Lung Squamous Cell Carcinoma: 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: LUSC

  • Number of patients in set: 178

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:LUSC.final_analysis_set.maf

  • Significantly mutated genes (q ≤ 0.1): 132

  • Mutations seen in COSMIC: 351

  • Significantly mutated genes in COSMIC territory: 11

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

  • Significantly mutated genesets: 18

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

Mutation Preprocessing

  • Read 178 MAFs of type "Broad"

  • Total number of mutations in input MAFs: 112274

  • After removing 5 mutations outside chr1-24: 112269

  • After removing 48505 noncoding mutations: 63764

  • After collapsing adjacent/redundant mutations: 62900

Mutation Filtering

  • Number of mutations before filtering: 62900

  • After removing 361 mutations outside gene set: 62539

  • After removing 32 mutations outside category set: 62507

Results
Breakdown of Mutations by Type

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

type count
Frame_Shift_Del 521
Frame_Shift_Ins 134
In_Frame_Del 84
In_Frame_Ins 19
Missense_Mutation 41821
Nonsense_Mutation 3567
Nonstop_Mutation 55
Silent 15131
Splice_Site 1152
Translation_Start_Site 23
Total 62507
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
Tp*C->mut 12931 705628846 0.000018 18 2.1 3.3
(A/C/G)p*C->(A/T) 16706 2005408876 8.3e-06 8.3 0.94 2.6
(A/C/G)p*C->G 3292 2005408876 1.6e-06 1.6 0.18 4.9
A->mut 8807 2607765148 3.4e-06 3.4 0.38 3.9
indel+null 5610 5318802870 1.1e-06 1.1 0.12 NaN
double_null 30 5318802870 5.6e-09 0.0056 0.00063 NaN
Total 47376 5318802870 8.9e-06 8.9 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: LUSC.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: Tp*C->mut

  • n2 = number of nonsilent mutations of type: (A/C/G)p*C->(A/T)

  • n3 = number of nonsilent mutations of type: (A/C/G)p*C->G

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

  • 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_ns_s = p-value for the observed nonsilent/silent ratio being elevated in this gene

  • p_ks = p-value for clustering of mutations (Kolmogorov-Smirnoff test)

  • p_cons = p-value for enrichment of mutations at evolutionarily most-conserved sites in gene

  • p_joint = p-value for clustering + conservation

  • p = p-value (overall)

  • q = q-value, False Discovery Rate (Benjamini-Hochberg procedure)

Table 3.  Get Full Table A Ranked List of Significantly Mutated Genes. Number of significant genes found: 132. Number of genes displayed: 35. Click on a gene name to display its stick figure depicting the distribution of mutations and mutation types across the chosen gene (this feature may not be available for all significant genes).

