Breast Invasive 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: BRCA

  • Number of patients in set: 507

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:BRCA.final_analysis_set.maf

  • Significantly mutated genes (q ≤ 0.1): 41

  • Mutations seen in COSMIC: 500

  • Significantly mutated genes in COSMIC territory: 16

  • Genes with clustered mutations (≤ 3 aa apart): 273

  • Significantly mutated genesets: 115

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

Mutation Preprocessing

  • Read 507 MAFs of type "WashU"

  • Total number of mutations in input MAFs: 33982

  • After removing 41 mutations outside chr1-24: 33941

  • After removing 1665 noncoding mutations: 32276

  • After collapsing adjacent/redundant mutations: 31999

Mutation Filtering

  • Number of mutations before filtering: 31999

  • After removing 1528 mutations outside gene set: 30471

  • After removing 148 mutations outside category set: 30323

Results
Breakdown of Mutations by Type

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

type count
Frame_Shift_Del 958
Frame_Shift_Ins 311
In_Frame_Del 388
In_Frame_Ins 74
Missense_Mutation 19287
Nonsense_Mutation 1398
Nonstop_Mutation 34
Silent 7287
Splice_Site 586
Total 30323
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 3903 836685876 4.7e-06 4.7 3.1 2.1
*Cp(A/C/T)->T 4294 7060503801 6.1e-07 0.61 0.41 1.7
C->(G/A) 6959 7897189677 8.8e-07 0.88 0.59 4.8
A->mut 4125 7654859394 5.4e-07 0.54 0.36 3.9
indel+null 3696 15552049071 2.4e-07 0.24 0.16 NaN
double_null 59 15552049071 3.8e-09 0.0038 0.0026 NaN
Total 23036 15552049071 1.5e-06 1.5 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: BRCA.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)->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

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

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

  • p_joint = p-value for clustering + conservation

  • p = p-value (overall)

