Lung Squamous Cell Carcinoma: 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: LUSC-TP

  • 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-TP.final_analysis_set.maf

  • Significantly mutated genes (q ≤ 0.1): 131

  • Mutations seen in COSMIC: 351

  • Significantly mutated genes in COSMIC territory: 11

  • Genes with clustered mutations (≤ 3 aa apart): 376

  • 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 30155 blacklisted mutations: 82114

  • After removing 18682 noncoding mutations: 63432

  • After collapsing adjacent/redundant mutations: 62568

Mutation Filtering

  • Number of mutations before filtering: 62568

  • After removing 333 mutations outside gene set: 62235

  • After removing 32 mutations outside category set: 62203

Results
Breakdown of Mutations by Type

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

type count
Frame_Shift_Del 513
Frame_Shift_Ins 120
In_Frame_Del 46
In_Frame_Ins 3
Missense_Mutation 41684
Nonsense_Mutation 3556
Nonstop_Mutation 55
Silent 15068
Splice_Site 1138
Translation_Start_Site 20
Total 62203
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 12915 705628846 0.000018 18 2.1 3.3
(A/C/G)p*C->(A/T) 16647 2005408876 8.3e-06 8.3 0.94 2.6
(A/C/G)p*C->G 3286 2005408876 1.6e-06 1.6 0.18 4.9
A->mut 8750 2607765148 3.4e-06 3.4 0.38 3.9
indel+null 5507 5318802870 1e-06 1 0.12 NaN
double_null 30 5318802870 5.6e-09 0.0056 0.00064 NaN
Total 47135 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-TP.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