rank gene description N n npat nsite nsil n1 n2 n3 n4 n5 n6 p_classic p_ns_s p_ks p_cons p_joint p q
1 TP53 tumor protein p53 223924 144 140 96 4 8 39 18 32 47 0 <1.00e-15 6.7e-11 2e-07 2e-07 0 <1.00e-15 <4.52e-12
2 NFE2L2 nuclear factor (erythroid-derived 2)-like 2 318442 28 27 15 0 19 4 0 4 1 0 <1.00e-15 0.0071 2e-07 2e-07 0 <1.00e-15 <4.52e-12
3 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 585086 29 27 16 1 20 4 0 5 0 0 1.44e-12 0.021 0.000071 0.00075 0 <1.00e-15 <4.52e-12
4 CDKN2A cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4) 175686 26 26 23 1 5 5 2 2 12 0 <1.00e-15 0.02 0.0019 2.2e-06 0 <1.00e-15 <4.52e-12
5 TPTE transmembrane phosphatase with tensin homology 309720 30 24 29 2 10 4 2 9 5 0 <1.00e-15 0.034 0.61 0.32 0.45 <1.62e-14 <5.87e-11
6 KEAP1 kelch-like ECH-associated protein 1 325562 23 21 21 0 9 8 2 2 2 0 2.35e-12 0.00032 0.058 0.21 0.077 5.50e-12 1.66e-08
7 SI sucrase-isomaltase (alpha-glucosidase) 1009616 46 36 46 2 10 21 2 8 5 0 4.53e-12 0.0067 0.76 0.79 0.94 1.15e-10 2.98e-07
8 PTEN phosphatase and tensin homolog (mutated in multiple advanced cancers 1) 222144 16 14 15 0 4 1 0 3 8 0 1.37e-10 0.11 0.037 0.37 0.064 2.33e-10 5.26e-07
9 TRIM58 tripartite motif-containing 58 197936 15 15 15 1 2 8 1 1 3 0 1.25e-09 0.053 0.01 0.47 0.03 9.38e-10 1.88e-06
10 REG1B regenerating islet-derived 1 beta (pancreatic stone protein, pancreatic thread protein) 92738 11 11 9 1 6 2 0 2 1 0 2.04e-09 0.2 0.33 0.12 0.18 8.56e-09 0.000015
11 OR5L2 olfactory receptor, family 5, subfamily L, member 2 167320 15 13 15 1 0 6 3 5 1 0 8.07e-10 0.068 0.41 0.39 0.49 8.89e-09 0.000015
12 LRRC4C leucine rich repeat containing 4C 343006 19 17 19 1 5 8 1 4 1 0 1.37e-08 0.021 0.073 0.17 0.075 2.22e-08 0.000034
13 FAM5C family with sequence similarity 5, member C 414562 28 27 28 3 3 15 1 9 0 0 1.25e-09 0.043 1 0.96 1 2.68e-08 0.000037
14 ZBBX zinc finger, B-box domain containing 440550 17 17 17 1 4 4 1 5 3 0 5.51e-08 0.13 0.023 0.65 0.038 4.37e-08 0.000056
15 ELTD1 EGF, latrophilin and seven transmembrane domain containing 1 375046 18 18 18 1 4 3 1 4 6 0 3.59e-09 0.081 0.46 0.78 0.68 5.10e-08 0.000062
16 DPPA4 developmental pluripotency associated 4 167854 12 12 12 0 4 3 1 0 4 0 8.80e-09 0.057 0.31 0.48 0.43 7.64e-08 0.000086
17 ASB5 ankyrin repeat and SOCS box-containing 5 181204 9 9 9 0 3 1 3 2 0 0 5.81e-06 0.14 0.013 0.0038 0.00074 8.70e-08 0.000093
18 OR4M2 olfactory receptor, family 4, subfamily M, member 2 168388 14 14 14 2 2 6 0 5 1 0 7.22e-09 0.2 0.93 0.8 1 1.43e-07 0.00014
19 PDYN prodynorphin 137594 8 8 8 0 2 3 2 1 0 0 0.000020 0.09 0.0005 0.33 0.00063 2.44e-07 0.00023
20 CYP11B1 cytochrome P450, family 11, subfamily B, polypeptide 1 275544 15 15 15 1 0 11 1 3 0 0 1.25e-07 0.031 0.094 0.9 0.2 4.57e-07 0.00041
21 OR2G6 olfactory receptor, family 2, subfamily G, member 6 169990 15 15 15 3 3 5 0 7 0 0 3.86e-07 0.22 0.042 0.34 0.067 4.81e-07 0.00041
22 CRB1 crumbs homolog 1 (Drosophila) 759882 27 23 27 2 8 6 1 9 3 0 1.25e-07 0.043 0.14 0.81 0.27 6.19e-07 0.00051
23 KRTAP5-5 keratin associated protein 5-5 120684 9 9 6 1 0 3 1 0 5 0 5.44e-07 0.53 0.023 1 0.069 6.84e-07 0.00054
24 OR6F1 olfactory receptor, family 6, subfamily F, member 1 165718 13 13 13 2 2 6 1 4 0 0 2.44e-07 0.19 0.32 0.14 0.18 7.95e-07 0.00060
25 USP29 ubiquitin specific peptidase 29 493594 18 17 18 1 3 6 2 4 3 0 2.21e-07 0.075 0.87 0.24 0.53 1.98e-06 0.0014
26 ESRRG estrogen-related receptor gamma 250090 12 12 12 1 2 5 1 2 2 0 1.03e-06 0.13 0.082 0.5 0.12 2.17e-06 0.0015
27 MAGEB2 melanoma antigen family B, 2 129406 9 9 9 1 2 4 2 1 0 0 3.22e-07 0.27 0.6 0.45 0.57 3.03e-06 0.0020
28 CFHR4 complement factor H-related 4 181560 10 10 10 1 0 4 1 3 2 0 7.60e-07 0.35 0.41 0.36 0.44 5.38e-06 0.0035
29 C20orf26 chromosome 20 open reading frame 26 679426 21 19 21 1 4 11 1 3 2 0 7.76e-06 0.017 0.024 0.34 0.049 6.00e-06 0.0037
30 SLC13A1 solute carrier family 13 (sodium/sulfate symporters), member 1 328944 12 12 12 1 4 2 1 4 1 0 3.40e-06 0.15 0.066 0.51 0.12 6.36e-06 0.0038
31 PNLIPRP3 pancreatic lipase-related protein 3 258456 11 11 11 1 1 5 2 1 2 0 2.94e-06 0.38 0.13 0.22 0.15 6.90e-06 0.0040
32 OR51B2 olfactory receptor, family 51, subfamily B, member 2 167854 10 10 10 0 2 3 1 3 1 0 1.08e-06 0.077 0.37 0.36 0.47 7.86e-06 0.0044
33 HS6ST1 heparan sulfate 6-O-sulfotransferase 1 172838 5 5 5 0 1 2 0 0 2 0 0.014 0.12 0.00017 0.0058 0.000055 0.000011 0.0061
34 REG3G regenerating islet-derived 3 gamma 97544 8 8 8 1 1 3 0 0 4 0 1.23e-06 0.26 0.47 0.42 0.64 0.000012 0.0061
35 CPS1 carbamoyl-phosphate synthetase 1, mitochondrial 832506 27 24 26 2 4 14 1 6 2 0 3.69e-06 0.025 0.13 0.9 0.21 0.000012 0.0061
TP53

