Uterine Corpus Endometrioid Carcinoma: 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: UCEC-TP

  • 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

  • MAF used for this analysis:UCEC-TP.final_analysis_set.maf

  • Significantly mutated genes (q ≤ 0.1): 36

  • Mutations seen in COSMIC: 1007

  • Significantly mutated genes in COSMIC territory: 47

  • Genes with clustered mutations (≤ 3 aa apart): 4496

  • Significantly mutated genesets: 68

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

Mutation Preprocessing

  • Read 248 MAFs of type "WashU"

  • Total number of mutations in input MAFs: 184824

  • After removing 118 mutations outside chr1-24: 184706

  • After removing 211 blacklisted mutations: 184495

  • After removing 1932 noncoding mutations: 182563

  • After collapsing adjacent/redundant mutations: 182433

Mutation Filtering

  • Number of mutations before filtering: 182433

  • After removing 8662 mutations outside gene set: 173771

  • After removing 1038 mutations outside category set: 172733

Results
Breakdown of Mutations by Type

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

type count
Frame_Shift_Del 1059
Frame_Shift_Ins 461
In_Frame_Del 710
In_Frame_Ins 136
Missense_Mutation 115564
Nonsense_Mutation 11935
Nonstop_Mutation 138
Silent 40083
Splice_Site 2647
Total 172733
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 38697 409266464 0.000095 95 5.4 2.1
*Cp(A/C/T)->mut 51438 3453658664 0.000015 15 0.85 3.3
A->mut 24335 3744388816 6.5e-06 6.5 0.37 3.9
*CpG->(G/A) 1084 409266464 2.6e-06 2.6 0.15 2.7
indel+null 16212 7607313944 2.1e-06 2.1 0.12 NaN
double_null 884 7607313944 1.2e-07 0.12 0.0067 NaN
Total 132650 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.  Patients counts and rates file used to generate this plot: UCEC-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_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: 36. 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 PTEN phosphatase and tensin homolog (mutated in multiple advanced cancers 1) 309504 227 161 134 5 19 29 21 33 98 27 <1.00e-15 4.9e-12 NaN NaN <1.00e-15 <3.66e-12
2 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 815176 172 132 76 3 31 61 68 3 9 0 <1.00e-15 2.1e-11 NaN NaN <1.00e-15 <3.66e-12
3 ARID1A AT rich interactive domain 1A (SWI-like) 1428976 93 83 78 5 2 7 5 1 64 14 <1.00e-15 0.00014 NaN NaN <1.00e-15 <3.66e-12
4 TP53 tumor protein p53 317688 74 69 50 2 23 18 15 1 17 0 <1.00e-15 2.8e-06 NaN NaN <1.00e-15 <3.66e-12
5 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 <1.00e-15 0.0097 NaN NaN <1.00e-15 <3.66e-12
6 CTCF CCCTC-binding factor (zinc finger protein) 551552 49 45 39 1 8 4 7 0 28 2 1.55e-15 0.00095 NaN NaN 1.55e-15 4.74e-12
7 PIK3R1 phosphoinositide-3-kinase, regulatory subunit 1 (alpha) 585280 100 83 77 2 4 4 13 1 63 15 1.89e-15 0.0021 NaN NaN 1.89e-15 4.82e-12
8 KRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog 175336 53 53 12 1 2 46 4 1 0 0 2.11e-15 0.0012 NaN NaN 2.11e-15 4.82e-12
9 CTNNB1 catenin (cadherin-associated protein), beta 1, 88kDa 595696 80 74 25 7 5 61 14 0 0 0 4.11e-15 0.0034 NaN NaN 4.11e-15 8.35e-12
10 FBXW7 F-box and WD repeat domain containing 7 640832 46 39 30 1 22 12 2 1 8 1 4.88e-15 0.00048 NaN NaN 4.88e-15 8.93e-12
11 SPOP speckle-type POZ protein 287928 23 21 18 0 5 8 6 0 4 0 1.28e-14 0.0041 NaN NaN 1.28e-14 2.12e-11
12 PPP2R1A protein phosphatase 2 (formerly 2A), regulatory subunit A , alpha isoform 453840 30 27 18 3 10 17 1 0 2 0 5.75e-14 0.0023 NaN NaN 5.75e-14 8.76e-11
13 CHD4 chromodomain helicase DNA binding protein 4 1460720 43 35 38 2 16 16 8 0 2 1 1.45e-11 0.0046 NaN NaN 1.45e-11 2.05e-08
14 P2RY11 purinergic receptor P2Y, G-protein coupled, 11 5704 9 9 9 3 3 4 0 1 1 0 2.14e-11 0.3 NaN NaN 2.14e-11 2.79e-08
15 CCND1 cyclin D1 222952 15 15 13 1 1 7 3 0 4 0 7.28e-09 0.084 NaN NaN 7.28e-09 8.87e-06
