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): 92

Mutations seen in COSMIC: 342

Significantly mutated genes in COSMIC territory: 22

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

Significantly mutated genesets: 13

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

Table 3. Get Full Table A Ranked List of Significantly Mutated Genes. Number of significant genes found: 92. 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 | <1.64e-12
2 | ACVR2A | activin A receptor, type IIA | 210899 | 18 | 17 | 5 | 0 | 0 | 3 | 0 | 1 | 14 | 0 | <1.00e-15 | 0.28 | 2e-07 | 0.0024 | 0 | <1.00e-15 | <1.64e-12
3 | CBWD1 | COBW domain containing 1 | 131067 | 18 | 17 | 3 | 0 | 0 | 2 | 0 | 0 | 16 | 0 | <1.00e-15 | 0.037 | 2e-07 | 2.4e-06 | 0 | <1.00e-15 | <1.64e-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 | 2e-06 | 0.00041 | 0 | <1.00e-15 | <1.64e-12
5 | RPL22 | ribosomal protein L22 | 50726 | 10 | 10 | 1 | 0 | 0 | 0 | 0 | 0 | 10 | 0 | 1.29e-12 | 1 | 2e-07 | 0.031 | 0 | <1.00e-15 | <1.64e-12
6 | PRRT2 | proline-rich transmembrane protein 2 | 134137 | 5 | 5 | 2 | 1 | 0 | 0 | 0 | 1 | 4 | 0 | 0.0021 | 0.93 | 2e-07 | 0.21 | 0 | <1.00e-15 | <1.64e-12
7 | SMAP1 | stromal membrane-associated GTPase-activating protein 1 | 178580 | 5 | 5 | 1 | 2 | 0 | 0 | 0 | 0 | 5 | 0 | 0.0088 | 1 | 2e-07 | 0.3 | 0 | <1.00e-15 | <1.64e-12
8 | DNAJC15 | DnaJ (Hsp40) homolog, subfamily C, member 15 | 58957 | 3 | 3 | 3 | 0 | 1 | 0 | 0 | 1 | 1 | 0 | 0.0052 | 0.4 | 0.045 | 0.014 | 0 | <1.00e-15 | <1.64e-12
9 | EFNA2 | ephrin-A2 | 47344 | 2 | 2 | 2 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 0.074 | 0.38 | 0.025 | 0.7 | 0 | <1.00e-15 | <1.64e-12
10 | NSF | N-ethylmaleimide-sensitive factor | 163988 | 2 | 2 | 2 | 3 | 0 | 0 | 1 | 0 | 1 | 0 | 0.62 | 0.99 | 0.00034 | 0.75 | 0 | <1.00e-15 | <1.64e-12
11 | HPGDS |  | 82460 | 2 | 1 | 2 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0.39 | 0.5 | 0.0031 | 0.88 | 0 | <1.00e-15 | <1.64e-12
12 | TRIM48 | tripartite motif-containing 48 | 84892 | 14 | 14 | 3 | 0 | 0 | 13 | 0 | 1 | 0 | 0 | 2.18e-12 | 0.0032 | 2e-07 | 0.91 | 0.000022 | 1.89e-15 | 2.83e-12
13 | PGM5 | phosphoglucomutase 5 | 187631 | 21 | 18 | 7 | 0 | 5 | 14 | 0 | 0 | 2 | 0 | 8.06e-11 | 0.00034 | 2e-07 | 1 | 0.000018 | 5.16e-14 | 7.15e-11
14 | ARID1A | AT rich interactive domain 1A (SWI-like) | 773196 | 28 | 26 | 27 | 2 | 4 | 1 | 0 | 5 | 15 | 3 | 2.94e-14 | 0.064 | 0.78 | 0.23 | 0.46 | 4.41e-13 | 5.67e-10
15 | ZNF804B | zinc finger protein 804B | 540495 | 23 | 21 | 22 | 1 | 0 | 8 | 0 | 12 | 3 | 0 | 3.99e-12 | 0.019 | 0.26 | 0.71 | 0.45 | 5.00e-11 | 5.99e-08
16 | FGF22 | fibroblast growth factor 22 | 22304 | 4 | 4 | 1 | 1 | 0 | 0 | 0 | 0 | 4 | 0 | 0.000015 | 1 | 4e-07 | 1 | 4e-07 | 1.57e-10 | 1.75e-07
17 | PIK3CA | phosphoinositide-3-kinase, catalytic, alpha polypeptide | 437042 | 33 | 25 | 19 | 3 | 5 | 20 | 3 | 4 | 1 | 0 | 7.00e-08 | 0.0045 | 0.0018 | 0.0089 | 0.000088 | 1.65e-10 | 1.75e-07
