Glioblastoma Multiforme: 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 v1.5 was used to generate the results found in this report.

Working with individual set: GBM.

Number of patients in set: 276

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

Significantly mutated genes (q ≤ 0.1): 251

Mutations seen in COSMIC: 450

Significantly mutated genes in COSMIC territory: 56

Genes with clustered mutations (&le 3 aa apart): 335

Significantly mutated genesets: 179

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

Results
Breakdown of Mutations by Type

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

type count
De_novo_Start_InFrame 6
De_novo_Start_OutOfFrame 11
Frame_Shift_Del 825
Frame_Shift_Ins 367
In_Frame_Del 328
In_Frame_Ins 36
Indel 1
Missense_Mutation 23424
Nonsense_Mutation 1795
Nonstop_Mutation 17
Silent 8876
Splice_Site_DNP 11
Splice_Site_Del 101
Splice_Site_Ins 28
Splice_Site_ONP 1
Splice_Site_SNP 481
Start_Codon_Del 2
Start_Codon_Ins 1
Stop_Codon_Del 2
Total 36313
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 8794 406970401 0.000022 22 6
*Cp(A/C/T)->T 3993 3448378213 1.2e-06 1.2 0.32
C->(G/A) 5881 3855348614 1.5e-06 1.5 0.42
A->mut 4753 3770634164 1.3e-06 1.3 0.35
indel+null 3854 7625982864 5.1e-07 0.51 0.14
double_null 162 7625982864 2.1e-08 0.021 0.0059
Total 27437 7625982864 3.6e-06 3.6 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. 

Significantly Mutated Genes

Table 3.  Get Full Table A Ranked List of Significantly Mutated Genes. Number of significant genes found: 251. Number of genes displayed: 35

rank gene description N n npat nsite nsil n1 n2 n3 n4 n5 n6 p q
1 TP53 tumor protein p53 344937 91 80 65 1 23 15 12 13 24 4 2.4e-15 4.4e-11
2 EGFR epidermal growth factor receptor (erythroblastic leukemia viral (v-erb-b) oncogene homolog, avian) 1089173 58 54 26 5 9 21 23 5 0 0 8.6e-15 7.6e-11
3 PTEN phosphatase and tensin homolog (mutated in multiple advanced cancers 1) 314597 80 79 65 0 7 19 8 11 35 0 2e-14 1.1e-10
4 IDH1 isocitrate dehydrogenase 1 (NADP+), soluble 349470 15 15 2 0 14 0 1 0 0 0 4.6e-14 1.1e-10
5 NF1 neurofibromin 1 (neurofibromatosis, von Recklinghausen disease, Watson disease) 2380799 34 25 32 1 2 5 3 4 14 6 5.1e-14 1.1e-10
6 RB1 retinoblastoma 1 (including osteosarcoma) 722445 21 21 19 1 1 1 1 0 18 0 5.4e-14 1.1e-10
7 KRTAP5-5 keratin associated protein 5-5 181491 18 16 7 0 0 0 3 1 14 0 5.5e-14 1.1e-10
8 SPTA1 spectrin, alpha, erythrocytic 1 (elliptocytosis 2) 2040988 30 26 28 5 12 4 6 1 7 0 5.5e-14 1.1e-10
9 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 885302 19 19 17 1 3 5 2 7 2 0 5.9e-14 1.1e-10
10 PIK3R1 phosphoinositide-3-kinase, regulatory subunit 1 (alpha) 642722 17 17 14 0 0 3 2 4 8 0 6e-14 1.1e-10
11 MICALCL MICAL C-terminal like 537385 13 13 3 0 0 0 0 1 12 0 2.8e-13 4.5e-10
12 RYR2 ryanodine receptor 2 (cardiac) 3381004 36 28 35 7 21 3 6 6 0 0 1.3e-10 1.9e-07
13 FLG filaggrin 3183335 30 28 30 13 12 6 6 3 3 0 1.4e-09 1.8e-06
14 MUC2 mucin 2, oligomeric mucus/gel-forming 1046521 22 15 19 4 9 1 7 4 1 0 1.5e-09 1.9e-06
15 FOXRED1 FAD-dependent oxidoreductase domain containing 1 345284 9 9 1 0 0 0 0 9 0 0 1.6e-09 1.9e-06
16 MST1 macrophage stimulating 1 (hepatocyte growth factor-like) 467340 10 9 6 0 2 0 0 1 7 0 4e-09 4.5e-06
17 HEATR7B2 934727 13 12 12 5 1 1 5 4 2 0 6.6e-09 6.9e-06
18 KEL Kell blood group, metallo-endopeptidase 619645 12 12 11 3 6 0 3 0 3 0 8.7e-09 8.6e-06
19 GABRA6 gamma-aminobutyric acid (GABA) A receptor, alpha 6 384256 9 9 8 0 2 1 5 1 0 0 3.9e-08 0.000037
20 STAG2 stromal antigen 2 1054509 11 11 11 0 0 1 3 0 7 0 7.2e-08 0.000064
21 COMMD4 COMM domain containing 4 147026 6 6 1 0 0 0 6 0 0 0 9.9e-08 0.000084
22 CRYBA2 crystallin, beta A2 136089 6 6 3 1 0 0 5 1 0 0 1.1e-07 0.000085
23 RIMS2 regulating synaptic membrane exocytosis 2 1148237 16 14 14 1 7 1 3 1 4 0 1.1e-07 0.000085
24 CALN1 calneuron 1 187028 9 9 8 1 8 0 1 0 0 0 1.3e-07 0.000094
25 IL17RA interleukin 17 receptor A 452882 9 9 5 1 1 0 2 6 0 0 1.5e-07 0.00011
26 POTEB 448989 9 9 9 1 2 1 3 3 0 0 2.4e-07 0.00017
27 CNTNAP2 contactin associated protein-like 2 1094783 16 15 16 7 10 1 4 1 0 0 2.5e-07 0.00017
28 HCN1 hyperpolarization activated cyclic nucleotide-gated potassium channel 1 650787 11 10 11 5 3 0 4 2 2 0 3.9e-07 0.00025
29 CDH18 cadherin 18, type 2 661503 12 10 12 3 3 4 2 1 2 0 4.2e-07 0.00026
30 DNASE1L1 deoxyribonuclease I-like 1 189681 6 6 2 1 1 0 5 0 0 0 6.1e-07 0.00036
31 CEACAM16 carcinoembryonic antigen-related cell adhesion molecule 16 186452 7 7 3 0 1 0 6 0 0 0 6.3e-07 0.00037
32 FAM83H family with sequence similarity 83, member H 426683 12 10 10 2 8 0 0 4 0 0 6.8e-07 0.00038
33 C9orf150 chromosome 9 open reading frame 150 144707 6 6 3 0 1 1 0 0 4 0 7.1e-07 0.00038
34 OR5D13 olfactory receptor, family 5, subfamily D, member 13 260757 8 7 8 1 3 1 0 3 1 0 7.2e-07 0.00038
35 SLCO6A1 solute carrier organic anion transporter family, member 6A1 579033 10 10 10 4 4 1 2 3 0 0 7.6e-07 0.00039