  • 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: 131. 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_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 NaN NaN <1.00e-15 <1.81e-11
2 CDKN2A cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4) 175686 26 26 23 1 5 5 2 2 12 0 6.55e-15 0.02 NaN NaN 6.55e-15 4.82e-11
3 NFE2L2 nuclear factor (erythroid-derived 2)-like 2 318442 28 27 15 0 19 4 0 4 1 0 9.21e-15 0.0071 NaN NaN 9.21e-15 4.82e-11
4 TPTE transmembrane phosphatase with tensin homology 309720 30 24 29 2 10 4 2 9 5 0 1.07e-14 0.034 NaN NaN 1.07e-14 4.82e-11
5 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 585086 29 27 16 1 20 4 0 5 0 0 1.09e-12 0.021 NaN NaN 1.09e-12 3.94e-09
6 KEAP1 kelch-like ECH-associated protein 1 325562 23 21 21 0 9 8 2 2 2 0 1.92e-12 0.00032 NaN NaN 1.92e-12 5.79e-09
7 SI sucrase-isomaltase (alpha-glucosidase) 1009616 46 36 46 2 10 21 2 8 5 0 3.12e-12 0.0067 NaN NaN 3.12e-12 8.07e-09
8 PTEN phosphatase and tensin homolog (mutated in multiple advanced cancers 1) 222144 16 14 15 0 4 1 0 3 8 0 1.06e-10 0.11 NaN NaN 1.06e-10 2.41e-07
9 OR5L2 olfactory receptor, family 5, subfamily L, member 2 167320 15 13 15 1 0 6 3 5 1 0 6.73e-10 0.068 NaN NaN 6.73e-10 1.35e-06
10 FAM5C family with sequence similarity 5, member C 414562 28 27 28 3 3 15 1 9 0 0 9.62e-10 0.043 NaN NaN 9.62e-10 1.74e-06
11 TRIM58 tripartite motif-containing 58 197936 15 15 15 1 2 8 1 1 3 0 1.06e-09 0.053 NaN NaN 1.06e-09 1.74e-06
12 REG1B regenerating islet-derived 1 beta (pancreatic stone protein, pancreatic thread protein) 92738 11 11 9 1 6 2 0 2 1 0 1.78e-09 0.2 NaN NaN 1.78e-09 2.68e-06
13 ELTD1 EGF, latrophilin and seven transmembrane domain containing 1 375046 18 18 18 1 4 3 1 4 6 0 2.96e-09 0.081 NaN NaN 2.96e-09 4.12e-06
14 OR4M2 olfactory receptor, family 4, subfamily M, member 2 168388 14 14 14 2 2 6 0 5 1 0 6.16e-09 0.2 NaN NaN 6.16e-09 7.96e-06
15 DPPA4 developmental pluripotency associated 4 167854 12 12 12 0 4 3 1 0 4 0 7.62e-09 0.057 NaN NaN 7.62e-09 9.20e-06
16 LRRC4C leucine rich repeat containing 4C 343006 19 17 19 1 5 8 1 4 1 0 1.17e-08 0.021 NaN NaN 1.17e-08 1.33e-05
17 ZBBX zinc finger, B-box domain containing 440550 17 17 17 1 4 4 1 5 3 0 4.39e-08 0.13 NaN NaN 4.39e-08 4.67e-05
18 CRB1 crumbs homolog 1 (Drosophila) 759882 27 23 27 2 8 6 1 9 3 0 1.03e-07 0.043 NaN NaN 1.03e-07 0.000104
19 CYP11B1 cytochrome P450, family 11, subfamily B, polypeptide 1 275544 15 15 15 0 0 11 1 3 0 0 1.09e-07 0.006 NaN NaN 1.09e-07 0.000104
20 USP29 ubiquitin specific peptidase 29 493594 18 17 18 1 3 6 2 4 3 0 1.95e-07 0.075 NaN NaN 1.95e-07 0.000176
21 OR6F1 olfactory receptor, family 6, subfamily F, member 1 165718 13 13 13 2 2 6 1 4 0 0 2.15e-07 0.19 NaN NaN 2.15e-07 0.000185
22 MAGEB2 melanoma antigen family B, 2 129406 9 9 9 1 2 4 2 1 0 0 2.85e-07 0.27 NaN NaN 2.85e-07 0.000235
23 OR2G6 olfactory receptor, family 2, subfamily G, member 6 169990 15 15 15 3 3 5 0 7 0 0 3.34e-07 0.22 NaN NaN 3.34e-07 0.000263
24 CFHR4 complement factor H-related 4 181560 10 10 10 1 0 4 1 3 2 0 6.81e-07 0.35 NaN NaN 6.81e-07 0.000513
25 ESRRG estrogen-related receptor gamma 250090 12 12 12 1 2 5 1 2 2 0 9.25e-07 0.13 NaN NaN 9.25e-07 0.000662
26 OR51B2 olfactory receptor, family 51, subfamily B, member 2 167854 10 10 10 0 2 3 1 3 1 0 9.51e-07 0.076 NaN NaN 9.51e-07 0.000662
27 REG3G regenerating islet-derived 3 gamma 97544 8 8 8 1 1 3 0 0 4 0 1.08e-06 0.26 NaN NaN 1.08e-06 0.000725
28 OR2T33 olfactory receptor, family 2, subfamily T, member 33 171948 14 13 14 3 2 6 1 4 1 0 1.26e-06 0.27 NaN NaN 1.26e-06 0.000813
29 PNLIPRP3 pancreatic lipase-related protein 3 258456 11 11 11 1 1 5 2 1 2 0 2.67e-06 0.38 NaN NaN 2.67e-06 0.00163
30 SPHKAP SPHK1 interactor, AKAP domain containing 915632 34 25 34 3 5 15 5 8 1 0 2.70e-06 0.019 NaN NaN 2.70e-06 0.00163
31 SLC13A1 solute carrier family 13 (sodium/sulfate symporters), member 1 328944 12 12 12 1 4 2 1 4 1 0 3.07e-06 0.15 NaN NaN 3.07e-06 0.00179
32 CPS1 carbamoyl-phosphate synthetase 1, mitochondrial 832506 27 24 26 2 4 14 1 6 2 0 3.22e-06 0.025 NaN NaN 3.22e-06 0.00182
33 ASB5 ankyrin repeat and SOCS box-containing 5 181204 9 9 9 0 3 1 3 2 0 0 5.29e-06 0.14 NaN NaN 5.29e-06 0.00290
34 TGIF2LX TGFB-induced factor homeobox 2-like, X-linked 129940 10 8 10 1 2 1 0 5 2 0 6.38e-06 0.32 NaN NaN 6.38e-06 0.00339
35 C20orf26 chromosome 20 open reading frame 26 679426 21 19 21 1 4 11 1 3 2 0 6.64e-06 0.017 NaN NaN 6.64e-06 0.00343
TP53

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

CDKN2A

Figure S2.  This figure depicts the distribution of mutations and mutation types across the CDKN2A significant gene.

