Rectum Adenocarcinoma: Mutation Analysis (MutSig v2.0)
Maintained by Dan DiCara (Broad Institute)
Overview
Introduction

This report serves to describe the mutational landscape and properties of a given individual set, as well as rank genes and genesets according to mutational significance. MutSig v2.0 was used to generate the results found in this report.

- Working with individual set: READ-TP

- Number of patients in set: 69

Input

The input for this pipeline is a set of individuals with the following files associated for each:

1. An annotated .maf file describing the mutations called for the respective individual, and their properties.

2. A .wig file that contains information about the coverage of the sample.

Summary

- MAF used for this analysis:READ-TP.final_analysis_set.maf

- Significantly mutated genes (q ≤ 0.1): 17

- Mutations seen in COSMIC: 222

- Significantly mutated genes in COSMIC territory: 10

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

- Significantly mutated genesets: 111

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

Mutation Preprocessing

- Read 38 MAFs of type "Broad"

- Read 35 MAFs of type "Baylor"

- Total number of mutations in input MAFs: 29413

- After removing 257 invalidated mutations: 29156

- After removing 200 noncoding mutations: 28956

- After collapsing adjacent/redundant mutations: 21678

Mutation Filtering

- Number of mutations before filtering: 21678

- After removing 200 mutations outside gene set: 21478

- After removing 172 mutations outside category set: 21306

- After removing 2 "impossible" mutations in

- gene-patient-category bins of zero coverage: 21304

Results
Breakdown of Mutations by Type

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

type | count
--- | ---
De_novo_Start_InFrame | 4
De_novo_Start_OutOfFrame | 30
Frame_Shift_Del | 151
Frame_Shift_Ins | 155
In_Frame_Del | 27
In_Frame_Ins | 7
Missense_Mutation | 14471
Nonsense_Mutation | 1779
Nonstop_Mutation | 6
Read-through | 10
Silent | 4628
Splice_Site | 38
Total | 21306

Breakdown of Mutation Rates by Category Type

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

category | n | N | rate | rate_per_mb | relative_rate
--- | --- | --- | --- | --- | ---
*CpG->T | 4919 | 99673101 | 0.000049 | 49 | 5.4
*Cp(A/C/T)->mut | 6672 | 832257993 | 8e-06 | 8 | 0.88
A->mut | 2743 | 908854391 | 3e-06 | 3 | 0.33
*CpG->(G/A) | 135 | 99673101 | 1.4e-06 | 1.4 | 0.15
indel+null | 2051 | 1840785523 | 1.1e-06 | 1.1 | 0.12
double_null | 157 | 1840785523 | 8.5e-08 | 0.085 | 0.0094
Total | 16677 | 1840785523 | 9.1e-06 | 9.1 | 1

Target Coverage for Each Individual

The x axis represents the samples. The y axis represents the exons, one row per exon, and they are sorted by average coverage across samples. For exons with exactly the same average coverage, they are sorted next by the %GC of the exon. (The secondary sort is especially useful for the zero-coverage exons at the bottom).

Figure 1.

Distribution of Mutation Counts, Coverage, and Mutation Rates Across Samples

Figure 2. Patients counts and rates file used to generate this plot: READ-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: *CpG->T

- n2 = number of nonsilent mutations of type: *Cp(A/C/T)->mut

- n3 = number of nonsilent mutations of type: A->mut

- n4 = number of nonsilent mutations of type: *CpG->(G/A)

- n5 = number of nonsilent mutations of type: indel+null

- n6 = number of nonsilent mutations of type: double_null

- p_classic = p-value for the observed amount of nonsilent mutations being elevated in this gene

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

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

- p_joint = p-value for clustering + conservation

- p = p-value (overall)

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

Table 3. Get Full Table A Ranked List of Significantly Mutated Genes. Number of significant genes found: 17. Number of genes displayed: 35. Click on a gene name to display its stick figure depicting the distribution of mutations and mutation types across the chosen gene (this feature may not be available for all significant genes).