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: *Cp(A/C/T)->T .

n3 - number of nonsilent mutations of type: C->(G/A) .

n4 - number of nonsilent mutations of type: A->mut .

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: 56. Number of genes displayed: 10

rank gene description n cos n_cos N_cos cos_ev p q
1 IDH1 isocitrate dehydrogenase 1 (NADP+), soluble 15 3 15 828 22380 0 0
2 PIK3R1 phosphoinositide-3-kinase, regulatory subunit 1 (alpha) 17 33 9 9108 20 0 0
3 EGFR epidermal growth factor receptor (erythroblastic leukemia viral (v-erb-b) oncogene homolog, avian) 58 218 46 60168 640 0 0
4 TP53 tumor protein p53 91 823 91 227148 26340 0 0
5 PTEN phosphatase and tensin homolog (mutated in multiple advanced cancers 1) 80 728 79 200928 2714 0 0
6 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 19 184 15 50784 3911 0 0
7 NF1 neurofibromin 1 (neurofibromatosis, von Recklinghausen disease, Watson disease) 34 285 12 78660 21 0 0
8 RB1 retinoblastoma 1 (including osteosarcoma) 21 267 11 73692 30 0 0
9 PTPN11 protein tyrosine phosphatase, non-receptor type 11 (Noonan syndrome 1) 6 31 4 8556 16 3.6e-08 0.000018
10 BRAF v-raf murine sarcoma viral oncogene homolog B1 6 88 5 24288 42058 3.9e-08 0.000018

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 npairs3 npairs12
2963 EGFR epidermal growth factor receptor (erythroblastic leukemia viral (v-erb-b) oncogene homolog, avian) 58 0 172 195
10104 TP53 tumor protein p53 91 0 133 411
4499 IDH1 isocitrate dehydrogenase 1 (NADP+), soluble 15 0 105 105
7900 PTEN phosphatase and tensin homolog (mutated in multiple advanced cancers 1) 80 0 61 155
3606 FOXRED1 FAD-dependent oxidoreductase domain containing 1 9 0 36 36
5436 LPHN1 latrophilin 1 10 0 16 18
878 BBS1 Bardet-Biedl syndrome 1 8 0 15 15
2202 COL5A3 collagen, type V, alpha 3 11 0 15 15
2215 COMMD4 COMM domain containing 4 6 0 15 15
2317 CRYBA2 crystallin, beta A2 6 0 15 15