NFE2L2

Figure S3.  This figure depicts the distribution of mutations and mutation types across the NFE2L2 significant gene.

TPTE

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

PIK3CA

Figure S5.  This figure depicts the distribution of mutations and mutation types across the PIK3CA 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.

OR5L2

Figure S9.  This figure depicts the distribution of mutations and mutation types across the OR5L2 significant gene.

FAM5C

Figure S10.  This figure depicts the distribution of mutations and mutation types across the FAM5C significant gene.

TRIM58

Figure S11.  This figure depicts the distribution of mutations and mutation types across the TRIM58 significant gene.

REG1B

Figure S12.  This figure depicts the distribution of mutations and mutation types across the REG1B significant gene.

ELTD1

Figure S13.  This figure depicts the distribution of mutations and mutation types across the ELTD1 significant gene.

OR4M2

Figure S14.  This figure depicts the distribution of mutations and mutation types across the OR4M2 significant gene.

DPPA4

Figure S15.  This figure depicts the distribution of mutations and mutation types across the DPPA4 significant gene.

LRRC4C

Figure S16.  This figure depicts the distribution of mutations and mutation types across the LRRC4C significant gene.

ZBBX

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

CRB1

Figure S18.  This figure depicts the distribution of mutations and mutation types across the CRB1 significant gene.

CYP11B1

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

USP29

Figure S20.  This figure depicts the distribution of mutations and mutation types across the USP29 significant gene.

OR6F1

Figure S21.  This figure depicts the distribution of mutations and mutation types across the OR6F1 significant gene.

MAGEB2

Figure S22.  This figure depicts the distribution of mutations and mutation types across the MAGEB2 significant gene.

OR2G6

Figure S23.  This figure depicts the distribution of mutations and mutation types across the OR2G6 significant gene.

CFHR4

Figure S24.  This figure depicts the distribution of mutations and mutation types across the CFHR4 significant gene.

ESRRG

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

OR51B2

Figure S26.  This figure depicts the distribution of mutations and mutation types across the OR51B2 significant gene.

REG3G

Figure S27.  This figure depicts the distribution of mutations and mutation types across the REG3G significant gene.

OR2T33

Figure S28.  This figure depicts the distribution of mutations and mutation types across the OR2T33 significant gene.

PNLIPRP3

Figure S29.  This figure depicts the distribution of mutations and mutation types across the PNLIPRP3 significant gene.

SPHKAP

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

SLC13A1

Figure S31.  This figure depicts the distribution of mutations and mutation types across the SLC13A1 significant gene.

CPS1

Figure S32.  This figure depicts the distribution of mutations and mutation types across the CPS1 significant gene.

ASB5

Figure S33.  This figure depicts the distribution of mutations and mutation types across the ASB5 significant gene.

TGIF2LX

Figure S34.  This figure depicts the distribution of mutations and mutation types across the TGIF2LX 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 29 220 24 39160 9572 1.9e-13 3.7e-10
2 CDKN2A cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4) 26 332 25 59096 559 2.4e-13 3.7e-10
3 TP53 tumor protein p53 144 356 141 63368 25449 2.5e-13 3.7e-10
4 PTEN phosphatase and tensin homolog (mutated in multiple advanced cancers 1) 16 767 16 136526 579 6e-13 6.8e-10
5 FBXW7 F-box and WD repeat domain containing 7 11 91 6 16198 220 1.1e-08 9.7e-06
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 3.2e-07 0.00021
8 HEPACAM2 HEPACAM family member 2 4 1 2 178 2 1.2e-06 0.0007
9 NF1 neurofibromin 1 (neurofibromatosis, von Recklinghausen disease, Watson disease) 22 285 6 50730 21 7.8e-06 0.0039
10 BRAF v-raf murine sarcoma viral oncogene homolog B1 8 89 4 15842 77 0.000014 0.0065

