Stomach 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: STAD

  • Number of patients in set: 133

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:STAD.final_analysis_set.maf

  • Significantly mutated genes (q ≤ 0.1): 57

  • Mutations seen in COSMIC: 342

  • Significantly mutated genes in COSMIC territory: 22

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

  • Significantly mutated genesets: 12

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

Mutation Preprocessing

  • Read 133 MAFs of type "Broad"

  • Total number of mutations in input MAFs: 267713

  • After removing 171098 noncoding mutations: 96615

  • After collapsing adjacent/redundant mutations: 77270

Mutation Filtering

  • Number of mutations before filtering: 77270

  • After removing 396 mutations outside gene set: 76874

  • After removing 95 mutations outside category set: 76779

  • After removing 2 "impossible" mutations in

  • gene-patient-category bins of zero coverage: 76777

Results
Breakdown of Mutations by Type

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

type count
Frame_Shift_Del 2059
Frame_Shift_Ins 306
In_Frame_Del 141
In_Frame_Ins 18
Missense_Mutation 49582
Nonsense_Mutation 2293
Nonstop_Mutation 52
Silent 21076
Splice_Site 1222
Translation_Start_Site 30
Total 76779
Breakdown of Mutation Rates by Category Type

Table 2.  Get Full Table A breakdown of mutation rates per category discovered for this individual set.

category n N rate rate_per_mb relative_rate exp_ns_s_ratio
*CpG->T 17232 213212487 0.000081 81 5.7 2.1
*Np(A/C/T)->transit 16836 3086012671 5.5e-06 5.5 0.38 2
*ApG->G 2333 597942472 3.9e-06 3.9 0.27 2.1
transver 13197 3897167630 3.4e-06 3.4 0.24 5
indel+null 6013 3897167630 1.5e-06 1.5 0.11 NaN
double_null 91 3897167630 2.3e-08 0.023 0.0016 NaN
Total 55702 3897167630 0.000014 14 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: STAD.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: *Np(A/C/T)->transit