rank | gene | description | N | n | npat | nsite | nsil | n1 | n2 | n3 | n4 | n5 | n6 | p_classic | p_ks | p_cons | p_joint | p | q
--- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | ---
1 | APC | adenomatous polyposis coli | 576224 | 66 | 57 | 56 | 0 | 1 | 4 | 4 | 0 | 39 | 18 | 2.89e-15 | 2e-07 | 0.9 | 0.000022 | 0.000 | 0.000
2 | TP53 | tumor protein p53 | 79667 | 45 | 45 | 30 | 1 | 19 | 6 | 6 | 2 | 12 | 0 | <1.00e-15 | 2e-07 | 2e-07 | 0 | <1.00e-15 | <4.48e-12
3 | KRAS | v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog | 48604 | 38 | 38 | 8 | 0 | 0 | 36 | 1 | 0 | 1 | 0 | 2.78e-15 | 2e-07 | 0.00045 | 0 | <1.00e-15 | <4.48e-12
4 | MUTYH | mutY homolog (E. coli) | 105937 | 2 | 2 | 2 | 2 | 1 | 0 | 0 | 0 | 1 | 0 | 0.0433 | 0.25 | 0.022 | 0 | <1.00e-15 | <4.48e-12
5 | SMAD4 | SMAD family member 4 | 115264 | 8 | 8 | 6 | 0 | 2 | 3 | 3 | 0 | 0 | 0 | 8.09e-11 | 0.16 | 0.14 | 0.14 | 2.86e-10 | 1.02e-06
6 | KIAA1804 |  | 162266 | 11 | 9 | 9 | 0 | 7 | 3 | 1 | 0 | 0 | 0 | 1.25e-08 | 0.025 | 0.011 | 0.011 | 3.13e-09 | 9.35e-06
7 | FBXW7 | F-box and WD repeat domain containing 7 | 177744 | 12 | 9 | 10 | 0 | 6 | 2 | 2 | 0 | 2 | 0 | 1.94e-08 | 0.072 | 0.059 | 0.058 | 2.44e-08 | 6.24e-05
8 | NRAS | neuroblastoma RAS viral (v-ras) oncogene homolog | 40433 | 5 | 5 | 4 | 0 | 0 | 3 | 2 | 0 | 0 | 0 | 1.06e-07 | 0.012 | 0.42 | 0.023 | 5.09e-08 | 0.000114
9 | TCF7L2 | transcription factor 7-like 2 (T-cell specific, HMG-box) | 119026 | 7 | 7 | 7 | 1 | 2 | 3 | 0 | 0 | 2 | 0 | 1.00e-07 | 0.061 | 0.033 | 0.032 | 6.63e-08 | 0.000132
10 | PIK3CA | phosphoinositide-3-kinase, catalytic, alpha polypeptide | 194975 | 7 | 7 | 7 | 1 | 1 | 3 | 3 | 0 | 0 | 0 | 2.12e-07 | 0.12 | 0.39 | 0.15 | 5.93e-07 | 0.00106
11 | OPCML | opioid binding protein/cell adhesion molecule-like | 73709 | 6 | 6 | 6 | 1 | 1 | 3 | 0 | 0 | 2 | 0 | 2.84e-07 | 0.47 | 0.47 | 0.55 | 2.60e-06 | 0.00423
12 | SMAD2 | SMAD family member 2 | 98964 | 5 | 5 | 5 | 0 | 0 | 3 | 1 | 0 | 1 | 0 | 2.16e-05 | 0.012 | 0.3 | 0.018 | 5.98e-06 | 0.00893
13 | SPATA8 | spermatogenesis associated 8 | 20140 | 3 | 3 | 3 | 0 | 0 | 0 | 3 | 0 | 0 | 0 | 4.18e-06 | 0.098 | 0.48 | 0.14 | 8.72e-06 | 0.0120
14 | KRTAP5-5 | keratin associated protein 5-5 | 34487 | 2 | 2 | 1 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 2.10e-05 | 0.08 | 0.0072 | 0.046 | 1.42e-05 | 0.0182
15 | ERBB2 | v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian) | 227547 | 4 | 4 | 2 | 1 | 4 | 0 | 0 | 0 | 0 | 0 | 0.0238 | 9e-05 | 0.021 | 0.000056 | 1.94e-05 | 0.0232
16 | MARCKSL1 | MARCKS-like 1 | 28945 | 2 | 2 | 1 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0.00104 | 0.0017 | 0.17 | 0.0032 | 4.54e-05 | 0.0504
17 | IL1RAPL2 | interleukin 1 receptor accessory protein-like 2 | 139823 | 5 | 5 | 4 | 2 | 2 | 1 | 0 | 0 | 2 | 0 | 2.19e-05 | 0.12 | 0.99 | 0.16 | 4.79e-05 | 0.0504