Figure S1.  This figure depicts the distribution of mutations and mutation types across the TP53 significant gene.

NFE2L2

Figure S2.  This figure depicts the distribution of mutations and mutation types across the NFE2L2 significant gene.

PIK3CA

Figure S3.  This figure depicts the distribution of mutations and mutation types across the PIK3CA significant gene.

CDKN2A

Figure S4.  This figure depicts the distribution of mutations and mutation types across the CDKN2A significant gene.

TPTE

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

KEAP1

Figure S6.  This figure depicts the distribution of mutations and mutation types across the KEAP1 significant gene.

SI

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

PTEN

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

TRIM58

Figure S9.  This figure depicts the distribution of mutations and mutation types across the TRIM58 significant gene.

REG1B

Figure S10.  This figure depicts the distribution of mutations and mutation types across the REG1B significant gene.

OR5L2

Figure S11.  This figure depicts the distribution of mutations and mutation types across the OR5L2 significant gene.

LRRC4C

Figure S12.  This figure depicts the distribution of mutations and mutation types across the LRRC4C significant gene.

FAM5C

Figure S13.  This figure depicts the distribution of mutations and mutation types across the FAM5C significant gene.

ZBBX

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

ELTD1

Figure S15.  This figure depicts the distribution of mutations and mutation types across the ELTD1 significant gene.

DPPA4

Figure S16.  This figure depicts the distribution of mutations and mutation types across the DPPA4 significant gene.

