAD50(6), TP53(45) 4587794 93 49 78 7 27 31 16 2 16 1 <1.00e-15 <6.22e-14
7 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(4), DAXX(1), PAX3(2), PML(1), RB1(3), SIRT1(1), TP53(45) 1965067 57 49 42 5 26 7 8 2 14 0 <1.00e-15 <6.22e-14
8 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 CDK4(1), CDKN1B(2), PRB1(1), TP53(45) 831472 49 48 34 2 20 6 6 2 15 0 <1.00e-15 <6.22e-14
9 RNAPATHWAY dsRNA-activated protein kinase phosphorylates elF2a, which generally inhibits translation, and activates NF-kB to provoke inflammation. CHUK, DNAJC3, EIF2S1, EIF2S2, MAP3K14, NFKB1, NFKBIA, PRKR, RELA, TP53 9 CHUK(2), MAP3K14(1), NFKB1(3), TP53(45) 1059846 51 47 36 3 22 7 8 2 12 0 <1.00e-15 <6.22e-14
10 APOPTOSIS_GENMAPP APAF1, BAK1, BCL2L7P1, BAX, BCL2, BCL2L1, BID, BIRC2, BIRC3, BIRC4, CASP2, CASP3, CASP6, CASP7, CASP8, CASP9, CYCS, FADD, FAS, FASLG, GZMB, IKBKG, JUN, MAP2K4, MAP3K1, MAP3K14, MAPK10, MCL1, MDM2, MYC, NFKB1, NFKBIA, PARP1, PRF1, RELA, RIPK1, TNF, TNFRSF1A, TNFRSF1B, TNFSF10, TP53, TRADD, TRAF1, TRAF2 41 APAF1(1), BIRC2(2), BIRC3(5), CASP3(1), CASP6(1), FAS(2), GZMB(1), MAP2K4(2), MAP3K1(2), MAP3K14(1), MAPK10(4), NFKB1(3), TP53(45), TRAF1(1) 3868503 71 49 56 8 27 12 11 2 19 0 1.11e-15 6.22e-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 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 0.00089 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 0.0027 0.35
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 0.0028 0.35
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 0.0041 0.42
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 0.45
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 0.48
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 0.0084 0.54
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 0.0087 0.54
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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