Kidney Renal Clear Cell Carcinoma: Mutation Analysis (MutSig v2.0)
(primary solid tumor cohort)
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: KIRC-TP

  • Number of patients in set: 293

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:KIRC-TP.final_analysis_set.maf

  • Significantly mutated genes (q ≤ 0.1): 25

  • Mutations seen in COSMIC: 212

  • Significantly mutated genes in COSMIC territory: 5

  • Genes with clustered mutations (≤ 3 aa apart): 174

  • Significantly mutated genesets: 6

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

Mutation Preprocessing

  • Read 293 MAFs of type "Broad"

  • Total number of mutations in input MAFs: 95839

  • After removing 232 mutations outside chr1-24: 95607

  • After removing 6379 blacklisted mutations: 89228

  • After removing 64591 noncoding mutations: 24637

  • After collapsing adjacent/redundant mutations: 24179

Mutation Filtering

  • Number of mutations before filtering: 24179

  • After removing 654 mutations outside gene set: 23525

  • After removing 14 mutations outside category set: 23511

  • After removing 1 "impossible" mutations in

  • gene-patient-category bins of zero coverage: 22842

Results
Breakdown of Mutations by Type

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

type count
Frame_Shift_Del 471
Frame_Shift_Ins 107
In_Frame_Del 48
In_Frame_Ins 8
Missense_Mutation 15492
Nonsense_Mutation 1046
Nonstop_Mutation 21
Silent 5790
Splice_Site 491
Translation_Start_Site 37
Total 23511
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 1719 484078369 3.6e-06 3.6 1.8 2.1
*ApG->G 1167 1342141277 8.7e-07 0.87 0.43 2.1
*Np(A/C/T)->transit 5081 6921093572 7.3e-07 0.73 0.36 2
transver 7528 8747313218 8.6e-07 0.86 0.42 5
indel+null 2220 8747313218 2.5e-07 0.25 0.13 NaN
double_null 6 8747313218 6.9e-10 0.00069 0.00034 NaN
Total 17721 8747313218 2e-06 2 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: KIRC-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: *ApG->G