  • n3 = number of nonsilent mutations of type: *ApG->G

  • n4 = number of nonsilent mutations of type: transver

  • 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: 57. 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 165051 67 62 48 2 21 13 2 10 20 1 <1.00e-15 2.1e-06 2e-07 2e-07 0 <1.00e-15 <1.38e-12
2 ACVR2A activin A receptor, type IIA 210899 18 17 5 0 0 3 0 1 14 0 2.25e-11 0.28 2e-07 0.0024 0 <1.00e-15 <1.38e-12
3 CBWD1 COBW domain containing 1 131067 18 17 3 0 0 2 0 0 16 0 1.36e-12 0.037 2e-07 3.2e-06 0 <1.00e-15 <1.38e-12
4 KRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog 93127 17 17 8 0 0 12 0 5 0 0 <1.00e-15 0.0055 2.6e-06 0.00042 0 <1.00e-15 <1.38e-12
5 TRIM48 tripartite motif-containing 48 84892 14 14 3 0 0 13 0 1 0 0 4.44e-11 0.0032 2e-07 0.88 0 <1.00e-15 <1.38e-12
6 RPL22 ribosomal protein L22 50726 10 10 1 0 0 0 0 0 10 0 2.64e-09 1 2e-07 0.028 0 <1.00e-15 <1.38e-12
7 SFRS12IP1 SFRS12-interacting protein 1 61056 5 5 1 0 0 0 0 0 5 0 0.00062 1 2e-07 0.42 0 <1.00e-15 <1.38e-12
8 SMAP1 stromal membrane-associated GTPase-activating protein 1 178580 5 5 1 2 0 0 0 0 5 0 0.027 1 2e-07 0.3 0 <1.00e-15 <1.38e-12
9 DNAJC15 DnaJ (Hsp40) homolog, subfamily C, member 15 58957 3 3 3 0 1 0 0 1 1 0 0.011 0.4 0.034 0.01 0 <1.00e-15 <1.38e-12
10 ZNF48 zinc finger protein 48 236871 3 3 1 1 0 0 0 0 3 0 0.60 1 4e-07 0.16 0 <1.00e-15 <1.38e-12
11 EFNA2 ephrin-A2 47344 2 2 2 0 1 0 0 0 1 0 0.097 0.38 0.012 0.69 0 <1.00e-15 <1.38e-12
12 NSF N-ethylmaleimide-sensitive factor 163988 2 2 2 3 0 0 1 0 1 0 0.72 0.99 0.00019 0.7 0 <1.00e-15 <1.38e-12
13 HPGDS 82460 2 1 2 0 0 1 0 0 1 0 0.42 0.5 0.0031 0.88 0 <1.00e-15 <1.38e-12
14 PGM5 phosphoglucomutase 5 187631 21 18 7 0 5 14 0 0 2 0 9.50e-11 0.00034 2e-07 1 0.000017 5.54e-14 7.12e-11
15 ARID1A AT rich interactive domain 1A (SWI-like) 773196 28 26 27 2 4 1 0 5 15 3 1.14e-10 0.064 0.18 0.047 0.059 1.81e-10 2.18e-07
16 RHOA ras homolog gene family, member A 79534 8 7 4 0 0 5 0 3 0 0 1.86e-07 0.089 9.2e-06 0.16 0.000078 3.75e-10 4.22e-07
17 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 437042 33 25 19 3 5 20 3 4 1 0 8.78e-08 0.0045 0.0018 0.0075 0.00021 4.65e-10 4.92e-07
18 INO80E 53262 9 9 4 0 1 0 0 1 6 1 2.93e-08 0.51 0.062 0.00092 0.00088 6.53e-10 6.53e-07
19 FGF22 fibroblast growth factor 22 22304 4 4 1 1 0 0 0 0 4 0 0.00011 1 2e-07 0.99 3.4e-06 8.51e-09 8.06e-06
20 OR8H3 olfactory receptor, family 8, subfamily H, member 3 125419 10 10 8 1 0 4 3 3 0 0 2.25e-07 0.1 0.26 0.011 0.017 7.81e-08 0.000070
21 ZNF804B zinc finger protein 804B 540495 23 21 22 1 0 8 0 12 3 0 2.68e-08 0.019 0.26 0.71 0.45 2.30e-07 0.00020
22 CDH1 cadherin 1, type 1, E-cadherin (epithelial) 338076 14 13 14 4 1 5 1 5 2 0 0.00028 0.39 0.0062 0.0012 0.00016 7.75e-07 0.00063
23 TUSC3 tumor suppressor candidate 3 142522 11 11 10 0 5 1 0 5 0 0 5.10e-07 0.078 0.076 0.22 0.093 8.48e-07 0.00066
24 PRRT2 proline-rich transmembrane protein 2 134137 5 5 2 1 0 0 0 1 4 0 0.010 0.93 2e-07 0.21 0.000011 1.88e-06 0.0014
25 PTH2 parathyroid hormone 2 26182 3 3 1 0 0 0 0 3 0 0 0.0019 0.43 0.000023 0.073 0.000077 2.50e-06 0.0018
26 C17orf63 chromosome 17 open reading frame 63 9845 4 4 4 0 2 0 0 1 1 0 2.82e-06 0.16 NaN NaN NaN 2.82e-06 0.0020
27 IAPP islet amyloid polypeptide 36974 4 4 3 0 0 0 0 4 0 0 0.00025 0.47 0.00029 0.98 0.00081 3.30e-06 0.0022
28 IRF2 interferon regulatory factor 2 143858 10 8 10 1 4 0 0 4 1 1 0.00040 0.2 0.004 0.018 0.00051 3.36e-06 0.0022
29 RNF43 ring finger protein 43 289155 16 15 9 2 1 4 0 0 11 0 0.000022 0.42 0.0099 0.12 0.0095 3.48e-06 0.0022
30 HLA-B major histocompatibility complex, class I, B 131490 12 10 12 0 1 3 2 1 3 2 6.39e-07 0.02 0.95 0.13 0.4 4.14e-06 0.0025
31 HLA-A major histocompatibility complex, class I, A 144803 10 9 10 1 0 2 3 3 2 0 0.000023 0.23 0.12 0.0091 0.015 5.34e-06 0.0031
32 SMAD4 SMAD family member 4 226261 9 8 8 1 3 1 0 2 3 0 0.000028 0.32 0.013 0.078 0.013 5.80e-06 0.0033
33 UPF3A UPF3 regulator of nonsense transcripts homolog A (yeast) 148651 7 7 3 2 0 1 0 0 6 0 0.0056 0.96 0.000084 0.01 0.000092 7.93e-06 0.0043
34 CCDC43 coiled-coil domain containing 43 84224 4 4 2 0 0 0 0 1 3 0 0.018 0.85 1.6e-06 0.55 3e-05 8.34e-06 0.0044
35 PHF2 PHD finger protein 2 350230 14 13 5 4 2 1 0 1 10 0 0.011 0.88 7.6e-06 0.34 7e-05 0.000011 0.0058
TP53