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
11771 TP53 tumor protein p53 141 0 110 322 874 110 322 874
8636 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 29 0 50 93 112 50 93 112
7444 NFE2L2 nuclear factor (erythroid-derived 2)-like 2 28 0 32 112 189 32 112 189
12031 TTN titin 329 0 5 12 34 5 12 34
4966 HCN1 hyperpolarization activated cyclic nucleotide-gated potassium channel 1 32 0 5 10 15 5 10 15
2781 CSMD3 CUB and Sushi multiple domains 3 113 0 3 11 32 3 11 32
6422 LRP1B low density lipoprotein-related protein 1B (deleted in tumors) 103 0 3 7 25 3 7 25
3867 FAM135B family with sequence similarity 135, member B 44 0 3 7 15 3 7 15
4991 HEATR7B2 HEAT repeat family member 7B2 30 0 3 5 13 3 5 13
4079 FBXW7 F-box and WD repeat domain containing 7 11 0 3 3 6 3 3 6

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: 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 <2.44e-13
2 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 1.55e-15 2.44e-13
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 1.67e-15 2.44e-13
4 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), EIF2S2(1), MAP3K14(1), NFKB1(2), RELA(3), TP53(144) 2621762 153 140 105 5 10 40 19 34 50 0 2.8e-10 2.11e-15 2.44e-13
5 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 2.78e-15 2.44e-13
6 TIDPATHWAY On ligand binding, interferon gamma receptors stimulate JAK2 kinase to phosphorylate STAT transcription factors, which promote expression of interferon responsive genes. DNAJA3, HSPA1A, IFNG, IFNGR1, IFNGR2, IKBKB, JAK2, LIN7A, NFKB1, NFKBIA, RB1, RELA, TIP-1, TNF, TNFRSF1A, TNFRSF1B, TP53, USH1C, WT1 18 IFNG(1), IFNGR1(4), IFNGR2(1), IKBKB(2), JAK2(4), LIN7A(2), NFKB1(2), RB1(12), RELA(3), TNF(1), TNFRSF1A(2), TNFRSF1B(1), TP53(144), USH1C(7), WT1(4) 4922056 190 143 142 11 18 49 22 43 58 0 6.3e-10 3.00e-15 2.44e-13
7 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 4.22e-15 2.44e-13
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 4.22e-15 2.44e-13
9 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 4.33e-15 2.44e-13
10 TERTPATHWAY hTERC, the RNA subunit of telomerase, and hTERT, the catalytic protein subunit, are required for telomerase activity and are overexpressed in many cancers. HDAC1, MAX, MYC, SP1, SP3, TP53, WT1, ZNF42 7 HDAC1(2), MYC(1), SP1(2), SP3(1), TP53(144), WT1(4) 1887156 154 145 106 9 9 42 20 36 47 0 5.1e-08 4.55e-15 2.44e-13

Table 7.  Get Full Table A Ranked List of Significantly Mutated Genesets (Excluding Significantly Mutated Genes). Number of significant genesets found: 0. Number of genesets displayed: 10

rank geneset description genes N_genes mut_tally N n npat nsite nsil n1 n2 n3 n4 n5 n6 p_ns_s p q
1 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 0.036 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 0.16 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 0.23 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 0.25 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 0.35 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 0.41 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 0.42 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 0.46 1
10 HSA00520_NUCLEOTIDE_SUGARS_METABOLISM Genes involved in nucleotide sugars metabolism GALE, GALT, TGDS, UGDH, UGP2, UXS1 6 GALT(1), TGDS(1), UGDH(2), UGP2(4), UXS1(4) 1320760 12 11 12 1 5 2 0 3 2 0 0.17 0.48 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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