  • n3 = number of nonsilent mutations of type: *Np(A/C/T)->transit

  • n4 = number of nonsilent mutations of type: transver

  • 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: 25. 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 VHL von Hippel-Lindau tumor suppressor 123072 138 138 92 1 1 13 9 31 84 0 <1.00e-15 1.3e-10 NaN NaN <1.00e-15 <9.06e-12
2 PBRM1 polybromo 1 1470408 108 106 105 1 0 1 6 15 86 0 <1.00e-15 1.8e-06 NaN NaN <1.00e-15 <9.06e-12
3 BAP1 BRCA1 associated protein-1 (ubiquitin carboxy-terminal hydrolase) 589189 27 27 24 1 0 2 6 4 14 1 3.00e-15 0.0042 NaN NaN 3.00e-15 1.81e-11
4 SETD2 SET domain containing 2 1866089 33 33 33 1 2 2 2 6 20 1 7.22e-15 0.0052 NaN NaN 7.22e-15 3.27e-11
5 KDM5C lysine (K)-specific demethylase 5C 1253863 18 18 18 0 0 0 1 5 12 0 5.44e-12 0.044 NaN NaN 5.44e-12 1.97e-08
6 MUC4 mucin 4, cell surface associated 958196 65 41 50 15 4 0 22 35 4 0 5.12e-09 0.16 NaN NaN 5.12e-09 1.55e-05
7 PTEN phosphatase and tensin homolog (mutated in multiple advanced cancers 1) 365609 10 9 10 0 0 0 2 2 6 0 1.23e-08 0.059 NaN NaN 1.23e-08 3.10e-05
8 MTOR mechanistic target of rapamycin (serine/threonine kinase) 2294678 26 24 22 2 1 2 4 19 0 0 1.37e-08 0.043 NaN NaN 1.37e-08 3.10e-05
9 EBPL emopamil binding protein-like 139558 7 6 3 0 1 0 0 6 0 0 1.89e-07 0.2 NaN NaN 1.89e-07 0.000381
10 NBPF10 neuroblastoma breakpoint family, member 10 1006919 25 19 17 5 2 2 5 16 0 0 1.55e-05 0.36 NaN NaN 1.55e-05 0.0281
11 BAGE2 B melanoma antigen family, member 2 101378 4 4 4 0 1 0 1 1 1 0 2.17e-05 0.29 NaN NaN 2.17e-05 0.0357
12 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 963086 10 10 9 0 0 0 5 4 1 0 2.57e-05 0.068 NaN NaN 2.57e-05 0.0375
13 WDR52 WD repeat domain 52 887493 10 9 6 1 1 1 0 8 0 0 2.69e-05 0.35 NaN NaN 2.69e-05 0.0375
14 TPTE2 transmembrane phosphoinositide 3-phosphatase and tensin homolog 2 483148 8 7 8 1 1 0 0 6 1 0 3.70e-05 0.5 NaN NaN 3.70e-05 0.0478
15 TP53 tumor protein p53 372038 7 6 7 1 2 0 3 1 1 0 4.99e-05 0.3 NaN NaN 4.99e-05 0.0572
16 TSPAN19 tetraspanin 19 144817 4 4 4 0 0 0 1 1 2 0 5.06e-05 0.6 NaN NaN 5.06e-05 0.0572
17 GFRAL GDNF family receptor alpha like 357745 5 5 5 0 0 0 2 1 2 0 9.62e-05 0.24 NaN NaN 9.62e-05 0.0894
18 STAG2 stromal antigen 2 1153594 9 9 9 1 2 0 1 3 3 0 9.98e-05 0.55 NaN NaN 9.98e-05 0.0894
19 C5orf13 chromosome 5 open reading frame 13 64167 3 3 3 0 0 1 0 0 2 0 0.000100 0.68 NaN NaN 0.000100 0.0894
20 SFRS15 splicing factor, arginine/serine-rich 15 1032486 9 9 9 0 0 0 4 2 3 0 0.000112 0.076 NaN NaN 0.000112 0.0894
21 GRIN2B glutamate receptor, ionotropic, N-methyl D-aspartate 2B 1319371 11 11 11 0 1 0 4 6 0 0 0.000115 0.042 NaN NaN 0.000115 0.0894
22 ANKRD7 ankyrin repeat domain 7 231177 4 4 4 0 1 1 1 0 1 0 0.000116 0.21 NaN NaN 0.000116 0.0894
23 CR1 complement component (3b/4b) receptor 1 (Knops blood group) 1444581 10 10 7 0 1 0 0 4 5 0 0.000116 0.14 NaN NaN 0.000116 0.0894
24 OR10G7 olfactory receptor, family 10, subfamily G, member 7 275420 5 5 5 1 2 0 0 3 0 0 0.000120 0.48 NaN NaN 0.000120 0.0894
25 CNTNAP4 contactin associated protein-like 4 1140427 9 9 8 0 2 2 2 3 0 0 0.000123 0.048 NaN NaN 0.000123 0.0894
26 NPNT nephronectin 489577 6 6 6 0 2 0 0 3 1 0 0.000166 0.3 NaN NaN 0.000166 0.112
27 CCNB2 cyclin B2 353170 5 5 5 0 0 0 2 1 2 0 0.000166 0.22 NaN NaN 0.000166 0.112
28 LIPI lipase, member I 435398 5 5 5 0 1 0 3 1 0 0 0.000254 0.18 NaN NaN 0.000254 0.161
29 PCLO piccolo (presynaptic cytomatrix protein) 4446380 20 20 19 2 0 6 5 7 2 0 0.000258 0.021 NaN NaN 0.000258 0.161
30 ZNF800 zinc finger protein 800 590395 6 6 6 0 0 1 1 2 2 0 0.000308 0.25 NaN NaN 0.000308 0.186
31 SPAM1 sperm adhesion molecule 1 (PH-20 hyaluronidase, zona pellucida binding) 451804 5 5 5 0 2 0 1 2 0 0 0.000321 0.26 NaN NaN 0.000321 0.188
32 CSMD3 CUB and Sushi multiple domains 3 3360659 21 20 21 3 3 1 6 8 3 0 0.000446 0.16 NaN NaN 0.000446 0.253
33 MLL3 myeloid/lymphoid or mixed-lineage leukemia 3 4339736 20 20 18 2 1 3 0 7 9 0 0.000497 0.07 NaN NaN 0.000497 0.273
34 LPAR4 lysophosphatidic acid receptor 4 327281 4 4 4 0 1 0 0 2 1 0 0.000646 0.54 NaN NaN 0.000646 0.335
35 KCNH7 potassium voltage-gated channel, subfamily H (eag-related), member 7 1090253 8 8 8 1 2 0 0 6 0 0 0.000675 0.41 NaN NaN 0.000675 0.335
VHL