18 | FAM123B | family with sequence similarity 123B | 190503 | 8 | 6 | 8 | 1 | 0 | 2 | 1 | 0 | 5 | 0 | 8.10e-05 | 0.043 | 0.65 | 0.098 | 0.000101 | 0.101
19 | ZIM3 | zinc finger, imprinted 3 | 98103 | 6 | 5 | 6 | 0 | 1 | 1 | 3 | 0 | 1 | 0 | 6.02e-05 | 0.44 | 0.096 | 0.25 | 0.000184 | 0.173
20 | CACNG7 | calcium channel, voltage-dependent, gamma subunit 7 | 49136 | 3 | 3 | 3 | 0 | 2 | 0 | 0 | 1 | 0 | 0 | 0.000571 | 0.49 | 0.0035 | 0.03 | 0.000208 | 0.184
21 | SGCB | sarcoglycan, beta (43kDa dystrophin-associated glycoprotein) | 64145 | 4 | 4 | 4 | 0 | 0 | 3 | 0 | 0 | 0 | 1 | 4.59e-05 | 0.28 | 0.67 | 0.4 | 0.000216 | 0.184
22 | OSBPL6 | oxysterol binding protein-like 6 | 208053 | 5 | 5 | 5 | 0 | 1 | 2 | 0 | 2 | 0 | 0 | 0.000295 | 0.22 | 0.059 | 0.076 | 0.000263 | 0.205
23 | CSMD1 | CUB and Sushi multiple domains 1 | 392008 | 12 | 9 | 12 | 2 | 4 | 4 | 2 | 0 | 1 | 1 | 2.40e-05 | 0.91 | 0.69 | 1 | 0.000279 | 0.205
24 | TLL2 | tolloid-like 2 | 209091 | 3 | 3 | 2 | 2 | 2 | 0 | 1 | 0 | 0 | 0 | 0.0893 | 0.00014 | 0.18 | 0.00027 | 0.000280 | 0.205
25 | PIK3R1 | phosphoinositide-3-kinase, regulatory subunit 1 (alpha) | 152490 | 5 | 4 | 5 | 0 | 2 | 0 | 0 | 0 | 1 | 2 | 0.000519 | 0.023 | 0.58 | 0.047 | 0.000286 | 0.205
26 | EPYC | epiphycan | 67872 | 4 | 3 | 4 | 0 | 1 | 1 | 1 | 1 | 0 | 0 | 0.000599 | 0.033 | 0.45 | 0.047 | 0.000324 | 0.223
27 | LPHN3 | latrophilin 3 | 147364 | 7 | 6 | 7 | 3 | 3 | 3 | 1 | 0 | 0 | 0 | 5.89e-05 | 0.53 | 0.32 | 0.51 | 0.000341 | 0.224
28 | HHEX | hematopoietically expressed homeobox | 26916 | 2 | 2 | 2 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0.0281 | 0.0025 | 0.35 | 0.0011 | 0.000357 | 0.224
29 | FAT4 | FAT tumor suppressor homolog 4 (Drosophila) | 968552 | 17 | 10 | 17 | 5 | 5 | 8 | 3 | 0 | 1 | 0 | 0.000429 | 0.036 | 0.45 | 0.078 | 0.000377 | 0.224
30 | LIFR | leukemia inhibitory factor receptor alpha | 228178 | 5 | 5 | 5 | 2 | 0 | 2 | 1 | 1 | 1 | 0 | 0.000359 | 0.22 | 0.048 | 0.095 | 0.000383 | 0.224
31 | LRRTM2 | leucine rich repeat transmembrane neuronal 2 | 59242 | 5 | 4 | 5 | 1 | 1 | 1 | 2 | 1 | 0 | 0 | 3.53e-05 | 0.99 | 0.79 | 1 | 0.000397 | 0.224
32 | REEP2 | receptor accessory protein 2 | 49670 | 2 | 2 | 2 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0.0178 | 0.51 | 0.0015 | 0.002 | 0.000401 | 0.224
33 | ZNF395 | zinc finger protein 395 | 89410 | 2 | 2 | 1 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0.0334 | 0.00066 | 0.77 | 0.0012 | 0.000429 | 0.233
34 | CCBP2 | chemokine binding protein 2 | 79700 | 5 | 5 | 5 | 0 | 1 | 2 | 2 | 0 | 0 | 0 | 5.02e-05 | 0.77 | 0.3 | 0.8 | 0.000444 | 0.234
35 | CASP14 | caspase 14, apoptosis-related cysteine peptidase | 51900 | 5 | 4 | 4 | 0 | 4 | 1 | 0 | 0 | 0 | 0 | 0.000185 | 0.14 | 0.68 | 0.24 | 0.000491 | 0.249

