Uterine Corpus Endometrioid Carcinoma: 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: UCEC.

Number of patients in set: 248

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): 157

Mutations seen in COSMIC: 1006

Significantly mutated genes in COSMIC territory: 47

Genes with clustered mutations (&le 3 aa apart): 2333

Significantly mutated genesets: 75

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
Frame_Shift_Del 1071
Frame_Shift_Ins 475
In_Frame_Del 765
In_Frame_Ins 146
Missense_Mutation 115579
Nonsense_Mutation 11940
Nonstop_Mutation 138
Silent 40149
Splice_Site 2655
Total 172918
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 38705 409266464 0.000095 95 5.4 2.1
*Cp(A/C/T)->mut 51453 3453658664 0.000015 15 0.85 3.3
A->mut 24338 3744388816 6.5e-06 6.5 0.37 3.9
*CpG->(G/A) 1083 409266464 2.6e-06 2.6 0.15 2.7
indel+null 16306 7607313944 2.1e-06 2.1 0.12 NaN
double_null 884 7607313944 1.2e-07 0.12 0.0067 NaN
Total 132769 7607313944 0.000017 17 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. 

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: 157. Number of genes displayed: 35

rank gene description N n npat nsite nsil n1 n2 n3 n4 n5 n6 p_ns_s p q
1 PTEN phosphatase and tensin homolog (mutated in multiple advanced cancers 1) 309504 227 161 134 5 19 29 21 33 98 27 4.9e-12 <1.00e-15 <1.83e-12
2 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 815176 172 132 76 3 31 61 68 3 9 0 2.1e-11 <1.00e-15 <1.83e-12
3 ARID1A AT rich interactive domain 1A (SWI-like) 1428976 94 83 79 5 2 7 5 1 65 14 0.00015 <1.00e-15 <1.83e-12
4 PIK3R1 phosphoinositide-3-kinase, regulatory subunit 1 (alpha) 585280 100 83 77 2 4 4 13 1 63 15 0.0021 <1.00e-15 <1.83e-12
5 CTNNB1 catenin (cadherin-associated protein), beta 1, 88kDa 595696 80 74 25 7 5 61 14 0 0 0 0.0034 <1.00e-15 <1.83e-12
6 TP53 tumor protein p53 317688 74 69 50 2 23 18 15 1 17 0 2.8e-06 <1.00e-15 <1.83e-12
7 KRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog 175336 52 52 11 2 1 46 4 1 0 0 0.0067 <1.00e-15 <1.83e-12
8 CTCF CCCTC-binding factor (zinc finger protein) 551552 49 45 39 1 8 4 7 0 28 2 0.00095 <1.00e-15 <1.83e-12
9 FBXW7 F-box and WD repeat domain containing 7 640832 46 39 30 1 22 12 2 1 8 1 0.00048 <1.00e-15 <1.83e-12
10 FGFR2 fibroblast growth factor receptor 2 (bacteria-expressed kinase, keratinocyte growth factor receptor, craniofacial dysostosis 1, Crouzon syndrome, Pfeiffer syndrome, Jackson-Weiss syndrome) 691920 34 31 19 3 3 5 13 9 3 1 0.0097 <1.00e-15 <1.83e-12
11 SPOP speckle-type POZ protein 287928 23 21 18 0 5 8 6 0 4 0 0.0041 1.11e-15 1.85e-12
12 PPP2R1A protein phosphatase 2 (formerly 2A), regulatory subunit A , alpha isoform 453840 30 27 18 3 10 17 1 0 2 0 0.0023 5.44e-15 8.29e-12
13 P2RY11 purinergic receptor P2Y, G-protein coupled, 11 5704 9 9 9 3 3 4 0 1 1 0 0.3 6.34e-12 8.91e-09
14 CHD4 chromodomain helicase DNA binding protein 4 1460720 43 35 38 2 16 16 8 0 2 1 0.0046 2.01e-10 2.63e-07
15 CCND1 cyclin D1 222952 15 15 13 1 1 7 3 0 4 0 0.084 3.17e-10 3.86e-07
16 FAM9A family with sequence similarity 9, member A 255688 20 14 20 1 2 12 1 0 4 1 0.096 1.12e-09 1.28e-06