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

ACVR2A

Figure S2.  This figure depicts the distribution of mutations and mutation types across the ACVR2A significant gene.

KRAS

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

TRIM48

Figure S4.  This figure depicts the distribution of mutations and mutation types across the TRIM48 significant gene.

RPL22

Figure S5.  This figure depicts the distribution of mutations and mutation types across the RPL22 significant gene.

SMAP1

Figure S6.  This figure depicts the distribution of mutations and mutation types across the SMAP1 significant gene.

DNAJC15

Figure S7.  This figure depicts the distribution of mutations and mutation types across the DNAJC15 significant gene.

ZNF48

Figure S8.  This figure depicts the distribution of mutations and mutation types across the ZNF48 significant gene.

EFNA2

Figure S9.  This figure depicts the distribution of mutations and mutation types across the EFNA2 significant gene.

NSF

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

HPGDS

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

PGM5

Figure S12.  This figure depicts the distribution of mutations and mutation types across the PGM5 significant gene.

ARID1A

Figure S13.  This figure depicts the distribution of mutations and mutation types across the ARID1A significant gene.

RHOA

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

PIK3CA

Figure S15.  This figure depicts the distribution of mutations and mutation types across the PIK3CA significant gene.

INO80E

Figure S16.  This figure depicts the distribution of mutations and mutation types across the INO80E significant gene.

FGF22

Figure S17.  This figure depicts the distribution of mutations and mutation types across the FGF22 significant gene.

OR8H3

Figure S18.  This figure depicts the distribution of mutations and mutation types across the OR8H3 significant gene.

ZNF804B

Figure S19.  This figure depicts the distribution of mutations and mutation types across the ZNF804B significant gene.

CDH1

Figure S20.  This figure depicts the distribution of mutations and mutation types across the CDH1 significant gene.

TUSC3

Figure S21.  This figure depicts the distribution of mutations and mutation types across the TUSC3 significant gene.

PRRT2

Figure S22.  This figure depicts the distribution of mutations and mutation types across the PRRT2 significant gene.

C17orf63

Figure S23.  This figure depicts the distribution of mutations and mutation types across the C17orf63 significant gene.

IRF2

Figure S24.  This figure depicts the distribution of mutations and mutation types across the IRF2 significant gene.

RNF43

Figure S25.  This figure depicts the distribution of mutations and mutation types across the RNF43 significant gene.

HLA-A

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

SMAD4

Figure S27.  This figure depicts the distribution of mutations and mutation types across the SMAD4 significant gene.

UPF3A

Figure S28.  This figure depicts the distribution of mutations and mutation types across the UPF3A significant gene.