COSMIC analyses

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

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

rank | gene | description | n | cos | n_cos | N_cos | cos_ev | p | q
--- | --- | --- | --- | --- | --- | --- | --- | --- | ---
1 | KRAS | v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog | 38 | 51 | 37 | 3519 | 363199 | 1.6e-13 | 7.1e-10
2 | TP53 | tumor protein p53 | 45 | 823 | 45 | 56787 | 17987 | 1.6e-12 | 2.4e-09
3 | APC | adenomatous polyposis coli | 66 | 838 | 50 | 57822 | 1039 | 1.6e-12 | 2.4e-09
4 | NRAS | neuroblastoma RAS viral (v-ras) oncogene homolog | 5 | 28 | 5 | 1932 | 5755 | 1.4e-11 | 1.5e-08
5 | FBXW7 | F-box and WD repeat domain containing 7 | 12 | 91 | 6 | 6279 | 329 | 4.5e-11 | 4.1e-08
6 | SMAD4 | SMAD family member 4 | 8 | 159 | 6 | 10971 | 39 | 1.2e-09 | 9.2e-07
7 | KRTAP5-5 | keratin associated protein 5-5 | 2 | 1 | 2 | 69 | 2 | 1.9e-07 | 0.00012
8 | ERBB2 | v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian) | 4 | 41 | 3 | 2829 | 6 | 2.7e-06 | 0.0016
9 | PIK3CA | phosphoinositide-3-kinase, catalytic, alpha polypeptide | 7 | 184 | 4 | 12696 | 1382 | 6.7e-06 | 0.0033
10 | LRP1B | low density lipoprotein-related protein 1B (deleted in tumors) | 20 | 18 | 2 | 1242 | 2 | 0.000063 | 0.028

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
--- | --- | --- | --- | --- | --- | --- | --- | --- | --- | ---
3872 | KRAS | v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog | 38 | 0 | 278 | 416 | 445 | 278 | 416 | 445
7547 | TP53 | tumor protein p53 | 45 | 0 | 37 | 61 | 105 | 37 | 61 | 105
392 | APC | adenomatous polyposis coli | 66 | 0 | 11 | 21 | 47 | 11 | 21 | 47
2614 | FBXW7 | F-box and WD repeat domain containing 7 | 12 | 0 | 6 | 6 | 6 | 6 | 6 | 6
4875 | NRAS | neuroblastoma RAS viral (v-ras) oncogene homolog | 5 | 0 | 6 | 6 | 6 | 6 | 6 | 6
6841 | SMAD4 | SMAD family member 4 | 8 | 0 | 4 | 4 | 6 | 4 | 4 | 6
2361 | ERBB2 | v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian) | 4 | 0 | 3 | 3 | 3 | 3 | 3 | 3
3782 | KIAA1804 |  | 11 | 0 | 2 | 6 | 7 | 2 | 6 | 7
3465 | IL1RAPL2 | interleukin 1 receptor accessory protein-like 2 | 5 | 0 | 1 | 3 | 3 | 1 | 3 | 3
2083 | DNAH5 | dynein, axonemal, heavy chain 5 | 19 | 0 | 1 | 2 | 2 | 1 | 2 | 2

Note:

n - number of mutations in this gene in the individual set.

mindist - distance (in aa) between closest pair of mutations in this gene

npairs3 - how many pairs of mutations are within 3 aa of each other.

npairs12 - how many pairs of mutations are within 12 aa of each other.