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

Table 3.  Get Full Table A Ranked List of Significantly Mutated Genes. Number of significant genes found: 41. 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_ks p_cons p_joint p q
1 RUNX1 runt-related transcription factor 1 (acute myeloid leukemia 1; aml1 oncogene) 630708 18 18 17 1 0 2 1 3 12 0 7.99e-15 0.225 0.00023 0.26 0.00047 1.11e-16 2.03e-12
2 MAP2K4 mitogen-activated protein kinase kinase 4 570375 20 20 19 0 3 2 2 1 12 0 3.66e-15 0.0346 0.0077 0.042 0.0071 9.99e-16 2.29e-12
3 TP53 tumor protein p53 649467 187 184 113 3 29 23 23 39 73 0 <1.00e-15 3.33e-15 2e-07 2e-07 0 <1.00e-15 <2.29e-12
4 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 1666509 194 178 32 3 3 70 8 105 8 0 <1.00e-15 <1.00e-15 2e-07 2e-07 0 <1.00e-15 <2.29e-12
5 GATA3 GATA binding protein 3 574431 56 54 34 1 0 1 0 3 51 1 1.44e-15 0.519 2e-07 0.058 0 <1.00e-15 <2.29e-12
6 AKT1 v-akt murine thymoma viral oncogene homolog 1 757965 12 12 2 1 0 11 0 1 0 0 3.23e-10 0.00521 2e-07 0.000036 0 <1.00e-15 <2.29e-12
7 OR10J5 olfactory receptor, family 10, subfamily J, member 5 472524 2 2 2 0 1 1 0 0 0 0 0.0294 0.415 0.023 0.0015 0 <1.00e-15 <2.29e-12
8 ZNF283 zinc finger protein 283 978003 2 2 2 0 0 0 0 1 1 0 0.313 0.586 0.022 0.0013 0 <1.00e-15 <2.29e-12
9 CDH1 cadherin 1, type 1, E-cadherin (epithelial) 1347099 33 33 30 1 0 3 1 0 29 0 3.00e-15 0.0312 0.2 0.33 0.24 2.53e-14 5.14e-11
10 MAP3K1 mitogen-activated protein kinase kinase kinase 1 2095431 46 38 45 3 0 0 2 5 24 15 5.66e-15 0.271 0.4 0.092 0.25 4.93e-14 9.01e-11
11 PIK3R1 phosphoinositide-3-kinase, regulatory subunit 1 (alpha) 1196520 14 14 13 1 0 2 2 1 9 0 7.16e-11 0.610 0.000011 0.11 0.000025 6.21e-14 9.66e-11
12 PTEN phosphatase and tensin homolog (mutated in multiple advanced cancers 1) 632736 17 17 16 0 1 0 2 2 11 1 1.40e-14 0.181 0.082 0.3 0.13 6.34e-14 9.66e-11
13 TBX3 T-box 3 (ulnar mammary syndrome) 709800 13 13 13 0 0 2 1 0 10 0 1.98e-11 0.176 0.00085 0.65 0.0019 1.21e-12 1.71e-09
14 MLL3 myeloid/lymphoid or mixed-lineage leukemia 3 7571538 38 37 38 2 0 8 4 3 23 0 8.82e-12 0.121 0.38 0.14 0.25 6.16e-11 8.04e-08
15 CBFB core-binding factor, beta subunit 246909 8 8 8 1 0 4 0 1 3 0 1.18e-10 0.339 0.14 0.066 0.1 3.15e-10 3.84e-07
16 CTCF CCCTC-binding factor (zinc finger protein) 1127568 13 13 11 2 1 1 2 2 7 0 1.24e-06 0.494 0.029 0.00038 0.00098 2.63e-08 3.00e-05