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: 179. 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 SIG_INSULIN_RECEPTOR_PATHWAY_IN_CARDIAC_MYOCYTES Genes related to the insulin receptor pathway AKT1, AKT2, AKT3, BRD4, CAP1, CBL, CDC42, CDKN2A, F2RL2, FLOT1, FLOT2, FOXO1A, GRB2, GSK3A, GSK3B, IGFBP1, INPPL1, IRS1, IRS2, IRS4, LNPEP, MAPK1, MAPK3, PARD3, PARD6A, PDK1, PIK3CA, PIK3CD, PIK3R1, PPYR1, PSCD3, PTEN, PTPN1, RAF1, RPS6KA1, RPS6KA2, RPS6KA3, RPS6KB1, SERPINB6, SFN, SHC1, SLC2A4, SORBS1, SOS1, SOS2, YWHAB, YWHAE, YWHAG, YWHAH, YWHAQ, YWHAZ 48 AKT1(1), AKT2(1), AKT3(1), BRD4(7), CBL(1), CDKN2A(3), FLOT1(2), GSK3B(1), IGFBP1(1), INPPL1(4), IRS1(4), IRS4(3), LNPEP(2), MAPK1(3), MAPK3(2), PARD3(2), PARD6A(1), PIK3CA(19), PIK3CD(2), PIK3R1(17), PPYR1(2), PTEN(80), PTPN1(1), RPS6KA2(2), RPS6KA3(5), RPS6KB1(1), SERPINB6(1), SLC2A4(3), SORBS1(2), SOS1(1), SOS2(4), YWHAB(1), YWHAE(2) 23158627 182 128 162 32 30 35 21 36 60 0 <1.00e-15 <1.28e-13
2 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(1), CDKN2A(3), MDM2(1), PIK3CA(19), PIK3R1(17), POLR1A(3), POLR1B(1), POLR1C(1), RB1(21), TBX2(1), TP53(91) 8040458 159 113 126 13 28 28 20 25 54 4 <1.00e-15 <1.28e-13
3 ST_PHOSPHOINOSITIDE_3_KINASE_PATHWAY The phosphoinositide-3 kinase pathway produces the lipid second messenger PIP3 and regulates cell growth, survival, and movement. A1BG, AKT1, AKT2, AKT3, BAD, BTK, CDKN2A, CSL4, DAF, DAPP1, FOXO1A, GRB2, GSK3A, GSK3B, IARS, IGFBP1, INPP5D, P14, PDK1, PIK3CA, PPP1R13B, PSCD3, PTEN, RPS6KA1, RPS6KA2, RPS6KA3, RPS6KB1, SFN, SHC1, SOS1, SOS2, TEC, YWHAB, YWHAE, YWHAG, YWHAH, YWHAQ, YWHAZ 33 A1BG(2), AKT1(1), AKT2(1), AKT3(1), BTK(1), CDKN2A(3), GSK3B(1), IARS(4), IGFBP1(1), INPP5D(6), PIK3CA(19), PTEN(80), RPS6KA2(2), RPS6KA3(5), RPS6KB1(1), SOS1(1), SOS2(4), TEC(5), YWHAB(1), YWHAE(2) 14274206 141 109 124 17 23 35 15 23 45 0 <1.00e-15 <1.28e-13
4 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 17 ABCB1(4), AKT1(1), ATM(7), CDKN1A(1), CPB2(1), FHL2(1), HIF1A(1), IGFBP3(1), MDM2(1), NFKBIB(1), TP53(91) 8064819 110 83 84 5 29 22 13 16 26 4 2.44e-15 1.28e-13
5 APOPTOSIS_GENMAPP APAF1, BAK1, BCL2L7P1, BAX, BCL2, BCL2L1, BID, BIRC2, BIRC3, BIRC4, CASP2, CASP3, CASP6, CASP7, CASP8, CASP9, CYCS, FADD, FAS, FASLG, GZMB, IKBKG, JUN, MAP2K4, MAP3K1, MAP3K14, MAPK10, MCL1, MDM2, MYC, NFKB1, NFKBIA, PARP1, PRF1, RELA, RIPK1, TNF, TNFRSF1A, TNFRSF1B, TNFSF10, TP53, TRADD, TRAF1, TRAF2 41 APAF1(1), BCL2(3), BID(4), BIRC2(1), BIRC3(1), CASP2(1), CASP6(1), GZMB(3), MAP3K1(5), MAP3K14(2), MDM2(1), NFKB1(1), NFKBIA(2), PARP1(3), PRF1(3), RIPK1(1), TNFRSF1A(2), TNFRSF1B(2), TNFSF10(5), TP53(91), TRAF1(1), TRAF2(2) 15017861 136 96 107 18 31 20 25 25 31 4 2.78e-15 1.28e-13