Geneset Analyses

Table 6. Get Full Table A Ranked List of Significantly Mutated Genesets. (Source: MSigDB GSEA Cannonical Pathway Set).Number of significant genesets found: 111. Number of genesets displayed: 10

rank | geneset | description | genes | N_genes | mut_tally | N | n | npat | nsite | nsil | n1 | n2 | n3 | n4 | n5 | n6 | p | q
--- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | ---
1 | ST_GRANULE_CELL_SURVIVAL_PATHWAY | The survival and differentiation of granule cells in the brain is controlled by pro-growth PACAP and pro-apoptotic ceramides. | ADPRT, APC, ASAH1, CAMP, CASP3, CERK, CREB1, CREB3, CREB5, CXCL2, DAG1, EPHB2, FOS, GNAQ, IL8RB, ITPKA, ITPKB, JUN, MAP2K4, MAP2K7, MAPK1, MAPK10, MAPK8, MAPK8IP1, MAPK8IP2, MAPK8IP3, MAPK9, PACAP | 25 | APC(66), CASP3(1), CREB3(1), CREB5(2), DAG1(1), EPHB2(1), FOS(1), GNAQ(1), MAP2K4(2), MAPK10(4), MAPK8(5), MAPK8IP3(1), MAPK9(2) | 2754563 | 88 | 58 | 78 | 3 | 7 | 9 | 7 | 2 | 45 | 18 | <1.00e-15 | <8.74e-14
2 | ST_MYOCYTE_AD_PATHWAY | Cardiac myocytes have a variety of adrenergic receptors that induce subtype-specific signaling effects. | ADRB1, AKT1, APC, ASAH1, BF, CAMP, CAV3, DAG1, DLG4, EPHB2, GAS, GNAI1, GNAQ, HTATIP, ITPR1, ITPR2, ITPR3, KCNJ3, KCNJ5, KCNJ9, MAPK1, PITX2, PLB, PTX1, PTX3, RAC1, RHO, RYR1 | 23 | ADRB1(1), APC(66), CAV3(1), DAG1(1), DLG4(1), EPHB2(1), GNAI1(1), GNAQ(1), ITPR1(8), ITPR2(6), ITPR3(1), KCNJ5(1), KCNJ9(1), RHO(1), RYR1(6) | 4224359 | 97 | 57 | 87 | 9 | 14 | 15 | 6 | 0 | 43 | 19 | <1.00e-15 | <8.74e-14
3 | TGFBPATHWAY | The TGF-beta receptor responds to ligand binding by activating the SMAD family of transcriptional regulations, commonly blocking cell growth. | APC, CDH1, CREBBP, EP300, MADH2, MADH3, MADH4, MADH7, MADHIP, MAP2K1, MAP3K7, MAP3K7IP1, MAPK3, SKIL, TGFB1, TGFB2, TGFB3, TGFBR1, TGFBR2 | 13 | APC(66), CDH1(1), CREBBP(4), EP300(2), MAP2K1(1), MAP3K7(2), MAPK3(1), SKIL(1), TGFB2(4), TGFBR1(3) | 2554178 | 85 | 57 | 75 | 4 | 5 | 10 | 8 | 0 | 44 | 18 | <1.00e-15 | <8.74e-14
4 | HSA04370_VEGF_SIGNALING_PATHWAY | Genes involved in VEGF signaling pathway | AKT1, AKT2, AKT3, BAD, CASP9, CDC42, CHP, HRAS, KDR, KRAS, MAP2K1, MAP2K2, MAPK1, MAPK11, MAPK12, MAPK13, MAPK14, MAPK3, MAPKAPK2, MAPKAPK3, NFAT5, NFATC1, NFATC2, NFATC3, NFATC4, NOS3, NRAS, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PLA2G10, PLA2G12A, PLA2G12B, PLA2G1B, PLA2G2A, PLA2G2D, PLA2G2E, PLA2G2F, PLA2G3, PLA2G4A, PLA2G5, PLA2G6, PLCG1, PLCG2, PPP3CA, PPP3CB, PPP3CC, PPP3R1, PPP3R2, PRKCA, PRKCB1, PRKCG, PTGS2, PTK2, PXN, RAC1, RAC2, RAC3, RAF1, SH2D2A, SHC2, SPHK1, SPHK2, SRC, VEGFA | 69 | AKT2(1), AKT3(1), CDC42(1), KDR(2), KRAS(38), MAP2K1(1), MAP2K2(1), MAPK13(1), MAPK3(1), NFATC1(1), NFATC2(2), NFATC3(1), NFATC4(1), NRAS(5), PIK3CA(7), PIK3CD(1), PIK3CG(2), PIK3R1(5), PIK3R3(4), PLA2G4A(3), PLA2G6(2), PLCG2(4), PPP3CA(2), PPP3CB(1), PPP3CC(1), PRKCA(2), PRKCG(2), PTGS2(1), RAF1(2), SH2D2A(1), SHC2(1), SPHK1(1) | 6915053 | 99 | 50 | 68 | 19 | 27 | 50 | 10 | 0 | 10 | 2 | <1.00e-15 | <8.74e-14