17 SF3B1 splicing factor 3b, subunit 1, 155kDa 2047773 10 10 6 0 0 1 0 8 1 0 0.000133 0.0496 0.000032 0.11 1e-05 2.85e-08 3.07e-05
18 FOXA1 forkhead box A1 603330 8 8 7 0 1 3 2 1 1 0 4.12e-06 0.0502 0.00025 0.26 0.0004 3.46e-08 3.51e-05
19 KLRG2 killer cell lectin-like receptor subfamily G, member 2 228150 3 3 1 0 0 0 3 0 0 0 0.00302 0.502 2.2e-06 0.41 1.4e-06 8.58e-08 8.26e-05
20 C9orf102 chromosome 9 open reading frame 102 1098162 5 5 3 1 0 3 0 2 0 0 0.00388 0.552 3e-06 1 9.6e-06 6.74e-07 0.000617
21 VASN vasorin 348309 6 6 3 0 0 0 1 4 1 0 5.59e-06 0.384 0.0067 0.9 0.017 1.61e-06 0.00140
22 C1orf65 chromosome 1 open reading frame 65 581529 7 7 5 0 1 4 1 1 0 0 2.27e-05 0.0373 0.0048 0.67 0.014 4.88e-06 0.00406
23 TBL1XR1 transducin (beta)-like 1 X-linked receptor 1 811707 8 8 7 0 0 0 1 1 4 2 7.32e-07 0.445 0.44 0.69 0.6 6.83e-06 0.00543
24 DALRD3 DALR anticodon binding domain containing 3 649467 6 6 6 0 1 0 2 0 3 0 0.000363 0.276 0.058 0.0024 0.0027 1.45e-05 0.0110
25 NCOR1 nuclear receptor co-repressor 1 3804021 17 17 17 1 0 1 1 1 13 1 2.70e-06 0.128 0.51 0.22 0.41 1.64e-05 0.0120
26 AFF2 AF4/FMR2 family, member 2 2066025 13 13 13 1 2 1 6 1 3 0 4.77e-06 0.235 0.14 0.68 0.25 1.75e-05 0.0123
27 ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian) 1902264 8 7 6 1 2 0 3 3 0 0 0.00982 0.391 0.00059 0.00072 0.00014 1.95e-05 0.0132
28 ZFP36L1 zinc finger protein 36, C3H type-like 1 519675 7 7 7 0 0 1 1 1 4 0 8.32e-06 0.305 0.073 0.91 0.17 2.08e-05 0.0136
29 GPS2 G protein pathway suppressor 2 518661 6 6 6 1 0 0 0 0 6 0 3.65e-05 0.921 0.037 0.08 0.044 2.31e-05 0.0146
30 MYB v-myb myeloblastosis viral oncogene homolog (avian) 1177761 8 8 8 0 1 1 1 1 4 0 6.64e-05 0.214 0.17 0.019 0.041 3.73e-05 0.0227
31 PRRX1 paired related homeobox 1 402051 5 5 5 0 3 0 1 0 1 0 0.000612 0.121 0.13 0.0044 0.0091 7.29e-05 0.0430
32 RPGR retinitis pigmentosa GTPase regulator 1930149 10 10 10 0 1 2 1 0 6 0 4.65e-05 0.271 0.32 0.062 0.14 8.40e-05 0.0480
33 CDKN1B cyclin-dependent kinase inhibitor 1B (p27, Kip1) 272259 5 5 4 0 0 0 0 0 5 0 2.47e-05 0.673 0.29 0.32 0.34 0.000106 0.0575
34 AVPI1 arginine vasopressin-induced 1 186069 4 4 3 0 1 0 3 0 0 0 0.000131 0.434 0.026 0.68 0.064 0.000107 0.0575
35 GPR32 G protein-coupled receptor 32 544518 5 5 3 1 1 0 1 3 0 0 0.000654 0.636 0.0057 0.81 0.016 0.000132 0.0689
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: 16. Number of genes displayed: 10