18 | RHOA | ras homolog gene family, member A | 79534 | 8 | 7 | 4 | 0 | 0 | 5 | 0 | 3 | 0 | 0 | 1.01e-07 | 0.089 | 9.2e-06 | 0.16 | 0.000078 | 2.09e-10 | 2.09e-07
19 | INO80E |  | 53262 | 9 | 9 | 4 | 0 | 1 | 0 | 0 | 1 | 6 | 1 | 1.48e-09 | 0.51 | 0.45 | 0.002 | 0.0082 | 3.19e-10 | 3.02e-07
20 | OR8H3 | olfactory receptor, family 8, subfamily H, member 3 | 125419 | 10 | 10 | 8 | 1 | 0 | 4 | 3 | 3 | 0 | 0 | 2.23e-08 | 0.1 | 0.26 | 0.011 | 0.017 | 8.61e-09 | 7.75e-06
21 | SFRS12IP1 | SFRS12-interacting protein 1 | 61056 | 5 | 5 | 1 | 0 | 0 | 0 | 0 | 0 | 5 | 0 | 0.000079 | 1 | 2e-07 | 0.46 | 0.000017 | 2.93e-08 | 0.000025
22 | RNF43 | ring finger protein 43 | 289155 | 16 | 15 | 9 | 2 | 1 | 4 | 0 | 0 | 11 | 0 | 6.56e-07 | 0.42 | 0.0049 | 0.16 | 0.0075 | 9.92e-08 | 0.000081
23 | PCDH15 | protocadherin 15 | 988063 | 25 | 23 | 25 | 3 | 2 | 5 | 5 | 8 | 5 | 0 | 1.97e-08 | 0.02 | 0.18 | 0.98 | 0.31 | 1.22e-07 | 0.000095
24 | CDH1 | cadherin 1, type 1, E-cadherin (epithelial) | 338076 | 14 | 13 | 14 | 4 | 1 | 5 | 1 | 5 | 2 | 0 | 0.000031 | 0.39 | 0.013 | 0.0025 | 0.00036 | 2.15e-07 | 0.00016
25 | TUSC3 | tumor suppressor candidate 3 | 142522 | 11 | 11 | 10 | 0 | 5 | 1 | 0 | 5 | 0 | 0 | 1.46e-07 | 0.078 | 0.081 | 0.33 | 0.11 | 3.13e-07 | 0.00023
26 | SMAD4 | SMAD family member 4 | 226261 | 9 | 8 | 8 | 1 | 3 | 1 | 0 | 2 | 3 | 0 | 2.15e-06 | 0.32 | 0.013 | 0.073 | 0.0093 | 3.73e-07 | 0.00026
27 | IAPP | islet amyloid polypeptide | 36974 | 4 | 4 | 3 | 0 | 0 | 0 | 0 | 4 | 0 | 0 | 0.000045 | 0.47 | 0.00029 | 0.98 | 0.00073 | 6.06e-07 | 0.00040
28 | PHF2 | PHD finger protein 2 | 350230 | 14 | 13 | 5 | 4 | 2 | 1 | 0 | 1 | 10 | 0 | 0.00034 | 0.88 | 4e-05 | 0.45 | 0.00012 | 7.20e-07 | 0.00046
29 | SPRYD5 | SPRY domain containing 5 | 121763 | 8 | 8 | 6 | 0 | 0 | 0 | 1 | 2 | 5 | 0 | 5.48e-08 | 0.45 | 0.77 | 1 | 1 | 9.71e-07 | 0.00060
30 | IRF2 | interferon regulatory factor 2 | 143858 | 10 | 8 | 10 | 1 | 4 | 0 | 0 | 4 | 1 | 1 | 0.00020 | 0.2 | 0.004 | 0.018 | 0.00051 | 1.77e-06 | 0.0011
31 | C17orf63 | chromosome 17 open reading frame 63 | 9845 | 4 | 4 | 4 | 0 | 2 | 0 | 0 | 1 | 1 | 0 | 2.02e-06 | 0.16 | NaN | NaN | NaN | 2.02e-06 | 0.0012
32 | CCDC43 | coiled-coil domain containing 43 | 84224 | 4 | 4 | 2 | 0 | 0 | 0 | 0 | 1 | 3 | 0 | 0.0053 | 0.85 | 3.4e-06 | 0.59 | 0.000026 | 2.29e-06 | 0.0013
33 | HLA-A | major histocompatibility complex, class I, A | 144803 | 10 | 9 | 10 | 1 | 0 | 2 | 3 | 3 | 2 | 0 | 9.89e-06 | 0.23 | 0.13 | 0.0074 | 0.015 | 2.54e-06 | 0.0014
34 | PTH2 | parathyroid hormone 2 | 26182 | 3 | 3 | 1 | 0 | 0 | 0 | 0 | 3 | 0 | 0 | 0.00029 | 0.43 | 0.000038 | 0.11 | 0.00076 | 3.57e-06 | 0.0019
35 | TLR4 | toll-like receptor 4 | 336693 | 13 | 13 | 11 | 2 | 0 | 2 | 3 | 8 | 0 | 0 | 3.56e-06 | 0.32 | 0.031 | 0.92 | 0.065 | 3.79e-06 | 0.0019