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(4), DAXX(1), PAX3(2), PML(1), RB1(3), SIRT1(1), TP53(45) | 1828212 | 57 | 49 | 42 | 5 | 26 | 7 | 8 | 2 | 14 | 0 | <1.00e-15 | <8.74e-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 | CHUK(2), MAP3K14(1), NFKB1(3), TP53(45) | 924291 | 51 | 47 | 36 | 3 | 22 | 7 | 8 | 2 | 12 | 0 | 1.11e-15 | 8.74e-14
7 | G1_TO_S_CELL_CYCLE_REACTOME |  | ATM, CCNA1, CCNB1, CCND1, CCND2, CCND3, CCNE1, CCNE2, CCNG2, CCNH, CDC25A, CDC45L, CDK2, CDK4, CDK7, CDKN1A, CDKN1B, CDKN1C, CDKN2A, CDKN2B, CDKN2C, CDKN2D, CREB3, CREB3L1, CREB3L3, CREB3L4, CREBL1, CREBL1, TNXB, E2F1, E2F2, E2F3, E2F4, E2F5, E2F6, FLJ14001, GADD45A, GBA2, MCM2, MCM3, MCM4, MCM5, MCM6, MCM7, MDM2, MNAT1, MYC, MYT1, NACA, NACA, FKSG17, ORC1L, ORC2L, ORC3L, ORC4L, ORC5L, ORC6L, PCNA, POLA2, POLE, POLE2, PRIM1, PRIM2A, RB1, RBL1, RPA1, RPA2, RPA3, TFDP1, TFDP2, TP53, WEE1 | 63 | ATM(10), CCNA1(2), CCNE2(1), CDK4(1), CDKN1B(2), CREB3(1), CREB3L3(2), E2F3(1), MCM3(2), MCM5(3), MCM6(1), MCM7(1), MYT1(5), PCNA(1), POLE(4), POLE2(1), RB1(3), RBL1(2), TNXB(3), TP53(45) | 7068990 | 91 | 53 | 75 | 16 | 31 | 25 | 12 | 3 | 19 | 1 | 1.22e-15 | 8.74e-14
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 | 18 | ABCB1(5), ATM(10), CPB2(1), CSNK1D(1), FHL2(1), HIF1A(2), IGFBP3(2), MAPK8(5), TP53(45) | 2001688 | 72 | 50 | 57 | 4 | 26 | 18 | 9 | 3 | 15 | 1 | 1.33e-15 | 8.74e-14
9 | WNTPATHWAY | The Wnt glycoprotein binds to membrane-bound receptors such as Frizzled to activate a number of signaling pathways, including that of beta-catenin. | APC, AXIN1, BTRC, CCND1, CREBBP, CSNK1A1, CSNK1D, CSNK2A1, CTBP1, CTNNB1, DVL1, FRAT1, FZD1, GSK3B, HDAC1, MADH4, MAP3K7, MAP3K7IP1, MYC, NLK, PPARD, PPP2CA, TCF1, TLE1, WIF1, WNT1 | 21 | APC(66), AXIN1(1), BTRC(3), CREBBP(4), CSNK1D(1), CTNNB1(4), FZD1(1), GSK3B(1), MAP3K7(2), PPARD(1) | 2701685 | 84 | 58 | 74 | 4 | 8 | 9 | 8 | 0 | 41 | 18 | 1.44e-15 | 8.74e-14
10 | P53PATHWAY | p53 induces cell cycle arrest or apoptosis under conditions of DNA damage. | APAF1, ATM, BAX, BCL2, CCND1, CCNE1, CDK2, CDK4, CDKN1A, E2F1, GADD45A, MDM2, PCNA, RB1, TIMP3, TP53 | 16 | APAF1(1), ATM(10), CDK4(1), PCNA(1), RB1(3), TIMP3(1), TP53(45) | 1820960 | 62 | 50 | 47 | 6 | 21 | 14 | 9 | 2 | 15 | 1 | 1.67e-15 | 8.74e-14