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

PBRM1

Figure S2.  This figure depicts the distribution of mutations and mutation types across the PBRM1 significant gene.

BAP1

Figure S3.  This figure depicts the distribution of mutations and mutation types across the BAP1 significant gene.

SETD2

Figure S4.  This figure depicts the distribution of mutations and mutation types across the SETD2 significant gene.

KDM5C

Figure S5.  This figure depicts the distribution of mutations and mutation types across the KDM5C significant gene.

MUC4

Figure S6.  This figure depicts the distribution of mutations and mutation types across the MUC4 significant gene.

PTEN

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

MTOR

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

EBPL

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

PIK3CA

Figure S10.  This figure depicts the distribution of mutations and mutation types across the PIK3CA significant gene.

WDR52

Figure S11.  This figure depicts the distribution of mutations and mutation types across the WDR52 significant gene.

TPTE2

Figure S12.  This figure depicts the distribution of mutations and mutation types across the TPTE2 significant gene.

TP53

Figure S13.  This figure depicts the distribution of mutations and mutation types across the TP53 significant gene.

TSPAN19

Figure S14.  This figure depicts the distribution of mutations and mutation types across the TSPAN19 significant gene.

GFRAL

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

STAG2

Figure S16.  This figure depicts the distribution of mutations and mutation types across the STAG2 significant gene.

C5orf13

Figure S17.  This figure depicts the distribution of mutations and mutation types across the C5orf13 significant gene.

SFRS15

Figure S18.  This figure depicts the distribution of mutations and mutation types across the SFRS15 significant gene.

GRIN2B

Figure S19.  This figure depicts the distribution of mutations and mutation types across the GRIN2B significant gene.

ANKRD7

Figure S20.  This figure depicts the distribution of mutations and mutation types across the ANKRD7 significant gene.

CR1

Figure S21.  This figure depicts the distribution of mutations and mutation types across the CR1 significant gene.

OR10G7

Figure S22.  This figure depicts the distribution of mutations and mutation types across the OR10G7 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: 5. Number of genes displayed: 10

rank gene description n cos n_cos N_cos cos_ev p q
1 VHL von Hippel-Lindau tumor suppressor 138 541 138 158513 3461 0 0
2 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 10 220 9 64460 3007 0 0
3 PTEN phosphatase and tensin homolog (mutated in multiple advanced cancers 1) 10 767 10 224731 76 6.9e-11 1e-07
4 TP53 tumor protein p53 7 356 7 104308 1411 3.1e-09 3.5e-06
5 KRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog 3 52 3 15236 14812 4.8e-06 0.0043
6 SMARCA4 SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4 7 30 2 8790 2 0.00016 0.12
7 NF2 neurofibromin 2 (merlin) 4 550 4 161150 32 0.00037 0.24
8 ONECUT2 one cut homeobox 2 1 1 1 293 1 0.00059 0.24
9 PDLIM4 PDZ and LIM domain 4 2 1 1 293 1 0.00059 0.24
10 PRDX5 peroxiredoxin 5 1 1 1 293 1 0.00059 0.24