rank gene description n cos n_cos N_cos cos_ev p q
1 TP53 tumor protein p53 187 308 180 156156 37514 0 0
2 PIK3R1 phosphoinositide-3-kinase, regulatory subunit 1 (alpha) 14 33 7 16731 8 4.5e-13 6.9e-10
3 GATA3 GATA binding protein 3 56 34 21 17238 155 4.6e-13 6.9e-10
4 ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian) 8 41 6 20787 44 1.7e-12 1.4e-09
5 RUNX1 runt-related transcription factor 1 (acute myeloid leukemia 1; aml1 oncogene) 18 175 14 88725 54 2.1e-12 1.4e-09
6 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 194 184 184 93288 113646 2.2e-12 1.4e-09
7 CDH1 cadherin 1, type 1, E-cadherin (epithelial) 33 184 15 93288 27 2.2e-12 1.4e-09
8 PTEN phosphatase and tensin homolog (mutated in multiple advanced cancers 1) 17 728 17 369096 712 5.8e-12 3.3e-09
9 PTPN22 protein tyrosine phosphatase, non-receptor type 22 (lymphoid) 8 5 2 2535 2 7e-06 0.0035
10 FGFR2 fibroblast growth factor receptor 2 (bacteria-expressed kinase, keratinocyte growth factor receptor, craniofacial dysostosis 1, Crouzon syndrome, Pfeiffer syndrome, Jackson-Weiss syndrome) 4 49 3 24843 15 8.1e-06 0.0036

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
6944 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 194 0 4345 5558 5984 4345 5558 5984
9414 TP53 tumor protein p53 187 0 237 643 1330 237 643 1330
311 AKT1 v-akt murine thymoma viral oncogene homolog 1 12 0 55 55 55 55 55 55
8171 SF3B1 splicing factor 3b, subunit 1, 155kDa 10 0 10 10 10 10 10 10
6285 OBSCN obscurin, cytoskeletal calmodulin and titin-interacting RhoGEF 27 0 7 7 8 7 7 8
9873 VASN vasorin 6 0 6 6 6 6 6 6
1755 CDH1 cadherin 1, type 1, E-cadherin (epithelial) 33 0 5 5 6 5 5 6
2275 CTCF CCCTC-binding factor (zinc finger protein) 13 0 3 7 7 3 7 7
3858 GPR32 G protein-coupled receptor 32 5 0 3 4 4 3 4 4
3009 ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian) 8 0 3 3 4 3 3 4