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

rank | geneset | description | genes | N_genes | mut_tally | N | n | npat | nsite | nsil | n1 | n2 | n3 | n4 | n5 | n6 | p | q
--- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | ---
1 | C21_STEROID_HORMONE_METABOLISM |  | AKR1C4, AKR1D1, CYP11A1, CYP11B1, CYP11B2, CYP17A1, CYP21A2, HSD11B1, HSD11B2, HSD3B1, HSD3B2 | 11 | AKR1C4(1), AKR1D1(1), CYP11A1(2), CYP11B1(4), CYP21A2(1), HSD3B1(1), HSD3B2(1) | 837086 | 11 | 10 | 11 | 2 | 3 | 5 | 1 | 0 | 2 | 0 | 0.0014 | 0.3
2 | HSA00140_C21_STEROID_HORMONE_METABOLISM | Genes involved in C21-steroid hormone metabolism | AKR1C4, AKR1D1, CYP11A1, CYP11B1, CYP11B2, CYP17A1, CYP21A2, HSD11B1, HSD11B2, HSD3B1, HSD3B2 | 11 | AKR1C4(1), AKR1D1(1), CYP11A1(2), CYP11B1(4), CYP21A2(1), HSD3B1(1), HSD3B2(1) | 837086 | 11 | 10 | 11 | 2 | 3 | 5 | 1 | 0 | 2 | 0 | 0.0014 | 0.3
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(1), ERBB4(5), NRG2(2), NRG3(4), PRKCA(2) | 908762 | 14 | 9 | 14 | 1 | 4 | 5 | 1 | 1 | 3 | 0 | 0.0014 | 0.3
4 | HCMVPATHWAY | Cytomegalovirus activates MAP kinase pathways in the host cell, inducing transcription of viral genes. | AKT1, CREB1, MAP2K1, MAP2K2, MAP2K3, MAP2K6, MAP3K1, MAPK1, MAPK14, MAPK3, NFKB1, PIK3CA, PIK3R1, RB1, RELA, SP1 | 15 | MAP2K1(1), MAP2K2(1), MAP2K3(4), MAP2K6(1), MAP3K1(2), MAPK3(1), NFKB1(3), PIK3R1(5), RB1(3) | 1720824 | 21 | 10 | 21 | 3 | 7 | 4 | 4 | 1 | 3 | 2 | 0.004 | 0.54
5 | HSA00240_PYRIMIDINE_METABOLISM | Genes involved in pyrimidine metabolism | AICDA, AK3, CAD, CANT1, CDA, CMPK, CTPS, CTPS2, DCK, DCTD, DHODH, DPYD, DPYS, DTYMK, DUT, ECGF1, ENTPD1, ENTPD3, ENTPD4, ENTPD5, ENTPD6, ENTPD8, ITPA, NME1, NME2, NME4, NME6, NME7, NP, NT5C, NT5C1A, NT5C1B, NT5C2, NT5C3, NT5E, NT5M, NUDT2, PNPT1, POLA1, POLA2, POLD1, POLD2, POLD3, POLD4, POLE, POLE2, POLE3, POLE4, POLR1A, POLR1B, POLR1C, POLR1D, POLR2A, POLR2B, POLR2C, POLR2D, POLR2E, POLR2F, POLR2G, POLR2H, POLR2I, POLR2J, POLR2K, POLR2L, POLR3A, POLR3B, POLR3G, POLR3GL, POLR3H, POLR3K, PRIM1, PRIM2, RFC5, RRM1, RRM2, RRM2B, TK1, TK2, TXNRD1, TXNRD2, TYMS, UCK1, UCK2, UMPS, UPB1, UPP1, UPP2, UPRT, ZNRD1 | 86 | AICDA(1), CAD(1), CTPS(1), DCK(1), DHODH(1), DPYD(6), DPYS(1), DTYMK(1), ENTPD5(1), ENTPD6(1), NME6(1), NME7(2), NT5C1B(1), NT5C2(1), NT5E(1), PNPT1(5), POLA1(3), POLE(4), POLE2(1), POLR1A(3), POLR1B(2), POLR2B(3), POLR2K(1), POLR3A(4), POLR3B(5), POLR3K(1), PRIM2(3), RFC5(1), RRM1(1), TK2(1), TXNRD1(1), TXNRD2(1), TYMS(1), UMPS(1), UPB1(2), UPP2(1), UPRT(1) | 7933506 | 67 | 28 | 65 | 15 | 18 | 26 | 10 | 0 | 13 | 0 | 0.0046 | 0.54