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
8583 VHL von Hippel-Lindau tumor suppressor 133 0 105 319 772 105 319 772
4916 MUC4 mucin 4, cell surface associated 61 0 22 37 78 22 37 78
2407 EBPL emopamil binding protein-like 6 0 10 10 15 10 10 15
8657 WDR52 WD repeat domain 52 10 0 10 10 10 10 10 10
5049 NBPF10 neuroblastoma breakpoint family, member 10 25 0 7 11 11 7 11 11
733 BAP1 BRCA1 associated protein-1 (ubiquitin carboxy-terminal hydrolase) 27 0 6 11 21 6 11 21
1884 CR1 complement component (3b/4b) receptor 1 (Knops blood group) 10 0 6 6 6 6 6 6
4901 MTOR mechanistic target of rapamycin (serine/threonine kinase) 26 0 5 9 19 5 9 19
5050 NBPF9 neuroblastoma breakpoint family, member 9 13 0 3 7 9 3 7 9
8734 XPOT exportin, tRNA (nuclear export receptor for tRNAs) 7 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: 6. 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 VEGFPATHWAY Vascular endothelial growth factor (VEGF) is upregulated by hypoxic conditions and promotes normal blood vessel formation and angiogenesis related to tumor growth or cardiac disease. ARNT, EIF1, EIF1A, EIF2B1, EIF2B2, EIF2B3, EIF2B4, EIF2B5, EIF2S1, EIF2S2, EIF2S3, ELAVL1, FLT1, FLT4, HIF1A, HRAS, KDR, NOS3, PIK3CA, PIK3R1, PLCG1, PRKCA, PRKCB1, PTK2, PXN, SHC1, VEGF, VHL 25 EIF1(1), EIF2B1(2), EIF2B2(1), EIF2B5(2), EIF2S1(1), EIF2S2(1), ELAVL1(1), FLT1(3), FLT4(4), HIF1A(3), KDR(5), NOS3(1), PIK3CA(10), PIK3R1(1), PTK2(1), PXN(2), SHC1(2), VHL(138) 14983008 179 157 132 10 6 15 19 50 89 0 1.7e-07 1.1e-15 3.4e-13
2 HIFPATHWAY Under normal conditions, hypoxia inducible factor HIF-1 is degraded; under hypoxic conditions, it activates transcription of genes controlled by hpoxic response elements (HREs). ARNT, ASPH, COPS5, CREB1, EDN1, EP300, EPO, HIF1A, HSPCA, JUN, LDHA, NOS3, P4HB, VEGF, VHL 13 EP300(6), HIF1A(3), JUN(1), NOS3(1), VHL(138) 7504580 149 143 103 7 1 14 11 37 86 0 1e-06 1.1e-15 3.4e-13
3 HSA04120_UBIQUITIN_MEDIATED_PROTEOLYSIS Genes involved in ubiquitin mediated proteolysis ANAPC1, ANAPC10, ANAPC11, ANAPC2, ANAPC4, ANAPC5, ANAPC7, BTRC, CDC16, CDC20, CDC23, CDC26, CDC27, CUL1, CUL2, CUL3, FBXW11, FBXW7, FZR1, ITCH, LOC728919, RBX1, SKP1, SKP2, SMURF1, SMURF2, TCEB1, TCEB2, UBA1, UBE2C, UBE2D1, UBE2D2, UBE2D3, UBE2D4, UBE2E1, UBE2E2, UBE2E3, VHL, WWP1, WWP2 39 ANAPC1(4), ANAPC2(1), ANAPC4(2), ANAPC5(2), ANAPC7(1), CDC16(2), CDC20(1), CDC23(2), CDC27(5), CUL1(3), CUL2(1), CUL3(2), FBXW11(1), FBXW7(2), FZR1(1), SKP2(1), SMURF1(1), SMURF2(2), TCEB1(2), UBA1(1), UBE2D1(2), UBE2D2(1), UBE2D3(1), UBE2E2(1), VHL(138), WWP2(1) 17820449 181 157 135 13 2 18 23 45 93 0 1.3e-06 7.7e-15 1.6e-12