17 NFE2L2 nuclear factor (erythroid-derived 2)-like 2 449872 15 15 12 0 2 3 5 3 2 0 0.016 5.83e-09 6.27e-06
18 FOXA2 forkhead box A2 227912 12 12 12 1 1 3 2 0 6 0 0.27 7.77e-09 7.90e-06
19 ARID5B AT rich interactive domain 5B (MRF1-like) 894536 34 29 34 9 5 5 8 2 13 1 0.57 9.03e-09 8.69e-06
20 TNFAIP6 tumor necrosis factor, alpha-induced protein 6 212784 12 12 8 0 2 4 0 0 6 0 0.18 1.20e-08 0.000011
21 MORC4 MORC family CW-type zinc finger 4 685472 28 20 26 2 6 10 1 0 11 0 0.083 2.65e-08 0.000023
22 CYLC1 cylicin, basic protein of sperm head cytoskeleton 1 490048 27 18 27 2 0 16 7 0 4 0 0.13 3.37e-08 0.000028
23 RBMX RNA binding motif protein, X-linked 313224 14 13 8 0 1 4 2 0 7 0 0.3 9.23e-08 0.000073
24 RASA1 RAS p21 protein activator (GTPase activating protein) 1 807488 30 22 28 3 5 9 4 0 11 1 0.084 1.52e-07 0.00012
25 SOX17 SRY (sex determining region Y)-box 17 91512 7 7 3 0 0 6 0 0 1 0 0.15 6.26e-07 0.00046
26 SGK1 serum/glucocorticoid regulated kinase 1 480376 16 15 14 3 2 5 1 1 7 0 0.52 1.51e-06 0.0011
27 ZNF471 zinc finger protein 471 470456 21 15 16 1 0 12 3 0 6 0 0.13 1.67e-06 0.0011
28 ANKRD31 ankyrin repeat domain 31 553040 31 17 31 2 1 17 9 0 3 1 0.066 3.81e-06 0.0025
29 SYCP1 synaptonemal complex protein 1 757640 19 16 19 2 1 7 2 0 6 3 0.43 4.23e-06 0.0027
30 TCP11L2 t-complex 11 (mouse)-like 2 395808 18 14 18 0 3 5 3 0 7 0 0.011 4.82e-06 0.0029
31 SIN3A SIN3 homolog A, transcription regulator (yeast) 967696 29 21 27 3 5 7 7 0 10 0 0.13 5.09e-06 0.0030
32 LOC642587 79112 7 7 4 2 1 1 0 0 5 0 0.8 6.10e-06 0.0035
33 CHEK2 CHK2 checkpoint homolog (S. pombe) 351912 14 13 13 0 0 4 5 0 5 0 0.039 8.14e-06 0.0045
34 MAX MYC associated factor X 209064 12 11 8 0 3 3 5 0 1 0 0.048 8.32e-06 0.0045
35 RUNDC3B RUN domain containing 3B 340752 14 11 12 0 1 4 3 0 6 0 0.044 9.98e-06 0.0052

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)->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 .

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: 47. Number of genes displayed: 10

rank gene description n cos n_cos N_cos cos_ev p q
1 PIK3R1 phosphoinositide-3-kinase, regulatory subunit 1 (alpha) 100 33 39 8184 111 0 0
2 KRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog 52 51 48 12648 554391 0 0
3 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 172 184 150 45632 35669 0 0
4 CTNNB1 catenin (cadherin-associated protein), beta 1, 88kDa 80 101 67 25048 23813 0 0
5 FGFR2 fibroblast growth factor receptor 2 (bacteria-expressed kinase, keratinocyte growth factor receptor, craniofacial dysostosis 1, Crouzon syndrome, Pfeiffer syndrome, Jackson-Weiss syndrome) 34 49 24 12152 113 0 0
6 FBXW7 F-box and WD repeat domain containing 7 46 91 29 22568 852 0 0
7 PTEN phosphatase and tensin homolog (mutated in multiple advanced cancers 1) 227 728 218 180544 14938 0 0
8 TP53 tumor protein p53 74 308 72 76384 24186 0 0
9 NRAS neuroblastoma RAS viral (v-ras) oncogene homolog 9 28 6 6944 6490 4e-09 2e-06
10 RB1 retinoblastoma 1 (including osteosarcoma) 26 267 11 66216 30 4.3e-08 0.000019