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: 115. 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 HSA04210_APOPTOSIS Genes involved in apoptosis AIFM1, AKT1, AKT2, AKT3, APAF1, ATM, BAD, BAX, BCL2, BCL2L1, BID, BIRC2, BIRC3, BIRC4, CAPN1, CAPN2, CASP10, CASP3, CASP6, CASP7, CASP8, CASP9, CFLAR, CHP, CHUK, CSF2RB, CYCS, DFFA, DFFB, ENDOG, FADD, FAS, FASLG, IKBKB, IKBKG, IL1A, IL1B, IL1R1, IL1RAP, IL3, IL3RA, IRAK1, IRAK2, IRAK3, IRAK4, MAP3K14, MYD88, NFKB1, NFKB2, NFKBIA, NGFB, NTRK1, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PPP3CA, PPP3CB, PPP3CC, PPP3R1, PPP3R2, PRKACA, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, RELA, RIPK1, TNF, TNFRSF10A, TNFRSF10B, TNFRSF10C, TNFRSF10D, TNFRSF1A, TNFSF10, TP53, TRADD, TRAF2 81 AKT1(12), AKT2(1), AKT3(3), APAF1(1), ATM(12), BAD(1), BID(4), CAPN1(3), CAPN2(2), CASP6(2), CASP8(3), CSF2RB(2), DFFB(2), FAS(1), FASLG(1), IKBKB(3), IL1A(1), IL1R1(1), IL1RAP(2), IL3RA(1), IRAK1(1), IRAK2(3), IRAK3(1), IRAK4(2), NFKB1(1), NFKB2(3), NFKBIA(1), NTRK1(3), PIK3CA(194), PIK3CB(4), PIK3CG(2), PIK3R1(14), PIK3R3(1), PPP3CA(3), PPP3CB(3), PRKACA(1), PRKAR1A(1), PRKAR2A(1), PRKAR2B(1), RELA(1), RIPK1(3), TNFRSF10D(1), TNFRSF1A(1), TP53(187) 64465557 491 359 244 28 43 129 50 162 106 1 <1.00e-15 <1.00e-15 <1.43e-14
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(4), E2F1(2), MDM2(2), MYC(1), PIK3CA(194), PIK3R1(14), POLR1A(2), POLR1B(2), POLR1C(2), POLR1D(2), RB1(10), TP53(187) 14816568 422 334 185 11 35 97 37 151 102 0 <1.00e-15 <1.00e-15 <1.43e-14
3 HSA04620_TOLL_LIKE_RECEPTOR_SIGNALING_PATHWAY Genes involved in Toll-like receptor signaling pathway AKT1, AKT2, AKT3, CASP8, CCL3, CCL4, CCL5, CD14, CD40, CD80, CD86, CHUK, CXCL10, CXCL11, CXCL9, FADD, FOS, IFNA1, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA2, IFNA21, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNAR1, IFNAR2, IFNB1, IKBKB, IKBKE, IKBKG, IL12A, IL12B, IL1B, IL6, IL8, IRAK1, IRAK4, IRF3, IRF5, IRF7, JUN, LBP, LY96, MAP2K1, MAP2K2, MAP2K3, MAP2K4, MAP2K6, MAP2K7, MAP3K7, MAP3K7IP1, MAP3K7IP2, MAP3K8, MAPK1, MAPK10, MAPK11, MAPK12, MAPK13, MAPK14, MAPK3, MAPK8, MAPK9, MYD88, NFKB1, NFKB2, NFKBIA, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, RAC1, RELA, RIPK1, SPP1, STAT1, TBK1, TICAM1, TICAM2, TIRAP, TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9, TNF, TOLLIP, TRAF3, TRAF6 99 AKT1(12), AKT2(1), AKT3(3), CASP8(3), CD14(1), CD40(1), CD86(2), IFNA1(1), IFNA10(1), IFNA13(1), IFNA14(2), IFNA16(1), IFNA2(2), IFNA4(1), IFNA7(1), IFNAR1(1), IFNAR2(1), IFNB1(1), IKBKB(3), IKBKE(1), IL12A(1), IL12B(1), IL6(2), IRAK1(1), IRAK4(2), IRF3(2), JUN(1), LBP(1), MAP2K1(1), MAP2K2(1), MAP2K3(1), MAP2K4(20), MAP2K7(1), MAP3K7(1), MAP3K8(2), MAPK1(1), MAPK10(1), MAPK14(1), MAPK3(1), MAPK8(2), NFKB1(1), NFKB2(3), NFKBIA(1), PIK3CA(194), PIK3CB(4), PIK3CG(2), PIK3R1(14), PIK3R3(1), RELA(1), RIPK1(3), SPP1(2), STAT1(1), TBK1(1), TICAM1(2), TIRAP(2), TLR1(1), TLR2(1), TLR3(1), TLR4(8), TLR5(1), TLR7(5), TLR8(3), TLR9(1), TRAF3(1), TRAF6(2) 67859415 340 267 165 40 20 108 32 126 53 1 1.50e-13 <1.00e-15 <1.43e-14