6 | CREMPATHWAY | The transcription factor CREM activates a post-meiotic transcriptional cascade culminating in spermatogenesis. | ADCY1, CREM, FHL5, FSHB, FSHR, GNAS, XPO1 | 7 | ADCY1(4), FHL5(3), FSHB(1), FSHR(1), XPO1(1) | 917313 | 10 | 9 | 10 | 4 | 4 | 1 | 3 | 1 | 1 | 0 | 0.0053 | 0.54
7 | GSPATHWAY | Activated G-protein coupled receptors stimulate cAMP production and thus activate protein kinase A, involved in a number of signal transduction pathways. | ADCY1, GNAS, GNB1, GNGT1, PRKACA, PRKAR1A | 6 | ADCY1(4), GNGT1(1), PRKACA(1), PRKAR1A(4) | 607553 | 10 | 8 | 10 | 1 | 3 | 4 | 1 | 0 | 2 | 0 | 0.0071 | 0.62
8 | PAR1PATHWAY | Activated extracellular thrombin cleaves and activates the G-protein coupled receptors PAR1 and PAR4, which activate platelets. | ADCY1, ARHA, ARHGEF1, F2, F2R, F2RL3, GNA12, GNA13, GNAI1, GNAQ, GNB1, GNGT1, MAP3K7, PIK3CA, PIK3R1, PLCB1, PPP1R12B, PRKCA, PRKCB1, PTK2B, ROCK1 | 18 | ADCY1(4), ARHGEF1(1), F2(1), GNAI1(1), GNAQ(1), GNGT1(1), MAP3K7(2), PIK3R1(5), PPP1R12B(4), PRKCA(2), ROCK1(7) | 2322908 | 29 | 13 | 29 | 7 | 8 | 7 | 5 | 0 | 7 | 2 | 0.008 | 0.62
9 | NEUROTRANSMITTERSPATHWAY | Biosynthesis of neurotransmitters | DBH, GAD1, HDC, PNMT, TH, TPH1 | 6 | DBH(1), GAD1(2), HDC(5), TPH1(2) | 572489 | 10 | 7 | 10 | 2 | 3 | 5 | 1 | 0 | 1 | 0 | 0.01 | 0.69
10 | HSA00150_ANDROGEN_AND_ESTROGEN_METABOLISM | Genes involved in androgen and estrogen metabolism | AKR1C4, AKR1D1, ARSD, ARSE, CARM1, CYP11B1, CYP11B2, CYP19A1, HEMK1, HSD11B1, HSD11B2, HSD17B1, HSD17B12, HSD17B2, HSD17B3, HSD17B7, HSD17B8, HSD3B1, HSD3B2, LCMT1, LCMT2, METTL2B, METTL6, PRMT2, PRMT3, PRMT5, PRMT6, PRMT7, PRMT8, SRD5A1, SRD5A2, STS, SULT1E1, SULT2A1, SULT2B1, UGT1A1, UGT1A10, UGT1A3, UGT1A4, UGT1A5, UGT1A6, UGT1A7, UGT1A8, UGT1A9, UGT2A1, UGT2A3, UGT2B10, UGT2B11, UGT2B15, UGT2B17, UGT2B28, UGT2B4, UGT2B7, WBSCR22 | 53 | AKR1C4(1), AKR1D1(1), CYP11B1(4), CYP19A1(3), HSD17B2(1), HSD17B3(1), HSD3B1(1), HSD3B2(1), LCMT1(2), METTL2B(1), METTL6(3), PRMT3(1), PRMT7(1), PRMT8(2), SRD5A2(1), STS(1), SULT1E1(1), SULT2A1(1), UGT1A4(1), UGT1A6(1), UGT1A8(1), UGT1A9(1), UGT2A3(2), UGT2B11(2), UGT2B17(3), UGT2B28(1), UGT2B4(1), UGT2B7(2) | 4462401 | 42 | 18 | 42 | 9 | 9 | 19 | 6 | 1 | 7 | 0 | 0.012 | 0.7

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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