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
11550 PTEN phosphatase and tensin homolog (mutated in multiple advanced cancers 1) 227 0 1569 2050 2930 1569 2050 2930
7591 KRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog 52 0 661 949 994 661 949 994
10793 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 172 0 573 1075 1553 573 1075 1553
3516 CTNNB1 catenin (cadherin-associated protein), beta 1, 88kDa 80 0 434 1165 2176 434 1165 2176
14928 TP53 tumor protein p53 74 0 89 167 417 89 167 417
5243 FGFR2 fibroblast growth factor receptor 2 (bacteria-expressed kinase, keratinocyte growth factor receptor, craniofacial dysostosis 1, Crouzon syndrome, Pfeiffer syndrome, Jackson-Weiss syndrome) 34 0 56 56 78 56 56 78
5154 FBXW7 F-box and WD repeat domain containing 7 46 0 50 53 68 50 53 68
11062 POLE polymerase (DNA directed), epsilon 47 0 39 42 60 39 42 60
11232 PPP2R1A protein phosphatase 2 (formerly 2A), regulatory subunit A , alpha isoform 30 0 37 48 77 37 48 77
15264 TTN titin 525 0 35 53 104 35 53 104

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: 75. 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(8), CDKN2A(2), E2F1(9), MDM2(4), MYC(8), PIK3CA(172), PIK3R1(100), POLR1A(16), POLR1B(16), POLR1C(2), POLR1D(3), RAC1(1), RB1(26), TBX2(2), TP53(74), TWIST1(1) 7247552 444 223 300 50 87 115 119 6 99 18 3.94e-10 <1.00e-15 <1.31e-14
2 MTORPATHWAY Mammalian target of rapamycin (mTOR) senses mitogenic factors and nutrients, including ATP, and induces cell proliferation. AKT1, EIF3S10, EIF4A1, EIF4A2, EIF4B, EIF4E, EIF4EBP1, EIF4G1, EIF4G2, EIF4G3, FKBP1A, FRAP1, MKNK1, PDK2, PDPK1, PIK3CA, PIK3R1, PPP2CA, PTEN, RPS6, RPS6KB1, TSC1, TSC2 21 AKT1(4), EIF4A1(5), EIF4A2(9), EIF4B(7), EIF4E(2), EIF4G1(15), EIF4G2(7), EIF4G3(24), FKBP1A(1), MKNK1(3), PDK2(5), PDPK1(3), PIK3CA(172), PIK3R1(100), PPP2CA(6), PTEN(227), RPS6(7), RPS6KB1(5), TSC1(13), TSC2(15) 10458408 630 218 417 44 90 141 126 38 191 44 <1.00e-15 <1.00e-15 <1.31e-14
3 IGF1MTORPATHWAY Growth factor IGF-1 activates AKT, Gsk3-beta, and mTOR to promote muscle hypertrophy. AKT1, EIF2B5, EIF2S1, EIF2S2, EIF2S3, EIF4E, EIF4EBP1, FRAP1, GSK3B, IGF1, IGF1R, INPPL1, PDK2, PDPK1, PIK3CA, PIK3R1, PPP2CA, PTEN, RPS6, RPS6KB1 19 AKT1(4), EIF2B5(5), EIF2S1(2), EIF2S2(9), EIF2S3(6), EIF4E(2), GSK3B(13), IGF1(5), IGF1R(13), INPPL1(19), PDK2(5), PDPK1(3), PIK3CA(172), PIK3R1(100), PPP2CA(6), PTEN(227), RPS6(7), RPS6KB1(5) 7335096 603 217 388 46 79 131 117 40 194 42 <1.00e-15 <1.00e-15 <1.31e-14