ASB5

Figure S17.  This figure depicts the distribution of mutations and mutation types across the ASB5 significant gene.

OR4M2

Figure S18.  This figure depicts the distribution of mutations and mutation types across the OR4M2 significant gene.

CYP11B1

Figure S19.  This figure depicts the distribution of mutations and mutation types across the CYP11B1 significant gene.

OR2G6

Figure S20.  This figure depicts the distribution of mutations and mutation types across the OR2G6 significant gene.

CRB1

Figure S21.  This figure depicts the distribution of mutations and mutation types across the CRB1 significant gene.

KRTAP5-5

Figure S22.  This figure depicts the distribution of mutations and mutation types across the KRTAP5-5 significant gene.

OR6F1

Figure S23.  This figure depicts the distribution of mutations and mutation types across the OR6F1 significant gene.

USP29

Figure S24.  This figure depicts the distribution of mutations and mutation types across the USP29 significant gene.

ESRRG

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

MAGEB2

Figure S26.  This figure depicts the distribution of mutations and mutation types across the MAGEB2 significant gene.

CFHR4

Figure S27.  This figure depicts the distribution of mutations and mutation types across the CFHR4 significant gene.

C20orf26

Figure S28.  This figure depicts the distribution of mutations and mutation types across the C20orf26 significant gene.

SLC13A1

Figure S29.  This figure depicts the distribution of mutations and mutation types across the SLC13A1 significant gene.

PNLIPRP3

Figure S30.  This figure depicts the distribution of mutations and mutation types across the PNLIPRP3 significant gene.

OR51B2

Figure S31.  This figure depicts the distribution of mutations and mutation types across the OR51B2 significant gene.

HS6ST1

Figure S32.  This figure depicts the distribution of mutations and mutation types across the HS6ST1 significant gene.

REG3G

Figure S33.  This figure depicts the distribution of mutations and mutation types across the REG3G significant gene.

COSMIC analyses

In this analysis, COSMIC is used as a filter to increase power by restricting the territory of each gene. Cosmic version: v48.

Table 4.  Get Full Table Significantly mutated genes (COSMIC territory only). To access the database please go to: COSMIC. Number of significant genes found: 11. Number of genes displayed: 10

rank gene description n cos n_cos N_cos cos_ev p q
1 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 29 184 24 32752 9572 1.2e-12 2.5e-09
2 TP53 tumor protein p53 144 308 141 54824 25449 1.7e-12 2.5e-09
3 CDKN2A cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4) 26 315 25 56070 559 1.7e-12 2.5e-09
4 PTEN phosphatase and tensin homolog (mutated in multiple advanced cancers 1) 16 728 16 129584 579 2.2e-12 2.5e-09
5 FBXW7 F-box and WD repeat domain containing 7 11 91 6 16198 220 1.1e-08 1e-05
6 HRAS v-Ha-ras Harvey rat sarcoma viral oncogene homolog 4 19 4 3382 802 3.3e-08 0.000025
7 RB1 retinoblastoma 1 (including osteosarcoma) 12 267 7 47526 17 3.3e-07 0.00022
8 HEPACAM2 4 1 2 178 2 1.2e-06 0.00071
9 NF1 neurofibromin 1 (neurofibromatosis, von Recklinghausen disease, Watson disease) 22 285 6 50730 21 8e-06 0.004
10 BRAF v-raf murine sarcoma viral oncogene homolog B1 8 88 4 15664 77 0.000014 0.0064