4 ST_JNK_MAPK_PATHWAY JNKs are MAP kinases regulated by several levels of kinases (MAPKK, MAPKKK) and phosphorylate transcription factors and regulatory proteins. AKT1, ATF2, CDC42, DLD, DUSP10, DUSP4, DUSP8, GAB1, GADD45A, GCK, IL1R1, JUN, MAP2K4, MAP2K5, MAP2K7, MAP3K1, MAP3K10, MAP3K11, MAP3K12, MAP3K13, MAP3K2, MAP3K3, MAP3K4, MAP3K5, MAP3K7, MAP3K7IP1, MAP3K7IP2, MAP3K9, MAPK10, MAPK7, MAPK8, MAPK9, MYEF2, NFATC3, NR2C2, PAPPA, SHC1, TP53, TRAF6, ZAK 38 AKT1(12), ATF2(2), DLD(1), DUSP10(1), DUSP4(1), GAB1(1), GCK(2), IL1R1(1), JUN(1), MAP2K4(20), MAP2K5(2), MAP2K7(1), MAP3K1(46), MAP3K10(4), MAP3K11(1), MAP3K12(2), MAP3K13(5), MAP3K4(4), MAP3K5(2), MAP3K7(1), MAP3K9(3), MAPK10(1), MAPK8(2), MYEF2(2), NFATC3(3), NR2C2(1), PAPPA(4), SHC1(1), TP53(187), TRAF6(2), ZAK(1) 38087868 317 263 230 21 42 46 38 51 125 15 4.52e-13 <1.00e-15 <1.43e-14
5 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(12), AKT2(1), AKT3(3), BAD(1), CDK2(1), CDKN1B(5), CREB1(1), CREB3(1), EBP(1), ERBB4(6), F2RL2(1), GAB1(1), GRB2(1), GSK3A(1), IGF1(1), INPPL1(2), IRS1(1), IRS4(4), MET(5), MYC(1), NOLC1(2), PAK1(2), PAK2(1), PAK3(2), PAK6(1), PAK7(1), PARD3(3), PDK1(1), PIK3CA(194), PPP1R13B(2), PREX1(8), PTEN(17), PTK2(3), RPS6KA1(1), RPS6KA2(2), RPS6KA3(2), SHC1(1), SLC2A4(1), SOS1(4), SOS2(2), TSC1(3), TSC2(2), YWHAB(1) 57138393 306 247 132 28 18 98 38 117 34 1 2.78e-15 <1.00e-15 <1.43e-14
6 TCRPATHWAY T cell receptors bind to foreign peptides presented by MHC molecules and induce T cell activation. CALM1, CALM2, CALM3, CD3D, CD3E, CD3G, CD3Z, ELK1, FOS, FYN, GRB2, HRAS, JUN, LAT, LCK, MAP2K1, MAP2K4, MAP3K1, MAPK3, MAPK8, NFATC1, NFATC2, NFATC3, NFATC4, NFKB1, NFKBIA, PIK3CA, PIK3R1, PLCG1, PPP3CA, PPP3CB, PPP3CC, PRKCA, PRKCB1, PTPN7, RAC1, RAF1, RASA1, RELA, SHC1, SOS1, SYT1, TRA@, TRB@, VAV1, ZAP70 42 CD3E(1), CD3G(1), ELK1(2), GRB2(1), JUN(1), LAT(1), MAP2K1(1), MAP2K4(20), MAP3K1(46), MAPK3(1), MAPK8(2), NFATC1(1), NFATC2(1), NFATC3(3), NFATC4(3), NFKB1(1), NFKBIA(1), PIK3CA(194), PIK3R1(14), PLCG1(5), PPP3CA(3), PPP3CB(3), PTPN7(2), RAF1(1), RASA1(2), RELA(1), SHC1(1), SOS1(4), VAV1(2), ZAP70(1) 35946807 320 241 155 21 15 85 26 119 60 15 <1.00e-15 <1.00e-15 <1.43e-14