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.

RPL22

Figure S4. This figure depicts the distribution of mutations and mutation types across the RPL22 significant gene.

PRRT2

Figure S5. This figure depicts the distribution of mutations and mutation types across the PRRT2 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.

EFNA2

Figure S8. This figure depicts the distribution of mutations and mutation types across the EFNA2 significant gene.

NSF

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

HPGDS

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

TRIM48

Figure S11. This figure depicts the distribution of mutations and mutation types across the TRIM48 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.

ZNF804B

Figure S14. This figure depicts the distribution of mutations and mutation types across the ZNF804B significant gene.

FGF22

Figure S15. This figure depicts the distribution of mutations and mutation types across the FGF22 significant gene.

PIK3CA

Figure S16. This figure depicts the distribution of mutations and mutation types across the PIK3CA significant gene.

RHOA

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

INO80E

Figure S18. This figure depicts the distribution of mutations and mutation types across the INO80E significant gene.

OR8H3

Figure S19. This figure depicts the distribution of mutations and mutation types across the OR8H3 significant gene.

RNF43

Figure S20. This figure depicts the distribution of mutations and mutation types across the RNF43 significant gene.

PCDH15

Figure S21. This figure depicts the distribution of mutations and mutation types across the PCDH15 significant gene.

CDH1

Figure S22. This figure depicts the distribution of mutations and mutation types across the CDH1 significant gene.

TUSC3

Figure S23. This figure depicts the distribution of mutations and mutation types across the TUSC3 significant gene.

SMAD4

Figure S24. This figure depicts the distribution of mutations and mutation types across the SMAD4 significant gene.

PHF2

Figure S25. This figure depicts the distribution of mutations and mutation types across the PHF2 significant gene.

SPRYD5

Figure S26. This figure depicts the distribution of mutations and mutation types across the SPRYD5 significant gene.

IRF2

Figure S27. This figure depicts the distribution of mutations and mutation types across the IRF2 significant gene.

C17orf63

Figure S28. This figure depicts the distribution of mutations and mutation types across the C17orf63 significant gene.

CCDC43

Figure S29. This figure depicts the distribution of mutations and mutation types across the CCDC43 significant gene.

HLA-A

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

Note:

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 .

null - mutation category that includes nonsense, frameshift, splice-site mutations

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 = p-value (overall)

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

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: 13. 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 | 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 | <1.00e-15 | <8.80e-14
2 | 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 | <1.00e-15 | <8.80e-14
3 | 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 | <8.80e-14
4 | 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 | <1.00e-15 | <8.80e-14
5 | 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 | <8.80e-14
6 | 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 | <8.80e-14
7 | 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 | <8.80e-14
8 | 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 | 1.22e-15 | 9.40e-14
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 | 2.11e-15 | 1.44e-13
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 | 3.95e-13 | 2.43e-11

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 | 0.0039 | 1
2 | 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 | 0.1 | 1
3 | 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 | 0.11 | 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 | 0.13 | 1
5 | 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 | 0.18 | 1
6 | 1_AND_2_METHYLNAPHTHALENE_DEGRADATION |  | ADH1A, ADH1A, ADH1B, ADH1C, ADH1B, ADH1C, ADH4, ADH6, ADH7, ADHFE1 | 7 | ADH1A(4), ADH1B(1), ADH1C(3), ADH4(2), ADH6(4), ADH7(2), ADHFE1(6) | 1120150 | 22 | 17 | 21 | 5 | 2 | 9 | 0 | 6 | 5 | 0 | 0.26 | 0.19 | 1
7 | 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 | 0.23 | 1
8 | 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 | 0.27 | 1
9 | TOB1PATHWAY | TGF-beta signaling activates SMADs, which interact with intracellular Tob to maintain unstimulated T cells by repressing IL-2 expression. | CD28, CD3D, CD3E, CD3G, CD3Z, IFNG, IL2, IL2RA, IL4, MADH3, MADH4, TGFB1, TGFB2, TGFB3, TGFBR1, TGFBR2, TGFBR3, TOB1, TOB2, TRA@, TRB@ | 16 | CD3E(3), CD3G(2), IFNG(2), IL2(1), IL2RA(1), TGFB1(3), TGFB2(6), TGFB3(4), TGFBR1(2), TGFBR2(6), TGFBR3(2), TOB1(1), TOB2(5) | 2099747 | 38 | 26 | 37 | 9 | 6 | 15 | 3 | 10 | 4 | 0 | 0.21 | 0.3 | 1
10 | HSA00641_3_CHLOROACRYLIC_ACID_DEGRADATION | Genes involved in 3-chloroacrylic acid degradation | ADH1A, ADH1B, ADH1C, ADH4, ADH5, ADH6, ADH7, ADHFE1, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH7A1, ALDH9A1 | 15 | ADH1A(4), ADH1B(1), ADH1C(3), ADH4(2), ADH5(1), ADH6(4), ADH7(2), ADHFE1(6), ALDH1A3(6), ALDH1B1(3), ALDH2(1), ALDH3A1(5), ALDH3A2(5), ALDH9A1(4) | 2628366 | 47 | 29 | 46 | 9 | 7 | 15 | 0 | 16 | 9 | 0 | 0.047 | 0.33 | 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.

- Analysis Results (MD5 checksum)

- Auxiliary Data (MD5 checksum)

- MAGE-TAB File (MD5 checksum)

References
[1] TCGA, Integrated genomic analyses of ovarian carcinoma, Nature 474:609 - 615 (2011)
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