4 METPATHWAY The hepatocyte growth factor receptor c-Met stimulates proliferation and alters cell motility and adhesion on binding the ligand HGF. ACTA1, CRK, CRKL, DOCK1, ELK1, FOS, GAB1, GRB2, GRF2, HGF, HRAS, ITGA1, ITGB1, JUN, MAP2K1, MAP2K2, MAP4K1, MAPK1, MAPK3, MAPK8, MET, PAK1, PIK3CA, PIK3R1, PTEN, PTK2, PTK2B, PTPN11, PXN, RAF1, RAP1A, RAP1B, RASA1, SOS1, SRC, STAT3 35 ACTA1(5), CRK(2), CRKL(6), DOCK1(24), ELK1(3), FOS(3), GAB1(8), GRB2(3), HGF(14), HRAS(1), ITGA1(17), ITGB1(8), JUN(1), MAP2K1(2), MAP2K2(5), MAP4K1(11), MAPK1(2), MAPK3(3), MAPK8(10), MET(17), PAK1(3), PIK3CA(172), PIK3R1(100), PTEN(227), PTK2(12), PTK2B(16), PTPN11(8), PXN(6), RAF1(8), RAP1A(4), RAP1B(2), RASA1(30), SOS1(13), SRC(3), STAT3(10) 17110264 759 217 538 93 134 188 148 37 208 44 3.89e-15 <1.00e-15 <1.31e-14
5 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 47 AKT1(4), AKT2(6), AKT3(11), BRD4(10), CAP1(7), CBL(12), CDC42(4), CDKN2A(2), F2RL2(2), FLOT2(2), GRB2(3), GSK3A(10), GSK3B(13), IGFBP1(4), INPPL1(19), IRS1(13), IRS4(21), LNPEP(10), MAPK1(2), MAPK3(3), PARD3(19), PDK1(2), PIK3CA(172), PIK3CD(12), PIK3R1(100), PPYR1(8), PTEN(227), PTPN1(5), RAF1(8), RPS6KA1(1), RPS6KA2(14), RPS6KA3(19), RPS6KB1(5), SERPINB6(3), SHC1(7), SLC2A4(9), SORBS1(18), SOS1(13), SOS2(17), YWHAE(4), YWHAG(3), YWHAH(3), YWHAQ(1), YWHAZ(1) 21082232 829 217 605 120 160 197 174 40 214 44 5.04e-12 <1.00e-15 <1.31e-14
6 EIF4PATHWAY The eIF-4F complex recognizes 5' mRNA caps, recruits RNA helicases, and maintains mRNA-ribosome bridging. AKT1, EIF4A1, EIF4A2, EIF4E, EIF4EBP1, EIF4G1, EIF4G2, EIF4G3, FRAP1, GHR, IRS1, MAPK1, MAPK14, MAPK3, MKNK1, PABPC1, PDK2, PDPK1, PIK3CA, PIK3R1, PRKCA, PRKCB1, PTEN, RPS6KB1 22 AKT1(4), EIF4A1(5), EIF4A2(9), EIF4E(2), EIF4G1(15), EIF4G2(7), EIF4G3(24), GHR(8), IRS1(13), MAPK1(2), MAPK14(4), MAPK3(3), MKNK1(3), PABPC1(11), PDK2(5), PDPK1(3), PIK3CA(172), PIK3R1(100), PRKCA(10), PTEN(227), RPS6KB1(5) 10435840 632 216 418 49 91 134 133 39 191 44 <1.00e-15 <1.00e-15 <1.31e-14
7 SIG_PIP3_SIGNALING_IN_CARDIAC_MYOCTES Genes related to PIP3 signaling in cardiac myocytes AKT1, AKT2, AKT3, BAD, BCL2L1, CDC42, CDK2, CDKN1B, CDKN2A, CREB1, CREB3, CREB5, EBP, ERBB4, F2RL2, FOXO3A, FRAP1, GAB1, GADD45A, GRB2, GSK3A, GSK3B, IFI27, IGF1, IGFBP1, INPPL1, IRS1, IRS2, IRS4, MET, MYC, NOLC1, P101-PI3K, PAK1, PAK2, PAK3, PAK4, PAK6, PAK7, PARD3, PARD6A, PDK1, PIK3CA, PIK3CD, PPP1R13B, PREX1, PSCD3, PTEN, PTK2, PTPN1, RPS6KA1, RPS6KA2, RPS6KA3, RPS6KB1, SFN, SHC1, SLC2A4, SOS1, SOS2, TSC1, TSC2, YWHAB, YWHAE, YWHAG, YWHAH, YWHAQ, YWHAZ 