6 ERBB3PATHWAY Neuregulins bind to the receptor tyrosine kinases ErbB3 and ErbB4, surface-localized receptors whose overexpression induces tumor formation. EGF, EGFR, ERBB3, NRG1, UBE2D1 5 EGF(3), EGFR(58), ERBB3(4), NRG1(4) 4194729 69 59 37 7 13 21 26 8 1 0 4.11e-15 1.28e-13
7 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(8), DAXX(4), PAX3(3), PML(2), RARA(5), RB1(21), SIRT1(2), SP100(3), TNFRSF1A(2), TNFRSF1B(2), TP53(91) 7623942 143 102 112 11 31 21 20 21 46 4 4.55e-15 1.28e-13
8 G2PATHWAY Activated Cdc2-cyclin B kinase regulates the G2/M transition; DNA damage stimulates the DNA-PK/ATM/ATR kinases, which inactivate Cdc2. ATM, ATR, BRCA1, CCNB1, CDC2, CDC25A, CDC25B, CDC25C, CDC34, CDKN1A, CDKN2D, CHEK1, CHEK2, EP300, GADD45A, MDM2, MYT1, PLK, PRKDC, RPS6KA1, TP53, WEE1, YWHAH, YWHAQ 22 ATM(7), ATR(9), BRCA1(4), CDC25B(1), CDKN1A(1), CDKN2D(1), CHEK1(5), EP300(6), MDM2(1), MYT1(7), PRKDC(5), TP53(91) 16932144 138 96 112 10 34 23 22 21 32 6 4.88e-15 1.28e-13
9 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(1), AKT3(1), BPNT1(1), ILK(2), MAPK1(3), MAPK3(2), PIK3CA(19), PIK3CD(2), PTEN(80), PTK2B(1), RBL2(1), SOS1(1) 8079012 115 104 98 7 14 26 13 24 38 0 5.55e-15 1.28e-13
10 HSA04010_MAPK_SIGNALING_PATHWAY Genes involved in MAPK signaling pathway ACVR1B, ACVR1C, AKT1, AKT2, AKT3, ARRB1, ARRB2, ATF2, ATF4, BDNF, BRAF, CACNA1A, CACNA1B, CACNA1C, CACNA1D, CACNA1E, CACNA1F, CACNA1G, CACNA1H, CACNA1I, CACNA1S, CACNA2D1, CACNA2D2, CACNA2D3, CACNA2D4, CACNB1, CACNB2, CACNB3, CACNB4, CACNG1, CACNG2, CACNG3, CACNG4, CACNG5, CACNG6, CACNG7, CACNG8, CASP3, CD14, CDC25B, CDC42, CHP, CHUK, CRK, CRKL, DAXX, DDIT3, DUSP1, DUSP10, DUSP14, DUSP16, DUSP2, DUSP3, DUSP4, DUSP5, DUSP6, DUSP7, DUSP8, DUSP9, ECSIT, EGF, EGFR, ELK1, ELK4, EVI1, FAS, FASLG, FGF1, FGF10, FGF11, FGF12, FGF13, FGF14, FGF16, FGF17, FGF18, FGF19, FGF2, FGF20, FGF21, FGF22, FGF23, FGF3, FGF4, FGF5, FGF6, FGF7, FGF8, FGF9, FGFR1, FGFR2, FGFR3, FGFR4, FLNA, FLNB, FLNC, FOS, GADD45A, GADD45B, GADD45G, GNA12, GNG12, GRB2, HRAS, IKBKB, IKBKG, IL1A, IL1B, IL1R1, IL1R2, JUN, JUND, KRAS, LOC653852, MAP2K1, MAP2K1IP1, MAP2K2, MAP2K3, MAP2K4, MAP2K5, MAP2K6, MAP2K7, MAP3K1, MAP3K10, MAP3K12, MAP3K13, MAP3K14, MAP3K2, MAP3K3, MAP3K4, MAP3K5, MAP3K6, MAP3K7, MAP3K7IP1, MAP3K7IP2, MAP3K8, MAP4K1, MAP4K2, MAP4K3, MAP4K4, MAPK1, MAPK10, MAPK11, MAPK12, MAPK13, MAPK14, MAPK3, MAPK7, MAPK8, MAPK8IP1, MAPK8IP2, MAPK8IP3, MAPK9, MAPKAPK2, MAPKAPK3, MAPKAPK5, MAPT, MAX, MEF2C, MKNK1, MKNK2, MOS, MRAS, MYC, NF1, NFATC2, NFATC4, NFKB1, NFKB2, NGFB, NLK, NR4A1, NRAS, NTF3, NTF5, NTRK1, NTRK2, PAK1, PAK2, PDGFA, PDGFB, PDGFRA, PDGFRB, PLA2G10, PLA2G12A, PLA2G12B, PLA2G1B, PLA2G2A, PLA2G2D, PLA2G2E, PLA2G2F, PLA2G3, PLA2G4A, PLA2G5, PLA2G6, PPM1A, PPM1B, PPP3CA, PPP3CB, PPP3CC, PPP3R1, PPP3R2, PPP5C, PRKACA, PRKACB, PRKACG, PRKCA, PRKCB1, PRKCG, PRKX, PRKY, PTPN5, PTPN7, PTPRR, RAC1, RAC2, RAC3, RAF1, RAP1A, RAP1B, RAPGEF2, RASA1, RASA2, RASGRF1, RASGRF2, RASGRP1, RASGRP2, RASGRP3, RASGRP4, RPS6KA1, RPS6KA2, RPS6KA3, RPS6KA4, RPS6KA5, RPS6KA6, RRAS, RRAS2, SOS1, SOS2, SRF, STK3, STK4, STMN1, TAOK1, TAOK2, TAOK3, TGFB1, TGFB2, TGFB3, TGFBR1, TGFBR2, TNF, TNFRSF1A, TP53, TRAF2, TRAF6, ZAK 246 ACVR1C(2), AKT1(1), AKT2(1), AKT3(1), ATF2(1), ATF4(1), BDNF(1), BRAF(6), CACNA1A(4), CACNA1B(7), CACNA1C(5), CACNA1D(9), CACNA1E(9), CACNA1F(10), CACNA1G(6), CACNA1H(9), CACNA1I(5), CACNA1S(12), CACNA2D1(8), CACNA2D2(1), CACNA2D3(3), CACNA2D4(1), CACNB2(1), CACNB3(1), CACNG1(1), CACNG2(1), CACNG3(4), CACNG6(1), CACNG7(1), CACNG8(1), CD14(2), CDC25B(1), CHUK(4), DAXX(4), DDIT3(1), DUSP10(1), DUSP14(1), DUSP16(1), DUSP2(2), DUSP4(3), DUSP8(1), DUSP9(1), EGF(3), EGFR(58), ELK1(1), ELK4(1), FGF10(1), FGF13(1), FGF14(2), FGF18(1), FGF2(1), FGF20(2), FGF21(1), FGF23(3), FGF3(1), FGF6(3), FGF9(1), FGFR1(3), FGFR2(3), FGFR3(2), FGFR4(3), FLNA(14), FLNB(4), FLNC(6), FOS(1), GADD45B(1), GNA12(2), IKBKB(2), IL1R1(2), KRAS(1), MAP2K1(1), MAP2K2(1), MAP2K3(1), MAP2K5(1), MAP2K7(1), MAP3K1(5), MAP3K10(3), MAP3K12(5), MAP3K13(2), MAP3K14(2), MAP3K2(1), MAP3K3(4), MAP3K4(2), MAP3K5(1), MAP3K6(5), MAP3K7(2), MAP4K1(1), MAP4K2(1), MAP4K3(1), MAP4K4(5), MAPK1(3), MAPK13(1), MAPK14(1), MAPK3(2), MAPK7(3), MAPK8IP1(3), MAPK8IP2(3), MAPK8IP3(5), MAPK9(2), MAPKAPK2(1), MAPKAPK3(1), MAPT(1), MAX(2), MEF2C(1), MKNK1(1), NF1(34), NFATC2(1), NFATC4(2), NFKB1(1), NFKB2(1), NR4A1(3), NRAS(1), NTF3(1), NTRK1(4), NTRK2(1), PAK1(2), PDGFRA(10), PDGFRB(5), PLA2G12A(3), PLA2G2A(5), PLA2G2F(2), PLA2G3(2), PLA2G4A(5), PLA2G5(1), PLA2G6(3), PPM1B(1), PPP3CB(1), PPP3R1(1), PPP3R2(1), PPP5C(1), PRKACG(1), PRKCA(3), PRKCG(1), PRKX(2), PTPRR(2), RAP1B(2), RAPGEF2(4), RASA2(1), RASGRF1(5), RASGRF2(6), RASGRP1(1), RASGRP2(2), RASGRP3(2), RASGRP4(3), RPS6KA2(2), RPS6KA3(5), RRAS2(3), SOS1(1), SOS2(4), SRF(2), STK3(2), STK4(1), STMN1(1), TAOK1(1), TAOK2(2), TAOK3(2), TGFB1(1), TGFB2(1), TGFBR1(1), TGFBR2(5), TNFRSF1A(2), TP53(91), TRAF2(2), ZAK(1) 111569559 592 212 520 148 184 87 111 98 100 12 5.66e-15 1.28e-13