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: 18. 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(3), ATM(8), ATR(13), CCNA1(1), CCND1(1), CCNE1(3), CDKN1A(2), CDKN2A(26), CDKN2B(1), E2F1(2), HDAC1(2), RB1(12), SKP2(2), TFDP1(3), TGFB1(1), TGFB2(3), TP53(144) 8137626 227 156 176 13 28 65 23 40 71 0 5.9e-11 <1.00e-15 <4.40e-14
2 ARFPATHWAY Cyclin-dependent kinase inhibitor 2A is a tumor suppressor that induces G1 arrest and can activate the p53 pathway, leading to G2/M arrest. ABL1, CDKN2A, E2F1, MDM2, MYC, PIK3CA, PIK3R1, POLR1A, POLR1B, POLR1C, POLR1D, RAC1, RB1, TBX2, TP53, TWIST1 16 ABL1(3), CDKN2A(26), E2F1(2), MDM2(2), MYC(1), PIK3CA(29), PIK3R1(2), POLR1A(3), POLR1B(2), POLR1D(1), RAC1(1), RB1(12), TBX2(3), TP53(144) 5471186 231 155 167 15 42 56 20 44 69 0 5.9e-11 <1.00e-15 <4.40e-14
3 P53HYPOXIAPATHWAY Hypoxia induces p53 accumulation and consequent apoptosis with p53-mediated cell cycle arrest, which is present under conditions of DNA damage. ABCB1, AKT1, ATM, BAX, CDKN1A, CPB2, CSNK1A1, CSNK1D, FHL2, GADD45A, HIC1, HIF1A, HSPA1A, HSPCA, IGFBP3, MAPK8, MDM2, NFKBIB, NQO1, TP53 19 ABCB1(17), AKT1(1), ATM(8), BAX(1), CDKN1A(2), CPB2(3), CSNK1A1(2), CSNK1D(2), FHL2(1), GADD45A(1), HIF1A(1), IGFBP3(2), MAPK8(2), MDM2(2), NFKBIB(1), TP53(144) 5574960 190 150 142 8 26 53 19 40 51 1 4.3e-11 <1.00e-15 <4.40e-14
4 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 AKT1(1), APAF1(4), ATM(8), BAX(1), BCL2L1(1), CASP7(2), CASP9(3), PRKCA(5), PTK2(6), PXN(3), STAT1(2), TLN1(6), TP53(144) 7347662 186 148 137 16 24 51 22 40 49 0 8.4e-07 <1.00e-15 <4.40e-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(4), ATM(8), BAX(1), CCND1(1), CCNE1(3), CDKN1A(2), E2F1(2), GADD45A(1), MDM2(2), RB1(12), TP53(144) 4870970 180 148 132 5 16 50 19 38 57 0 5.7e-12 <1.00e-15 <4.40e-14
6 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 ARF1(1), CCND1(1), CDKN1A(2), CDKN2A(26), CFL1(2), E2F1(2), MDM2(2), NXT1(1), PRB1(4), TP53(144) 2299938 185 148 134 9 17 52 20 37 59 0 1.8e-11 <1.00e-15 <4.40e-14
7 TELPATHWAY Telomerase is a ribonucleotide protein that adds telomeric repeats to the 3' ends of chromosomes. AKT1, BCL2, EGFR, G22P1, HSPCA, IGF1R, KRAS2, MYC, POLR2A, PPP2CA, PRKCA, RB1, TEP1, TERF1, TERT, TNKS, TP53, XRCC5 15 AKT1(1), EGFR(7), IGF1R(1), MYC(1), POLR2A(2), PRKCA(5), RB1(12), TEP1(7), TERF1(3), TERT(3), TNKS(7), TP53(144), XRCC5(2) 7526196 195 148 146 14 23 52 19 42 59 0 1.5e-09 <1.00e-15 <4.40e-14
8 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(8), ATR(13), CDC25C(1), CHEK1(5), CHEK2(3), TP53(144) 4288732 174 146 126 6 17 48 21 37 51 0 1.8e-09 <1.00e-15 <4.40e-14