62 AKT1(4), AKT2(6), AKT3(11), BAD(2), BCL2L1(4), CDC42(4), CDK2(2), CDKN1B(7), CDKN2A(2), CREB1(6), CREB5(5), EBP(2), ERBB4(27), F2RL2(2), GAB1(8), GRB2(3), GSK3A(10), GSK3B(13), IGF1(5), IGFBP1(4), INPPL1(19), IRS1(13), IRS4(21), MET(17), MYC(8), NOLC1(14), PAK1(3), PAK2(3), PAK3(17), PAK6(4), PAK7(9), PARD3(19), PDK1(2), PIK3CA(172), PIK3CD(12), PPP1R13B(9), PREX1(25), PTEN(227), PTK2(12), PTPN1(5), RPS6KA1(1), RPS6KA2(14), RPS6KA3(19), RPS6KB1(5), SHC1(7), SLC2A4(9), SOS1(13), SOS2(17), TSC1(13), TSC2(15), YWHAE(4), YWHAG(3), YWHAH(3), YWHAQ(1), YWHAZ(1) 27949352 863 216 660 148 188 253 185 41 166 30 9.72e-12 <1.00e-15 <1.31e-14
8 PTENPATHWAY PTEN suppresses AKT-induced cell proliferation and antagonizes the action of PI3K. AKT1, BCAR1, CDKN1B, FOXO3A, GRB2, ILK, ITGB1, MAPK1, MAPK3, PDK2, PDPK1, PIK3CA, PIK3R1, PTEN, PTK2, SHC1, SOS1, TNFSF6 16 AKT1(4), BCAR1(8), CDKN1B(7), GRB2(3), ILK(5), ITGB1(8), MAPK1(2), MAPK3(3), PDK2(5), PDPK1(3), PIK3CA(172), PIK3R1(100), PTEN(227), PTK2(12), SHC1(7), SOS1(13) 7174392 579 213 364 30 72 121 124 37 183 42 <1.00e-15 <1.00e-15 <1.31e-14
9 SIG_PIP3_SIGNALING_IN_B_LYMPHOCYTES Genes related to PIP3 signaling in B lymphocytes AKT1, AKT2, AKT3, BCR, BTK, CD19, CDKN2A, DAPP1, FLOT1, FLOT2, FOXO3A, GAB1, ITPR1, ITPR2, ITPR3, LYN, NR0B2, P101-PI3K, PDK1, PHF11, PIK3CA, PITX2, PLCG2, PPP1R13B, PREX1, PSCD3, PTEN, PTPRC, RPS6KA1, RPS6KA2, RPS6KA3, RPS6KB1, SAG, SYK, TEC, VAV1 32 AKT1(4), AKT2(6), AKT3(11), BCR(6), BTK(12), CD19(4), CDKN2A(2), DAPP1(9), FLOT2(2), GAB1(8), ITPR1(36), ITPR2(35), ITPR3(21), LYN(9), NR0B2(2), PDK1(2), PHF11(5), PIK3CA(172), PITX2(12), PLCG2(29), PPP1R13B(9), PREX1(25), PTEN(227), PTPRC(17), RPS6KA1(1), RPS6KA2(14), RPS6KA3(19), RPS6KB1(5), SAG(10), SYK(4), TEC(8), VAV1(12) 20541344 738 212 540 128 147 231 144 38 149 29 5.04e-10 <1.00e-15 <1.31e-14
10 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(3), AKT1(4), AKT2(6), AKT3(11), BAD(2), BTK(12), CDKN2A(2), DAPP1(9), GRB2(3), GSK3A(10), GSK3B(13), IARS(8), IGFBP1(4), INPP5D(9), PDK1(2), PIK3CA(172), PPP1R13B(9), PTEN(227), RPS6KA1(1), RPS6KA2(14), RPS6KA3(19), RPS6KB1(5), SHC1(7), SOS1(13), SOS2(17), TEC(8), YWHAE(4), YWHAG(3), YWHAH(3), YWHAQ(1), YWHAZ(1) 13352320 602 211 404 65 112 161 131 37 133 28 1.22e-15 <1.00e-15 <1.31e-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_ns_s p q