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

rank geneset description genes N_genes mut_tally N n npat nsite nsil n1 n2 n3 n4 n5 n6 p q
1 HSA04640_HEMATOPOIETIC_CELL_LINEAGE Genes involved in hematopoietic cell lineage ANPEP, CD14, CD19, CD1A, CD1B, CD1C, CD1D, CD1E, CD2, CD22, CD24, CD33, CD34, CD36, CD37, CD38, CD3D, CD3E, CD3G, CD4, CD44, CD5, CD55, CD59, CD7, CD8A, CD8B, CD9, CR1, CR2, CSF1, CSF1R, CSF2, CSF2RA, CSF3, CSF3R, DNTT, EPO, EPOR, FCER2, FCGR1A, FLT3, FLT3LG, GP1BA, GP1BB, GP5, GP9, GYPA, HLA-DRA, HLA-DRB1, HLA-DRB3, HLA-DRB4, HLA-DRB5, IL11, IL11RA, IL1A, IL1B, IL1R1, IL1R2, IL2RA, IL3, IL3RA, IL4, IL4R, IL5, IL5RA, IL6, IL6R, IL7, IL7R, IL9R, ITGA1, ITGA2, ITGA2B, ITGA3, ITGA4, ITGA5, ITGA6, ITGAM, ITGB3, KIT, KITLG, MME, MS4A1, TFRC, THPO, TNF, TPO 80 ANPEP(3), CD14(2), CD19(2), CD1B(1), CD1D(2), CD1E(1), CD22(5), CD33(3), CD34(2), CD36(2), CD38(2), CD3E(1), CD3G(1), CD4(3), CD44(4), CD5(2), CD55(2), CD7(2), CD8A(1), CD8B(1), CD9(2), CR1(5), CR2(6), CSF1R(3), CSF3R(2), DNTT(2), EPO(1), EPOR(1), FLT3(7), FLT3LG(1), GP9(1), GYPA(1), HLA-DRA(1), HLA-DRB1(2), HLA-DRB5(2), IL1R1(2), IL2RA(3), IL4(1), IL4R(6), IL5RA(1), IL6(2), IL6R(2), IL7(1), IL7R(1), ITGA1(1), ITGA2(4), ITGA2B(2), ITGA3(2), ITGA4(7), ITGA5(1), ITGA6(2), ITGAM(8), ITGB3(1), KIT(3), KITLG(2), MS4A1(2), TFRC(2), THPO(1), TPO(4) 31730473 140 79 136 52 54 23 28 23 12 0 0.00054 0.23
2 FXRPATHWAY The nuclear receptor transcription factors FXR and LXR are activated by cholesterol metabolites and regulate cholesterol homeostasis. FABP6, LDLR, NR0B2, NR1H3, NR1H4, RXRA 6 LDLR(4), NR0B2(3), NR1H3(1), NR1H4(3), RXRA(3) 2161711 14 14 14 3 3 2 4 3 2 0 0.00076 0.23
3 BLOOD_CLOTTING_CASCADE F10, F11, F12, F13B, F2, F5, F7, F8, F8A1, F9, FGA, FGB, FGG, LPA, PLG, PLAT, PLAU, PLG, SERPINB2, SERPINE1, SERPINF2, VWF 20 F10(1), F13B(2), F2(1), F5(9), F7(1), F8(8), F9(4), FGA(3), FGB(1), FGG(4), LPA(6), PLAU(2), PLG(2), SERPINB2(2), SERPINE1(1), SERPINF2(1), VWF(10) 14027949 58 43 58 22 21 10 11 5 11 0 0.0011 0.23
4 TYROSINE_METABOLISM ABP1, ADH1A, ADH1A, ADH1B, ADH1C, ADH1B, ADH1C, ADH4, ADH6, ADH7, ADHFE1, ALDH1A3, ALDH3A1, ALDH3B1, ALDH3B2, AOC2, AOC3, AOX1, COMT, DBH, DCT, DDC, FAH, GOT1, GOT2, GSTZ1, HGD, HPD, MAOA, MAOB, PNMT, TAT, TH, TPO, TYR 31 ABP1(9), ADH1A(4), ADH1B(3), ADH1C(3), ADH6(2), ADH7(1), ALDH1A3(1), ALDH3A1(3), ALDH3B1(2), ALDH3B2(1), AOC2(2), AOC3(2), AOX1(7), COMT(2), DBH(6), DDC(1), FAH(1), GOT1(1), HPD(1), MAOB(1), PNMT(1), TAT(3), TPO(4), TYR(5) 12332970 66 42 64 14 35 9 9 13 0 0 0.0019 0.29