16 NFE2L2 nuclear factor (erythroid-derived 2)-like 2 449872 15 15 12 0 2 3 5 3 2 0 2.69e-08 0.016 NaN NaN 2.69e-08 3.07e-05
17 FOXA2 forkhead box A2 227912 12 12 12 1 1 3 2 0 6 0 3.43e-08 0.27 NaN NaN 3.43e-08 3.69e-05
18 FAM9A family with sequence similarity 9, member A 255688 20 14 20 1 2 12 1 0 4 1 7.26e-08 0.096 NaN NaN 7.26e-08 7.38e-05
19 SOX17 SRY (sex determining region Y)-box 17 91512 7 7 3 0 0 6 0 0 1 0 4.29e-07 0.15 NaN NaN 4.29e-07 0.000412
20 ZNF267 zinc finger protein 267 557504 22 16 19 1 10 5 3 1 3 0 1.16e-05 0.13 NaN NaN 1.16e-05 0.0105
21 MAX MYC associated factor X 209064 12 11 8 0 3 3 5 0 1 0 1.20e-05 0.048 NaN NaN 1.20e-05 0.0105
22 CYLC1 cylicin, basic protein of sperm head cytoskeleton 1 490048 27 18 27 2 0 16 7 0 4 0 2.06e-05 0.13 NaN NaN 2.06e-05 0.0171
23 RBMX RNA binding motif protein, X-linked 313224 14 13 8 0 1 4 2 0 7 0 2.77e-05 0.3 NaN NaN 2.77e-05 0.0220
24 MORC4 MORC family CW-type zinc finger 4 685472 28 20 26 2 6 10 1 0 11 0 4.53e-05 0.083 NaN NaN 4.53e-05 0.0340
25 OR4K2 olfactory receptor, family 4, subfamily K, member 2 235352 12 11 12 0 1 8 3 0 0 0 4.65e-05 0.028 NaN NaN 4.65e-05 0.0340
26 ARID5B AT rich interactive domain 5B (MRF1-like) 894536 34 29 34 9 5 5 8 2 13 1 5.47e-05 0.57 NaN NaN 5.47e-05 0.0385
27 OR5D13 olfactory receptor, family 5, subfamily D, member 13 235104 10 10 9 0 2 4 2 0 2 0 6.69e-05 0.06 NaN NaN 6.69e-05 0.0453
28 OR5AS1 olfactory receptor, family 5, subfamily AS, member 1 242296 12 10 12 1 1 7 4 0 0 0 6.96e-05 0.15 NaN NaN 6.96e-05 0.0454
29 OR4A15 olfactory receptor, family 4, subfamily A, member 15 257424 16 13 16 1 1 10 5 0 0 0 0.000103 0.065 NaN NaN 0.000103 0.0652
30 CSDE1 cold shock domain containing E1, RNA-binding 647528 32 21 28 3 12 9 5 1 5 0 0.000112 0.066 NaN NaN 0.000112 0.0679
31 CTXN3 cortexin 3 62000 6 6 6 0 1 4 0 1 0 0 0.000117 0.21 NaN NaN 0.000117 0.0679
32 PAPD4 PAP associated domain containing 4 374728 13 13 13 1 3 5 3 0 2 0 0.000119 0.26 NaN NaN 0.000119 0.0679
33 RPL14 ribosomal protein L14 168392 8 7 4 0 0 1 0 2 5 0 0.000144 0.36 NaN NaN 0.000144 0.0799
34 DNER delta/notch-like EGF repeat containing 492528 21 18 20 1 4 9 5 0 3 0 0.000155 0.01 NaN NaN 0.000155 0.0835
35 TAB3 TGF-beta activated kinase 1/MAP3K7 binding protein 3 537416 21 18 21 2 2 11 4 0 3 1 0.000171 0.18 NaN NaN 0.000171 0.0877
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 53 52 49 12896 556649 0 0
3 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 172 220 150 54560 35669 0 0
4 CTNNB1 catenin (cadherin-associated protein), beta 1, 88kDa 80 138 67 34224 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 51 24 12648 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) 227 767 218 190216 14940 0 0
8 TP53 tumor protein p53 74 356 72 88288 24186 0 0
9 NRAS neuroblastoma RAS viral (v-ras) oncogene homolog 9 33 6 8184 6490 1e-08 5.2e-06
10 RB1 retinoblastoma 1 (including osteosarcoma) 26 267 11 66216 30 4.2e-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
11544 PTEN phosphatase and tensin homolog (mutated in multiple advanced cancers 1) 226 0 1515 1989 2858 1515 1989 2858
7586 KRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog 52 0 661 949 994 661 949 994
10787 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 172 0 573 1075 1553 573 1075 1553
3512 CTNNB1 catenin (cadherin-associated protein), beta 1, 88kDa 80 0 434 1165 2176 434 1165 2176
14922 TP53 tumor protein p53 74 0 89 167 417 89 167 417
5239 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
5150 FBXW7 F-box and WD repeat domain containing 7 46 0 50 53 68 50 53 68
11056 POLE polymerase (DNA directed), epsilon 47 0 39 42 60 39 42 60
11226 PPP2R1A protein phosphatase 2 (formerly 2A), regulatory subunit A , alpha isoform 30 0 37 48 77 37 48 77
15258 TTN titin 523 0 35 53 102 35 53 102