4 SA_PTEN_PATHWAY PTEN is a tumor suppressor that dephosphorylates the lipid messenger phosphatidylinositol triphosphate. AKT1, AKT2, AKT3, BPNT1, GRB2, ILK, MAPK1, MAPK3, PDK1, PIK3CA, PIK3CD, PIP3-E, PTEN, PTK2B, RBL2, SHC1, SOS1 16 AKT1(1), AKT2(2), AKT3(2), MAPK1(1), MAPK3(1), PDK1(1), PIK3CA(10), PIK3CD(1), PTEN(10), PTK2B(2), RBL2(3), SHC1(2), SOS1(4) 8973555 40 38 39 2 3 2 15 12 8 0 0.00042 7.9e-06 0.0012
5 CDC42RACPATHWAY PI3 kinase stimulates cell migration by activating cdc42, which activates ARP2/3, which in turn promotes formation of new actin fibers. ACTR2, ACTR3, ARHA, ARPC1A, ARPC1B, ARPC2, ARPC3, ARPC4, CDC42, PAK1, PDGFRA, PIK3CA, PIK3R1, RAC1, WASL 14 ACTR2(2), ACTR3(1), ARPC2(1), CDC42(2), PAK1(1), PDGFRA(5), PIK3CA(10), PIK3R1(1), WASL(5) 5877261 28 28 27 2 0 1 11 15 1 0 0.018 0.00036 0.045
6 SA_TRKA_RECEPTOR The TrkA receptor binds nerve growth factor to activate MAP kinase pathways and promote cell growth. AKT1, AKT2, AKT3, ARHA, CDKN1A, ELK1, GRB2, HRAS, MAP2K1, MAP2K2, NGFB, NGFR, NTRK1, PIK3CA, PIK3CD, SHC1, SOS1 15 AKT1(1), AKT2(2), AKT3(2), CDKN1A(1), ELK1(1), MAP2K1(1), NGFR(1), NTRK1(2), PIK3CA(10), PIK3CD(1), SHC1(2), SOS1(4) 7184719 28 28 27 1 2 1 12 12 1 0 0.002 0.00079 0.082
7 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(9), AKT1(1), ATM(13), CDKN1A(1), CSNK1A1(1), FHL2(1), HIC1(1), HIF1A(3), MAPK8(1), TP53(7) 9166900 38 33 38 2 2 0 14 10 12 0 0.0018 0.0016 0.14
8 HSA00950_ALKALOID_BIOSYNTHESIS_I Genes involved in alkaloid biosynthesis I DDC, GOT1, GOT2, TAT, TYR 5 DDC(3), GOT1(2), GOT2(3), TAT(1), TYR(1) 2063429 10 10 10 1 1 0 5 1 3 0 0.2 0.0044 0.34
9 HSA00401_NOVOBIOCIN_BIOSYNTHESIS Genes involved in novobiocin biosynthesis GOT1, GOT2, TAT 3 GOT1(2), GOT2(3), TAT(1) 1153972 6 6 6 1 1 0 3 0 2 0 0.42 0.013 0.92
10 CYSTEINE_METABOLISM CARS, CTH, GOT1, GOT2, LDHA, LDHB, LDHC, MPST 8 CARS(2), CTH(1), GOT1(2), GOT2(3), LDHB(1), LDHC(2), MPST(2) 3003190 13 13 13 2 2 0 4 3 4 0 0.33 0.017 1