7 ST_B_CELL_ANTIGEN_RECEPTOR B cell receptors bind antigens and promote B cell activation. AKT1, AKT2, AKT3, BAD, BCR, BLNK, BTK, CD19, CSK, DAG1, EPHB2, GRB2, ITPKA, ITPKB, LYN, MAP2K1, MAP2K2, MAPK1, NFAT5, NFKB1, NFKB2, NFKBIA, NFKBIB, NFKBIE, NFKBIL1, NFKBIL2, PAG, PI3, PIK3CA, PIK3CD, PIK3R1, PLCG2, PPP1R13B, RAF1, SERPINA4, SHC1, SOS1, SOS2, SYK, VAV1 38 AKT1(12), AKT2(1), AKT3(3), BAD(1), BCR(1), BLNK(1), BTK(3), CD19(2), DAG1(1), EPHB2(2), GRB2(1), ITPKA(1), ITPKB(8), LYN(4), MAP2K1(1), MAP2K2(1), MAPK1(1), NFAT5(3), NFKB1(1), NFKB2(3), NFKBIA(1), NFKBIE(1), PI3(1), PIK3CA(194), PIK3R1(14), PLCG2(2), PPP1R13B(2), RAF1(1), SERPINA4(3), SHC1(1), SOS1(4), SOS2(2), SYK(2), VAV1(2) 39742716 281 240 108 15 18 96 25 115 26 1 <1.00e-15 <1.00e-15 <1.43e-14
8 HSA04150_MTOR_SIGNALING_PATHWAY Genes involved in mTOR signaling pathway AKT1, AKT2, AKT3, BRAF, CAB39, DDIT4, EIF4B, EIF4EBP1, FIGF, FRAP1, GBL, HIF1A, IGF1, INS, KIAA1303, LYK5, MAPK1, MAPK3, PDPK1, PGF, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PRKAA1, PRKAA2, RHEB, RICTOR, RPS6, RPS6KA1, RPS6KA2, RPS6KA3, RPS6KA6, RPS6KB1, RPS6KB2, STK11, TSC1, TSC2, ULK1, ULK2, ULK3, VEGFA, VEGFB, VEGFC 44 AKT1(12), AKT2(1), AKT3(3), BRAF(3), EIF4B(1), FIGF(2), HIF1A(1), IGF1(1), MAPK1(1), MAPK3(1), PIK3CA(194), PIK3CB(4), PIK3CG(2), PIK3R1(14), PIK3R3(1), PRKAA1(1), PRKAA2(3), RHEB(1), RICTOR(3), RPS6(2), RPS6KA1(1), RPS6KA2(2), RPS6KA3(2), RPS6KA6(3), RPS6KB2(4), TSC1(3), TSC2(2), ULK1(2), ULK2(1) 41043171 271 234 98 23 11 96 24 117 23 0 5.11e-15 <1.00e-15 <1.43e-14
9 NFATPATHWAY Cardiac hypertrophy is induced by NF-ATc4 and GATA4, which are stimulated through calcineurin activated by CaMK. ACTA1, AGT, AKT1, CALM1, CALM2, CALM3, CALR, CAMK1, CAMK1G, CAMK4, CREBBP, CSNK1A1, CTF1, DTR, EDN1, ELSPBP1, F2, FGF2, FKBP1A, GATA4, GSK3B, HAND1, HAND2, HRAS, IGF1, LIF, MAP2K1, MAPK1, MAPK14, MAPK3, MAPK8, MEF2C, MYH2, NFATC1, NFATC2, NFATC3, NFATC4, NKX2-5, NPPA, PIK3CA, PIK3R1, PPP3CA, PPP3CB, PPP3CC, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, RAF1, RPS6KB1, SYT1 52 ACTA1(1), AGT(3), AKT1(12), CALR(1), CAMK1(2), CAMK1G(1), CREBBP(2), EDN1(2), F2(3), HAND2(2), IGF1(1), LIF(3), MAP2K1(1), MAPK1(1), MAPK14(1), MAPK3(1), MAPK8(2), MEF2C(2), MYH2(2), NFATC1(1), NFATC2(1), NFATC3(3), NFATC4(3), NPPA(1), PIK3CA(194), PIK3R1(14), PPP3CA(3), PPP3CB(3), PRKAR1A(1), PRKAR2A(1), PRKAR2B(1), RAF1(1) 38119302 270 232 97 24 7 90 33 119 21 0 4.46e-14 <1.00e-15 <1.43e-14
10 ST_DIFFERENTIATION_PATHWAY_IN_PC12_CELLS Rat-derived PC12 cells respond to nerve growth factor (NGF) and PACAP to differentiate into neuronal cells. AKT1, ASAH1, ATF1, BRAF, CAMP, CREB1, CREB3, CREB5, CREBBP, CRKL, DAG1, EGR1, EGR2, EGR3, EGR4, ELK1, FRS2, GAS, GNAQ, GRF2, JUN, MAP1B, MAP2K4, MAP2K7, MAPK1, MAPK10, MAPK3, MAPK8, MAPK8IP1, MAPK8IP2, MAPK8IP3, MAPK9, NTRK1, OPN1LW, PACAP, PIK3C2G, PIK3CA, PIK3CD, PIK3R1, PTPN11, RPS6KA3, SH2B, SHC1, SRC, TERF2IP, TH, TUBA3 42 