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: 68. 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 <4.11e-14
2 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 <4.11e-14
3 GSK3PATHWAY Bacterial lipopolysaccharide activates AKT to promote the survival and activation of macrophages and inhibits Gsk3-beta to promote beta-catenin accumulation in the nucleus. AKT1, APC, AXIN1, CCND1, CD14, CTNNB1, DVL1, FZD1, GJA1, GNAI1, GSK3B, IRAK1, LBP, LEF1, LY96, MYD88, NFKB1, PDPK1, PIK3CA, PIK3R1, PPP2CA, PRKR, RELA, TIRAP, TLR4, TOLLIP, WNT1 26 AKT1(4), APC(56), AXIN1(9), CCND1(15), CD14(2), CTNNB1(80), DVL1(3), FZD1(3), GJA1(5), GNAI1(5), GSK3B(13), IRAK1(4), LBP(3), LEF1(9), LY96(4), MYD88(3), NFKB1(10), PDPK1(3), PIK3CA(172), PIK3R1(100), PPP2CA(6), RELA(6), TIRAP(2), TLR4(17), TOLLIP(1), WNT1(1) 11218032 536 210 356 58 77 201 122 6 110 20 9.76e-14 <1.00e-15 <4.11e-14
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(4), AKT2(6), AKT3(11), BPNT1(3), GRB2(3), ILK(5), MAPK1(2), MAPK3(3), PDK1(2), PIK3CA(172), PIK3CD(12), PTEN(227), PTK2B(16), RBL2(19), SHC1(7), SOS1(13) 7530768 505 208 307 39 91 126 107 36 117 28 <1.00e-15 <1.00e-15 <4.11e-14
5 HDACPATHWAY Myocyte enhancer factor MEF2 activates transcription of genes required for muscle cell differentiation and is inhibited by histone deacetylases. AKT1, AVP, CABIN1, CALM1, CALM2, CALM3, CAMK1, CAMK1G, HDAC5, IGF1, IGF1R, INS, INSR, MAP2K6, MAPK14, MAPK7, MEF2A, MEF2B, MEF2C, MEF2D, MYOD1, NFATC1, NFATC2, PIK3CA, PIK3R1, PPP3CA, PPP3CB, PPP3CC, SYT1, YWHAH 28 AKT1(4), CABIN1(19), CALM1(2), CALM2(4), CAMK1(2), CAMK1G(5), HDAC5(12), IGF1(5), IGF1R(13), INS(3), INSR(18), MAP2K6(10), MAPK14(4), MAPK7(14), MEF2A(3), MEF2B(1), MEF2C(11), MEF2D(7), NFATC1(10), NFATC2(13), PIK3CA(172), PIK3R1(100), PPP3CA(4), PPP3CB(5), PPP3CC(6), SYT1(4), YWHAH(3) 12782416 454 202 331 71 109 116 116 8 90 15 1.34e-07 <1.00e-15 <4.11e-14
6 INSULINPATHWAY Insulin regulates glucose levels via Ras-mediated transcriptional activation. CSNK2A1, ELK1, FOS, GRB2, HRAS, INS, INSR, IRS1, JUN, MAP2K1, MAPK3, MAPK8, PIK3CA, PIK3R1, PTPN11, RAF1, RASA1, SHC1, SLC2A4, SOS1, SRF 21 CSNK2A1(9), ELK1(3), FOS(3), GRB2(3), HRAS(1), INS(3), INSR(18), IRS1(13), JUN(1), MAP2K1(2), MAPK3(3), MAPK8(10), PIK3CA(172), PIK3R1(100), PTPN11(8), RAF1(8), RASA1(30), SHC1(7), SLC2A4(9), SOS1(13), SRF(3) 9476328 419 202 292 39 82 118 108 5 90 16 2.40e-13 <1.00e-15 <4.11e-14
7 SIG_IL4RECEPTOR_IN_B_LYPHOCYTES Genes related to IL4 rceptor signaling in B lymphocytes AKT1, AKT2, AKT3, BAD, BCL2, GRB2, GSK3A, GSK3B, IL4R, IRS1, IRS2, JAK1, JAK3, MAP4K1, MAPK1, MAPK3, PDK1, PIK3CA, PIK3CD, PIK3R1, PPP1R13B, RAF1, SHC1, SOCS1, SOS1, SOS2, STAT6 25 AKT1(4), AKT2(6), AKT3(11), BAD(2), GRB2(3), GSK3A(10), GSK3B(13), IL4R(6), IRS1(13), JAK1(20), JAK3(10), MAP4K1(11), MAPK1(2), MAPK3(3), PDK1(2), PIK3CA(172), PIK3CD(12), PIK3R1(100), PPP1R13B(9), RAF1(8), SHC1(7), SOS1(13), SOS2(17), STAT6(10) 13137552 464 202 337 55 106 123 119 5 95 16 8.06e-11 <1.00e-15 <4.11e-14