CCDC43

Figure S29.  This figure depicts the distribution of mutations and mutation types across the CCDC43 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: 22. Number of genes displayed: 10

rank gene description n cos n_cos N_cos cos_ev p q
1 ACVR2A activin A receptor, type IIA 18 3 14 399 14 7.3e-15 3.3e-11
2 KRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog 17 51 15 6783 100690 1.1e-13 2.5e-10
3 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 33 184 30 24472 10503 3.2e-13 4.7e-10
4 TP53 tumor protein p53 67 308 63 40964 21281 4.2e-13 4.7e-10
5 SMAD4 SMAD family member 4 9 159 8 21147 25 1.3e-09 1.2e-06
6 CDH1 cadherin 1, type 1, E-cadherin (epithelial) 14 184 8 24472 32 4.1e-09 3.1e-06
7 FBXW7 F-box and WD repeat domain containing 7 11 91 6 12103 279 3.2e-08 0.000021
8 ERBB3 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) 21 6 3 798 3 2.4e-07 0.00014
9 PKHD1 polycystic kidney and hepatic disease 1 (autosomal recessive) 20 8 3 1064 3 5.8e-07 0.00029
10 SMAD2 SMAD family member 2 8 10 3 1330 9 1.1e-06 0.00051

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: 12. 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 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(17), CDC25A(2), CDC25B(4), CDC25C(3), CDK2(2), CHEK1(2), MYT1(12), RB1(8), TP53(67), WEE1(1), YWHAH(1) 3508527 119 78 98 12 37 31 5 16 28 2 4.4e-06 <1.00e-15 <1.54e-13
2 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(2), CCND1(1), CDK2(2), CDKN1A(1), CDKN2A(4), CFL1(1), E2F2(2), MDM2(3), NXT1(2), PRB1(2), TP53(67) 1604627 87 72 68 11 27 21 3 12 23 1 0.00016 <1.00e-15 <1.54e-13
3 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 DNAJC3(1), EIF2S1(1), EIF2S2(2), MAP3K14(3), NFKB1(5), RELA(2), TP53(67) 1951817 81 67 62 7 24 16 2 16 22 1 0.00014 <1.00e-15 <1.54e-13
4 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), MAX(1), SP1(3), SP3(3), TP53(67), WT1(1) 1390783 77 67 58 9 24 17 2 11 22 1 0.000094 <1.00e-15 <1.54e-13
5 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(17), ATR(5), CDC25C(3), CHEK1(2), CHEK2(5), TP53(67), YWHAH(1) 3188811 100 77 80 11 32 24 4 13 25 2 0.00047 3.44e-15 4.24e-13
6 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(2), CDKN2A(4), MDM2(3), PIK3CA(33), PIK3R1(7), POLR1A(8), POLR1B(2), POLR1C(2), POLR1D(1), RB1(8), TBX2(4), TP53(67), TWIST1(1) 4003294 142 87 108 24 36 48 6 21 30 1 0.000054 2.83e-14 2.91e-12
7 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 DNAJA3(2), HSPA1A(1), IFNG(2), IFNGR1(2), IFNGR2(1), IKBKB(3), JAK2(8), LIN7A(6), NFKB1(5), RB1(8), RELA(2), TNF(2), TNFRSF1A(3), TNFRSF1B(1), TP53(67), USH1C(1), WT1(1) 3602378 115 75 94 18 30 27 3 24 30 1 0.00043 8.90e-13 7.83e-11
8 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(10), AKT1(2), ATM(17), CDKN1A(1), CPB2(4), CSNK1D(2), FHL2(2), HIC1(1), HIF1A(2), HSPA1A(1), IGFBP3(4), MAPK8(4), MDM2(3), NFKBIB(4), NQO1(3), TP53(67) 4118242 127 84 107 21 40 33 4 19 29 2 0.0002 1.04e-12 8.00e-11
9 ATMPATHWAY The tumor-suppressing protein kinase ATM responds to radiation-induced DNA damage by blocking cell-cycle progression and activating DNA repair. ABL1, ATM, BRCA1, CDKN1A, CHEK1, CHEK2, GADD45A, JUN, MAPK8, MDM2, MRE11A, NBS1, NFKB1, NFKBIA, RAD50, RAD51, RBBP8, RELA, TP53, TP73 19 ABL1(2), ATM(17), BRCA1(9), CDKN1A(1), CHEK1(2), CHEK2(5), JUN(2), MAPK8(4), MDM2(3), MRE11A(2), NFKB1(5), RAD50(6), RAD51(1), RBBP8(4), RELA(2), TP53(67), TP73(5) 5915081 137 83 117 21 36 36 5 26 32 2 0.0004 6.69e-11 4.58e-09
10 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(2), APAF1(2), ATM(17), BAD(1), BCL2(1), BID(1), CASP3(1), CASP6(1), CASP7(2), CASP9(1), CYCS(1), EIF2S1(1), PTK2(7), PXN(2), STAT1(6), TLN1(13), TP53(67) 5433042 126 78 106 18 43 32 7 16 26 2 0.000039 1.03e-10 6.37e-09