9 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(17), DAXX(3), HRAS(4), PAX3(4), RARA(1), RB1(12), SIRT1(1), SP100(3), TNF(1), TNFRSF1A(2), TNFRSF1B(1), TP53(144) 5147404 193 146 145 14 16 55 22 42 58 0 8.9e-09 <1.00e-15 <4.40e-14
10 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(8), CDC25B(2), CDC25C(1), CHEK1(5), MYT1(4), RB1(12), TP53(144), WEE1(4) 4718424 180 145 132 7 17 50 20 36 57 0 2.6e-10 <1.00e-15 <4.40e-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 HSA00627_1,4_DICHLOROBENZENE_DEGRADATION Genes involved in 1,4-dichlorobenzene degradation CMBL 1 CMBL(3) 134924 3 3 3 1 0 1 0 2 0 0 0.81 0.037 1
2 HSA00902_MONOTERPENOID_BIOSYNTHESIS Genes involved in monoterpenoid biosynthesis CYP2C19, CYP2C9 2 CYP2C19(8), CYP2C9(3) 537026 11 10 11 3 5 3 0 2 1 0 0.55 0.17 1
3 SA_G2_AND_M_PHASES Cdc25 activates the cdc2/cyclin B complex to induce the G2/M transition. CDC2, CDC25A, CDC25B, CDK7, CDKN1A, CHEK1, NEK1, WEE1 7 CDC25B(2), CDK7(1), CDKN1A(2), CHEK1(5), NEK1(3), WEE1(4) 1922578 17 17 17 1 7 5 1 3 1 0 0.1 0.25 1
4 HSA00750_VITAMIN_B6_METABOLISM Genes involved in vitamin B6 metabolism AOX1, PDXK, PDXP, PNPO, PSAT1 5 AOX1(13), PDXP(1), PSAT1(3) 1297976 17 16 17 2 6 5 0 5 1 0 0.13 0.26 1
5 HSA00472_D_ARGININE_AND_D_ORNITHINE_METABOLISM Genes involved in D-arginine and D-ornithine metabolism DAO 1 DAO(2) 192952 2 2 2 0 0 1 0 0 1 0 0.5 0.34 1
6 HSA00550_PEPTIDOGLYCAN_BIOSYNTHESIS Genes involved in peptidoglycan biosynthesis GLUL, PGLYRP2 2 GLUL(4), PGLYRP2(2) 488788 6 5 6 0 1 4 1 0 0 0 0.15 0.36 1
7 FBW7PATHWAY Cyclin E interacts with cell cycle checkpoint kinase cdk2 to allow transcription of genes required for S phase, including transcription of additional cyclin E. CCNE1, CDC34, CDK2, CUL1, E2F1, FBXW7, RB1, SKP1A, TFDP1 7 CCNE1(3), CUL1(4), E2F1(2), FBXW7(11), TFDP1(3) 1763624 23 23 21 4 6 8 3 1 5 0 0.25 0.42 1
8 P27PATHWAY p27 blocks the G1/S transition by inhibiting the checkpoint kinase cdk2/cyclin E and is inhibited by cdk2-mediated ubiquitination. CCNE1, CDK2, CDKN1B, CKS1B, CUL1, E2F1, NEDD8, RB1, RBX1, SKP1A, SKP2, TFDP1, UBE2M 11 CCNE1(3), CKS1B(1), CUL1(4), E2F1(2), RBX1(1), SKP2(2), TFDP1(3), UBE2M(1) 1828772 17 16 17 1 5 8 0 2 2 0 0.05 0.43 1
9 HSA00780_BIOTIN_METABOLISM Genes involved in biotin metabolism BTD, HLCS, SPCS1, SPCS3 4 BTD(2), HLCS(5), SPCS1(1), SPCS3(2) 826632 10 9 10 2 2 2 2 0 4 0 0.4 0.47 1
10 IL18PATHWAY Pro-inflammatory IL-18 is activated in macrophages by caspase-1 cleavage and, in conjunction with IL-12, stimulates Th1 cell differentiation. CASP1, IFNG, IL12A, IL12B, IL18, IL2 6 CASP1(1), IFNG(1), IL12A(1), IL12B(3) 802958 6 6 6 1 3 1 0 0 2 0 0.52 0.52 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

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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