8 GLEEVECPATHWAY The drug Gleevec specifically targets the abnormal bcr-abl protein, an apoptosis inhibitor present in chronic myeloid leukemia. AKT1, BCL2, BCR, CRKL, FOS, GRB2, HRAS, JAK2, JUN, MAP2K1, MAP2K4, MAP3K1, MAPK3, MAPK8, MYC, PIK3CA, PIK3R1, RAF1, SOS1, STAT1, STAT5A, STAT5B 22 AKT1(4), BCR(6), CRKL(6), FOS(3), GRB2(3), HRAS(1), JAK2(17), JUN(1), MAP2K1(2), MAP2K4(9), MAP3K1(30), MAPK3(3), MAPK8(10), MYC(8), PIK3CA(172), PIK3R1(100), RAF1(8), SOS1(13), STAT1(15), STAT5A(5), STAT5B(7) 10234960 423 199 298 39 75 122 113 4 90 19 9.63e-13 <1.00e-15 <4.11e-14
9 IGF1RPATHWAY Insulin-like growth factor receptor IGF-1R promotes cell growth and inhibits apoptosis on binding of ligands IGF-1 and 2 via Ras activation and the AKT pathway. AKT1, BAD, GRB2, HRAS, IGF1R, IRS1, MAP2K1, MAPK1, MAPK3, PIK3CA, PIK3R1, RAF1, SHC1, SOS1, YWHAH 15 AKT1(4), BAD(2), GRB2(3), HRAS(1), IGF1R(13), IRS1(13), MAP2K1(2), MAPK1(2), MAPK3(3), PIK3CA(172), PIK3R1(100), RAF1(8), SHC1(7), SOS1(13), YWHAH(3) 6997568 346 196 223 34 62 91 97 5 76 15 3.14e-09 <1.00e-15 <4.11e-14
10 NKCELLSPATHWAY Natural killer (NK) lymphocytes are inhibited by MHC and activated by surface glycoproteins on tumor or virus-infected cells, which undergo perforin-mediated lysis. B2M, HLA-A, IL18, ITGB1, KLRC1, KLRC2, KLRC3, KLRC4, KLRD1, LAT, MAP2K1, MAPK3, PAK1, PIK3CA, PIK3R1, PTK2B, PTPN6, RAC1, SYK, VAV1 20 B2M(3), HLA-A(1), IL18(2), ITGB1(8), KLRC1(7), KLRC2(3), KLRC3(1), KLRC4(5), KLRD1(3), MAP2K1(2), MAPK3(3), PAK1(3), PIK3CA(172), PIK3R1(100), PTK2B(16), PTPN6(6), RAC1(1), SYK(4), VAV1(12) 7058328 352 196 232 34 59 99 93 5 81 15 1.94e-09 <1.00e-15 <4.11e-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 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 0.18 1
2 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 5 3 16 0 0 7 0 0.16 0.2 1
3 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 0.31 1
4 HSA00472_D_ARGININE_AND_D_ORNITHINE_METABOLISM Genes involved in D-arginine and D-ornithine metabolism DAO 1 DAO(8) 268832 8 6 8 1 2 4 2 0 0 0 0.3 0.32 1
5 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 0.41 1
6 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 0.41 1
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 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 0.42 1
8 P27PATHWAY p27 blocks the G1/S transition by inhibiting the checkpoint kinase cdk2/cyclin E and is inhibited by cdk2-mediated ubiquitination. CCNE1, CDK2, CDKN1B, CKS1B, CUL1, E2F1, NEDD8, RB1, RBX1, SKP1A, SKP2, TFDP1, UBE2M 12 CCNE1(6), CDK2(2), CDKN1B(7), CKS1B(1), CUL1(13), E2F1(9), RB1(26), RBX1(1), SKP2(7), TFDP1(13) 3255992 85 39 83 17 27 25 17 0 13 3 0.027 0.42 1
9 HSA00643_STYRENE_DEGRADATION Genes involved in styrene degradation FAH, GSTZ1, HGD 3 FAH(6), GSTZ1(5), HGD(4) 842456 15 12 15 2 5 4 4 0 2 0 0.11 0.48 1
10 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 0.56 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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