AKT1(12), ASAH1(1), BRAF(3), CREB1(1), CREB3(1), CREBBP(2), CRKL(1), DAG1(1), EGR1(1), EGR2(1), EGR3(3), ELK1(2), GNAQ(1), JUN(1), MAP1B(1), MAP2K4(20), MAP2K7(1), MAPK1(1), MAPK10(1), MAPK3(1), MAPK8(2), MAPK8IP1(1), MAPK8IP2(2), MAPK8IP3(4), NTRK1(3), OPN1LW(1), PIK3C2G(2), PIK3CA(194), PIK3R1(14), PTPN11(1), RPS6KA3(2), SHC1(1), TERF2IP(2) 39579462 285 232 111 18 15 90 25 116 39 0 <1.00e-15 <1.00e-15 <1.43e-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 EOSINOPHILSPATHWAY Recruitment of eosinophils in the inflammatory response observed in asthma occurs via the chemoattractant eotaxin binding to the CCR3 receptor. CCL11, CCL5, CCR3, CSF2, HLA-DRA, HLA-DRB1, IL3, IL5 7 CCL11(1), CCR3(1), HLA-DRB1(4) 1828749 6 6 6 1 0 1 1 2 2 0 0.43 0.017 1
2 STILBENE_COUMARINE_AND_LIGNIN_BIOSYNTHESIS EPX, GBA3, LPO, MPO, PRDX1, PRDX2, PRDX5, PRDX6, TPO, TYR 10 EPX(1), LPO(5), MPO(2), PRDX1(1), PRDX5(1), TPO(6), TYR(4) 7428057 20 20 20 2 6 2 5 3 4 0 0.067 0.019 1
3 ST_PAC1_RECEPTOR_PATHWAY The signaling peptide PACAP binds to its receptor, PAC1R, which activates adenylyl cyclase and phospholipase C. ASAH1, CAMP, DAG1, GAS, GNAQ, ITPKA, ITPKB, PACAP 6 ASAH1(1), DAG1(1), GNAQ(1), ITPKA(1), ITPKB(8) 4432701 12 12 12 0 2 1 3 4 2 0 0.04 0.023 1
4 HSA00601_GLYCOSPHINGOLIPID_BIOSYNTHESIS_LACTOSERIES Genes involved in glycosphingolipid biosynthesis - lactoseries ABO, B3GALT1, B3GALT2, B3GALT5, B3GNT5, FUT1, FUT2, FUT3, ST3GAL3, ST3GAL4 10 ABO(4), B3GALT1(1), B3GALT2(1), B3GALT5(1), FUT2(2), FUT3(4), ST3GAL3(1), ST3GAL4(1) 5407662 15 15 14 2 4 5 2 2 2 0 0.05 0.034 1
5 CREMPATHWAY The transcription factor CREM activates a post-meiotic transcriptional cascade culminating in spermatogenesis. ADCY1, CREM, FHL5, FSHB, FSHR, GNAS, XPO1 7 ADCY1(3), CREM(2), FHL5(1), FSHR(4), GNAS(5), XPO1(3) 6833346 18 18 18 2 4 4 3 5 2 0 0.13 0.043 1
6 BLOOD_GROUP_GLYCOLIPID_BIOSYNTHESIS_LACTOSERIES ABO, FUT1, FUT2, FUT3, FUT5, FUT6, SIAT6, ST3GAL3 7 ABO(4), FUT2(2), FUT3(4), FUT5(1), ST3GAL3(1) 3810105 12 12 11 2 4 3 1 2 2 0 0.096 0.065 1
7 HSA00940_PHENYLPROPANOID_BIOSYNTHESIS Genes involved in phenylpropanoid biosynthesis EPX, GBA, GBA3, LPO, MPO, PRDX6, TPO 7 EPX(1), LPO(5), MPO(2), TPO(6) 6402396 14 14 14 0 6 1 2 2 3 0 0.012 0.081 1
8 INOSITOL_METABOLISM ALDH6A1, ALDOA, ALDOB, ALDOC, TPI1 5 ALDOA(4), ALDOB(2), TPI1(2) 2928939 8 8 8 0 0 4 3 0 1 0 0.051 0.088 1
9 METHIONINEPATHWAY Catabolic Pathways for Methionine, Isoleucine, Threonine and Valine BCKDHB, BCKDK, CBS, CTH, MUT 5 BCKDK(2), CBS(2), CTH(3), MUT(1) 3739125 8 8 8 0 1 1 1 1 4 0 0.14 0.12 1
10 SA_DIACYLGLYCEROL_SIGNALING DAG (diacylglycerol) signaling activity ESR1, ESR2, ITPKA, PDE1A, PDE1B, PLCB1, PLCB2, PRL, TRH, VIP 10 ESR1(2), ESR2(2), ITPKA(1), PDE1A(2), PDE1B(2), PLCB1(4), PLCB2(2), VIP(1) 8374626 16 16 16 2 2 6 3 3 2 0 0.12 0.16 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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