5 HSA01430_CELL_COMMUNICATION Genes involved in cell communication ACTB, ACTG1, CHAD, COL11A1, COL11A2, COL17A1, COL1A1, COL1A2, COL2A1, COL3A1, COL4A1, COL4A2, COL4A4, COL4A6, COL5A1, COL5A2, COL5A3, COL6A1, COL6A2, COL6A3, COL6A6, COMP, DES, DSC1, DSC2, DSC3, DSG1, DSG2, DSG3, DSG4, FN1, GJA1, GJA10, GJA3, GJA4, GJA5, GJA8, GJA9, GJB1, GJB2, GJB3, GJB4, GJB5, GJB6, GJB7, GJC1, GJC2, GJC3, GJD2, GJD3, GJD4, IBSP, INA, ITGA6, ITGB4, KRT1, KRT10, KRT12, KRT13, KRT14, KRT15, KRT16, KRT17, KRT18, KRT19, KRT2, KRT20, KRT23, KRT24, KRT25, KRT27, KRT28, KRT3, KRT31, KRT32, KRT33A, KRT33B, KRT34, KRT35, KRT36, KRT37, KRT38, KRT39, KRT4, KRT40, KRT5, KRT6A, KRT6B, KRT6C, KRT7, KRT71, KRT72, KRT73, KRT74, KRT75, KRT76, KRT77, KRT78, KRT79, KRT8, KRT81, KRT82, KRT83, KRT84, KRT85, KRT86, KRT9, LAMA1, LAMA2, LAMA3, LAMA4, LAMA5, LAMB1, LAMB2, LAMB3, LAMB4, LAMC1, LAMC2, LAMC3, LMNA, LMNB1, LMNB2, LOC728760, NES, PRPH, RELN, SPP1, THBS1, THBS2, THBS3, THBS4, TNC, TNN, TNR, TNXB, VIM, VTN, VWF 130 ACTB(1), CHAD(1), COL11A1(8), COL11A2(9), COL17A1(3), COL1A1(4), COL1A2(9), COL2A1(2), COL3A1(5), COL4A1(4), COL4A2(8), COL4A4(4), COL4A6(5), COL5A1(3), COL5A2(5), COL5A3(11), COL6A1(5), COL6A2(3), COL6A6(7), COMP(1), DES(3), DSC1(5), DSC2(2), DSC3(2), DSG1(4), DSG2(1), DSG4(10), FN1(3), GJA1(1), GJA10(1), GJA8(1), GJA9(1), GJB1(4), GJB3(2), GJB5(2), GJB6(1), GJB7(1), GJC1(1), GJC2(1), GJC3(1), GJD4(3), INA(2), ITGA6(2), ITGB4(5), KRT1(2), KRT10(1), KRT12(3), KRT13(4), KRT14(3), KRT15(1), KRT16(4), KRT17(3), KRT18(3), KRT2(3), KRT20(1), KRT24(1), KRT25(3), KRT28(3), KRT3(1), KRT31(3), KRT32(2), KRT33A(3), KRT33B(2), KRT34(3), KRT36(4), KRT37(2), KRT38(2), KRT4(2), KRT5(1), KRT6A(1), KRT6B(2), KRT6C(1), KRT7(3), KRT72(1), KRT73(1), KRT74(3), KRT75(2), KRT76(2), KRT77(2), KRT78(1), KRT79(2), KRT8(3), KRT81(1), KRT82(1), KRT83(2), KRT84(2), KRT85(2), KRT9(3), LAMA1(17), LAMA2(12), LAMA3(7), LAMA4(4), LAMA5(9), LAMB1(4), LAMB2(3), LAMB3(4), LAMB4(11), LAMC1(2), LAMC2(6), LAMC3(5), LMNB1(1), LMNB2(3), NES(3), RELN(20), SPP1(1), THBS1(3), THBS2(5), THBS3(1), THBS4(2), TNC(7), TNN(5), TNR(2), TNXB(6), VIM(1), VWF(10) 92368007 406 151 395 169 150 79 74 49 52 2 0.0028 0.34