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 HSA00472_D_ARGININE_AND_D_ORNITHINE_METABOLISM Genes involved in D-arginine and D-ornithine metabolism DAO 1 DAO(5) 143247 5 5 5 1 1 0 1 1 2 0 0.55 0.019 1
2 TCRMOLECULE T Cell Receptor and CD3 Complex CD3D, CD3E, CD3G, CD3Z, TRA@, TRB@ 3 CD3E(3), CD3G(2) 225536 5 5 4 1 0 2 1 0 2 0 0.68 0.1 1
3 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(3), ERBB4(18), NRG2(5), NRG3(9), PSEN1(1) 1780945 36 27 35 6 8 13 4 7 4 0 0.03 0.19 1
4 SLRPPATHWAY Small leucine-rich proteoglycans (SLRPs) interact with and reorganize collagen fibers in the extracellular matrix. BGN, DCN, DSPG3, FMOD, KERA, LUM 5 BGN(2), DCN(2), FMOD(9), KERA(1), LUM(3) 721456 17 15 17 4 8 3 0 5 1 0 0.29 0.26 1
5 FLUMAZENILPATHWAY Flumazenil is a benzodiazepine receptor antagonist that may induce protective preconditioning in ischemic cardiomyocytes. GABRA1, GABRA2, GABRA3, GABRA4, GABRA5, GABRA6, GPX1, PRKCE, SOD1 9 GABRA1(5), GABRA2(5), GABRA3(5), GABRA4(4), GABRA5(5), GABRA6(5), GPX1(1), PRKCE(6) 1565795 36 24 36 9 13 7 5 10 1 0 0.13 0.28 1
6 UREACYCLEPATHWAY Ammonia released from amino acid deamination is used to produce carbamoyl phosphate, which is used to convert ornithine to citrulline, from which urea is eventually formed. ARG1, ASL, ASS, CPS1, GLS, GLUD1, GOT1 6 ARG1(2), ASL(5), CPS1(15), GLS(4), GLUD1(4), GOT1(2) 1545002 32 25 32 7 9 9 2 10 2 0 0.14 0.38 1
7 EOSINOPHILSPATHWAY Recruitment of eosinophils in the inflammatory response observed in asthma occurs via the chemoattractant eotaxin binding to the CCR3 receptor. CCL11, CCL5, CCR3, CSF2, HLA-DRA, HLA-DRB1, IL3, IL5 8 CCL11(1), CCL5(1), CCR3(4), HLA-DRA(3), HLA-DRB1(1), IL3(1) 602660 11 10 11 3 4 4 0 2 1 0 0.35 0.38 1
8 GABAPATHWAY Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter whose receptor is regulated by Plic-1, gephyrin, and GABARAP, which promote receptor clustering. DNM1, GABARAP, GABRA1, GABRA2, GABRA3, GABRA4, GABRA5, GABRA6, GPHN, NSF, SRC, UBQLN1 11 DNM1(5), GABRA1(5), GABRA2(5), GABRA3(5), GABRA4(4), GABRA5(5), GABRA6(5), GPHN(7), UBQLN1(4) 2211584 45 26 45 9 11 10 6 13 5 0 0.058 0.42 1
9 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(2), IFNG(2), IL12B(2), IL2(1) 592301 7 7 7 1 0 3 1 3 0 0 0.33 0.42 1
10 HSA00660_C5_BRANCHED_DIBASIC_ACID_METABOLISM Genes involved in C5-branched dibasic acid metabolism ILVBL, SUCLA2 2 ILVBL(3), SUCLA2(3) 416247 6 6 6 0 3 0 0 1 2 0 0.19 0.51 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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