1 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 CD2(4), CD34(1), CD3D(6), CD3E(2), CD3G(3), CD4(6), CD58(2), CD8A(2), CSF3(1), IL3(2), IL6(5), IL8(3), KITLG(3) 2324752 40 27 40 9 6 20 4 0 10 0 0.18 0.063 1
2 VOBESITYPATHWAY The adipose tissue of obese individuals overexpresses a key glucocorticoid-metabolizing enzyme, activating inactive circulating corticosteroids and inducing insulin resistance. APM1, HSD11B1, LPL, NR3C1, PPARG, RETN, RXRA, TNF 7 HSD11B1(6), LPL(16), NR3C1(18), PPARG(6), RETN(1), RXRA(3) 2006320 50 24 49 9 12 20 7 1 10 0 0.027 0.11 1
3 TCRMOLECULE T Cell Receptor and CD3 Complex CD3D, CD3E, CD3G, CD3Z, TRA@, TRB@ 3 CD3D(6), CD3E(2), CD3G(3) 437720 11 7 11 1 1 7 0 0 3 0 0.18 0.13 1
4 HSA00627_1,4_DICHLOROBENZENE_DEGRADATION Genes involved in 1,4-dichlorobenzene degradation CMBL 1 CMBL(3) 187984 3 3 3 1 0 1 0 1 1 0 0.81 0.14 1
5 HSA00031_INOSITOL_METABOLISM Genes involved in inositol metabolism ALDH6A1, TPI1 2 ALDH6A1(6), TPI1(2) 594208 8 7 8 1 0 3 1 0 4 0 0.28 0.17 1
6 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 ARNT(5), ASPH(13), COPS5(5), CREB1(6), EDN1(4), EP300(32), EPO(2), HIF1A(16), JUN(1), LDHA(8), NOS3(11), P4HB(6), VHL(3) 6388976 112 46 111 16 32 32 26 2 20 0 0.00048 0.22 1
7 IL5PATHWAY Pro-inflammatory IL-5 is secretes by activated T cells, eosinophils, and mast cells, and stimulates the proliferation and activation of eosinophils in bone marrow. CCL11, CCR3, CD4, HLA-DRA, HLA-DRB1, IL1B, IL4, IL5, IL5RA, IL6 9 CCR3(4), CD4(6), IL1B(2), IL4(1), IL5(2), IL5RA(9), IL6(5) 1760056 29 21 27 8 3 13 3 0 10 0 0.31 0.22 1
8 PEPIPATHWAY Proepithelin (PEPI) induces epithelial cells to secrete IL-8, which promotes elastase secretion by neutrophils. ELA1, ELA2, ELA2A, ELA2B, ELA3B, GRN, IL8, SLPI 3 GRN(5), IL8(3), SLPI(2) 635128 10 10 9 0 2 5 2 0 1 0 0.057 0.25 1
9 LDLPATHWAY Low density lipoproteins (LDL) are present in blood plasma, contain cholesterol and triglycerides, and contribute to atherogenic plaque formation. ACAT1, CCL2, CSF1, IL6, LDLR, LPL 6 ACAT1(6), CSF1(6), IL6(5), LDLR(6), LPL(16) 1950272 39 23 39 7 10 15 9 0 5 0 0.057 0.3 1
10 TCAPOPTOSISPATHWAY HIV infection upregulates Fas ligand in macrophages and CD4 in helper T cells, leading to widespread Fas-induced T cell apoptosis. CCR5, CD28, CD3D, CD3E, CD3G, CD3Z, CD4, TNFRSF6, TNFSF6, TRA@, TRB@ 6 CCR5(6), CD28(3), CD3D(6), CD3E(2), CD3G(3), CD4(6) 1218920 26 16 26 6 3 16 0 0 7 0 0.26 0.31 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 Ð 615 (2011)
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