6 HSA04612_ANTIGEN_PROCESSING_AND_PRESENTATION Genes involved in antigen processing and presentation B2M, CALR, CANX, CD4, CD74, CD8A, CD8B, CIITA, CREB1, CTSB, CTSL1, CTSS, HLA-A, HLA-A29.1, HLA-B, HLA-C, HLA-DMA, HLA-DMB, HLA-DOA, HLA-DOB, HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQA2, HLA-DQB1, HLA-DQB2, HLA-DRA, HLA-DRB1, HLA-DRB3, HLA-DRB4, HLA-DRB5, HLA-E, HLA-F, HLA-G, HSP90AA1, HSP90AB1, HSPA5, IFI30, IFNA1, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA2, IFNA21, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, KIR2DL1, KIR2DL2, KIR2DL3, KIR2DL4, KIR2DL5A, KIR2DS1, KIR2DS2, KIR2DS3, KIR2DS4, KIR2DS5, KIR3DL1, KIR3DL2, KIR3DL3, KLRC1, KLRC2, KLRC3, KLRC4, KLRD1, LGMN, LTA, NFYA, NFYB, NFYC, PDIA3, PSME1, PSME2, RFX5, RFXANK, RFXAP, TAP1, TAP2, TAPBP 73 B2M(2), CANX(4), CD4(3), CD8A(1), CD8B(1), CIITA(7), CTSS(2), HLA-A(1), HLA-B(1), HLA-DMA(1), HLA-DMB(1), HLA-DOA(3), HLA-DOB(2), HLA-DPA1(1), HLA-DQA2(1), HLA-DQB1(2), HLA-DRA(1), HLA-DRB1(2), HLA-DRB5(2), HLA-F(2), HSP90AA1(1), HSP90AB1(2), HSPA5(2), IFNA13(1), IFNA14(1), IFNA17(1), IFNA21(1), IFNA5(1), IFNA7(2), KIR2DL1(2), KIR2DL4(1), KIR3DL1(1), KLRC1(1), KLRC3(3), LGMN(1), NFYB(1), NFYC(3), PDIA3(1), PSME1(1), PSME2(1), TAP1(4), TAP2(2) 18456357 74 49 71 27 16 11 17 15 15 0 0.005 0.41
7 IL17PATHWAY Activated T cells secrete IL-17, which stimulates fibroblasts and other cells to secrete inflammatory and hematopoietic cytokines. CD2, CD34, CD3D, CD3E, CD3G, CD3Z, CD4, CD58, CD8A, CSF3, IL17, IL3, IL6, IL8, KITLG, TRA@, TRB@ 13 CD34(2), CD3E(1), CD3G(1), CD4(3), CD58(1), CD8A(1), IL6(2), KITLG(2) 2527581 13 12 11 3 4 0 3 4 2 0 0.0052 0.41
8 CTLPATHWAY Cytotoxic T lymphocytes induce apoptosis in infected cells presenting antigen-MHC-I complexes via the perforin and Fas/Fas ligand pathways. B2M, CD3D, CD3E, CD3G, CD3Z, GZMB, HLA-A, ICAM1, ITGAL, ITGB2, PRF1, TNFRSF6, TNFSF6, TRA@, TRB@ 10 B2M(2), CD3E(1), CD3G(1), GZMB(3), HLA-A(1), ITGAL(4), ITGB2(5), PRF1(3) 3417489 20 15 20 14 6 1 4 1 8 0 0.0054 0.41
9 DCPATHWAY Dendritic cells internalize and present antigen, after which they migrate to lymphocyte-rich tissues and induce T and B cell differentiation. ANPEP, CD2, CD33, CD5, CD7, CSF2, IFNA1, IFNB1, IFNG, IL10, IL12A, IL12B, IL13, IL3, IL4, IL5, ITGAX, TLR2, TLR4, TLR7, TLR9, TNFRSF5 21 ANPEP(3), CD33(3), CD5(2), CD7(2), IFNB1(1), IFNG(1), IL12B(1), IL4(1), ITGAX(7), TLR2(4), TLR4(1), TLR7(5), TLR9(2) 7416008 33 24 33 13 13 6 9 3 2 0 0.006 0.41
10 NEUROTRANSMITTERSPATHWAY Biosynthesis of neurotransmitters DBH, GAD1, HDC, PNMT, TH, TPH1 6 DBH(6), GAD1(4), HDC(3), PNMT(1), TPH1(3) 2333567 17 13 17 6 10 4 2 1 0 0 0.007 0.43
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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  • Maintainer = Dan DiCara