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 HSA00950_ALKALOID_BIOSYNTHESIS_I Genes involved in alkaloid biosynthesis I DDC, GOT1, GOT2, TAT, TYR 5 DDC(3), GOT1(2), GOT2(3), TAT(1), TYR(1) 2063429 10 10 10 1 1 0 5 1 3 0 0.2 0.0044 1
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 18 ABCB1(9), AKT1(1), ATM(13), CDKN1A(1), CSNK1A1(1), FHL2(1), HIC1(1), HIF1A(3), MAPK8(1) 8794862 31 27 31 1 0 0 11 9 11 0 0.003 0.01 1
3 HSA00401_NOVOBIOCIN_BIOSYNTHESIS Genes involved in novobiocin biosynthesis GOT1, GOT2, TAT 3 GOT1(2), GOT2(3), TAT(1) 1153972 6 6 6 1 1 0 3 0 2 0 0.42 0.013 1
4 CYSTEINE_METABOLISM CARS, CTH, GOT1, GOT2, LDHA, LDHB, LDHC, MPST 8 CARS(2), CTH(1), GOT1(2), GOT2(3), LDHB(1), LDHC(2), MPST(2) 3003190 13 13 13 2 2 0 4 3 4 0 0.33 0.017 1
5 HSA00272_CYSTEINE_METABOLISM Genes involved in cysteine metabolism CARS, CARS2, CDO1, CTH, GOT1, GOT2, LDHA, LDHAL6A, LDHAL6B, LDHB, LDHC, MPST, SDS, SULT1B1, SULT1C2, SULT1C4, SULT4A1 17 CARS(2), CARS2(3), CTH(1), GOT1(2), GOT2(3), LDHAL6B(1), LDHB(1), LDHC(2), MPST(2), SULT1C2(1), SULT4A1(1) 5521164 19 19 19 2 2 1 5 5 6 0 0.14 0.02 1
6 HSA00130_UBIQUINONE_BIOSYNTHESIS Genes involved in ubiquinone biosynthesis COQ2, COQ3, COQ5, COQ6, COQ7, ND1, ND2, ND3, ND4, ND4L, ND5, ND6, NDUFA12, NDUFA13, NDUFB11 8 COQ5(2), COQ6(1), NDUFA13(3), NDUFB11(1) 1778759 7 7 7 0 2 0 1 3 1 0 0.15 0.037 1
7 CYANOAMINO_ACID_METABOLISM ATP6V0C, SHMT1, GBA3, GGT1, SHMT1, SHMT2 5 GBA3(2), GGT1(1), SHMT1(2), SHMT2(2) 1851827 7 7 7 1 0 0 3 1 3 0 0.38 0.046 1
8 EEA1PATHWAY The FYVE-finger proteins EEA1 and HRS are localized to endosome membranes and regulate sorting and ubiquitination in the vesicle transport system. EEA1, EGF, EGFR, HGS, RAB5A, TF, TFRC 7 EEA1(5), EGF(3), EGFR(2), HGS(3), TF(1), TFRC(2) 5644686 16 16 16 1 2 2 4 5 3 0 0.061 0.05 1
9 CDC42RACPATHWAY PI3 kinase stimulates cell migration by activating cdc42, which activates ARP2/3, which in turn promotes formation of new actin fibers. ACTR2, ACTR3, ARHA, ARPC1A, ARPC1B, ARPC2, ARPC3, ARPC4, CDC42, PAK1, PDGFRA, PIK3CA, PIK3R1, RAC1, WASL 13 ACTR2(2), ACTR3(1), ARPC2(1), CDC42(2), PAK1(1), PDGFRA(5), PIK3R1(1), WASL(5) 4914175 18 18 18 2 0 1 6 11 0 0 0.13 0.051 1
10 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(1), CPS1(5), GLS(1), GLUD1(2), GOT1(2) 3418789 11 11 11 1 0 0 6 2 3 0 0.16 0.052 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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