Skin Cutaneous Melanoma: Mutation Analysis (MutSig v2.0)
(BRAF_Hotspot_Mutants cohort)
Maintained by Dan DiCara (Broad Institute)
Overview
Introduction

This report serves to describe the mutational landscape and properties of a given individual set, as well as rank genes and genesets according to mutational significance. MutSig v2.0 was used to generate the results found in this report.

  • Working with individual set: SKCM-BRAF_Hotspot_Mutants

  • Number of patients in set: 97

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:SKCM-BRAF_Hotspot_Mutants.final_analysis_set.maf

  • Significantly mutated genes (q ≤ 0.1): 58

  • Mutations seen in COSMIC: 232

  • Significantly mutated genes in COSMIC territory: 10

  • Genes with clustered mutations (≤ 3 aa apart): 899

  • Significantly mutated genesets: 2

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

Mutation Preprocessing

  • Read 97 MAFs of type "Broad"

  • Total number of mutations in input MAFs: 55227

  • After removing 2 mutations outside chr1-24: 55225

  • After removing 325 blacklisted mutations: 54900

  • After removing 1075 noncoding mutations: 53825

Mutation Filtering

  • Number of mutations before filtering: 53825

  • After removing 723 mutations outside gene set: 53102

  • After removing 32 mutations outside category set: 53070

Results
Breakdown of Mutations by Type

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

type count
Frame_Shift_Del 304
Frame_Shift_Ins 94
In_Frame_Del 105
In_Frame_Ins 13
Missense_Mutation 33009
Nonsense_Mutation 1986
Nonstop_Mutation 14
Silent 16955
Splice_Site 575
Translation_Start_Site 15
Total 53070
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
(C/T)p*C->T 23000 771897641 3e-05 30 2.3 1.6
(A/G)p*C->T 2721 647491941 4.2e-06 4.2 0.32 1.9
A->G 1765 1373132947 1.3e-06 1.3 0.099 2.3
transver 5538 2792522529 2e-06 2 0.15 5
indel+null 3060 2792522529 1.1e-06 1.1 0.085 NaN
double_null 31 2792522529 1.1e-08 0.011 0.00086 NaN
Total 36115 2792522529 0.000013 13 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: SKCM-BRAF_Hotspot_Mutants.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: (C/T)p*C->T

  • n2 = number of nonsilent mutations of type: (A/G)p*C->T

  • n3 = number of nonsilent mutations of type: A->G

  • n4 = number of nonsilent mutations of type: transver

  • n5 = number of nonsilent mutations of type: indel+null

  • n6 = number of nonsilent mutations of type: double_null

  • p_classic = p-value for the observed amount of nonsilent mutations being elevated in this gene

  • p_ns_s = p-value for the observed nonsilent/silent ratio being elevated in this gene

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

  • p_joint = p-value for clustering + conservation

  • p = p-value (overall)

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

Table 3.  Get Full Table A Ranked List of Significantly Mutated Genes. Number of significant genes found: 58. 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 BRAF v-raf murine sarcoma viral oncogene homolog B1 215475 99 97 4 1 2 0 0 97 0 0 <1.00e-15 1.5e-07 0 0 <1.00e-15 <1.80e-11
2 CDKN2A cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4) 89548 12 12 10 0 4 0 0 0 8 0 3.83e-10 0.053 0.000035 0.000037 4.62e-13 4.17e-09
3 PTEN phosphatase and tensin homolog (mutated in multiple advanced cancers 1) 108063 12 12 11 0 1 0 3 1 7 0 4.08e-13 0.089 0.74 0.26 3.24e-12 1.95e-08
4 OR4K1 olfactory receptor, family 4, subfamily K, member 1 91018 16 14 13 2 14 1 0 0 1 0 3.30e-10 0.0064 0.78 0.89 6.76e-09 2.74e-05
5 RPTN repetin 229211 22 18 21 1 13 1 4 4 0 0 6.78e-10 0.011 0.73 0.49 7.60e-09 2.74e-05
6 TP53 tumor protein p53 118128 11 10 11 1 2 0 2 2 5 0 3.05e-08 0.094 0.064 0.019 1.27e-08 3.82e-05
7 ACSM2B acyl-CoA synthetase medium-chain family member 2B 168684 20 16 17 2 16 0 0 2 2 0 1.16e-08 0.0046 0.94 1 2.24e-07 0.000577
8 C7orf58 chromosome 7 open reading frame 58 301090 16 13 15 1 10 1 1 0 4 0 7.99e-06 0.011 0.001 0.0036 5.22e-07 0.00118
9 GFRAL GDNF family receptor alpha like 116103 12 11 12 2 7 1 0 2 2 0 5.58e-08 0.18 0.39 0.58 5.93e-07 0.00119
10 LILRA1 leukocyte immunoglobulin-like receptor, subfamily A (with TM domain), member 1 145978 12 12 12 1 7 1 2 2 0 0 1.35e-07 0.024 0.39 0.33 7.98e-07 0.00144
11 CDK4 cyclin-dependent kinase 4 91043 4 4 3 0 0 0 0 4 0 0 0.00337 0.42 0.032 0.000019 1.12e-06 0.00184
12 DSG3 desmoglein 3 (pemphigus vulgaris antigen) 295650 20 17 18 1 18 2 0 0 0 0 4.20e-07 0.0042 0.69 0.4 2.77e-06 0.00416
13 PRAMEF11 PRAME family member 11 120600 11 9 8 3 3 0 3 4 1 0 1.89e-06 0.29 0.89 0.11 3.31e-06 0.00441
14 RFX6 regulatory factor X, 6 255411 14 12 14 1 11 0 1 1 1 0 2.06e-06 0.038 0.11 0.1 3.42e-06 0.00441
15 SLC4A10 solute carrier family 4, sodium bicarbonate transporter-like, member 10 266470 15 14 15 1 10 0 0 1 4 0 7.19e-07 0.029 0.93 1 1.09e-05 0.0131
16 SERPINB4 serpin peptidase inhibitor, clade B (ovalbumin), member 4 110945 13 10 13 2 10 0 0 1 2 0 1.28e-06 0.036 0.81 0.65 1.25e-05 0.0141
17 NBPF1 neuroblastoma breakpoint family, member 1 313745 18 14 16 1 9 1 1 6 1 0 1.56e-05 0.011 0.1 0.077 1.75e-05 0.0186
18 IL32 interleukin 32 48362 4 4 2 1 0 0 0 1 3 0 0.000187 0.93 0.86 0.011 2.90e-05 0.0290
19 OR4C15 olfactory receptor, family 4, subfamily C, member 15 107246 10 10 8 2 10 0 0 0 0 0 3.61e-06 0.055 0.75 0.64 3.20e-05 0.0296
20 NELL1 NEL-like 1 (chicken) 232214 11 11 11 1 4 2 0 2 3 0 2.35e-06 0.1 0.92 1 3.28e-05 0.0296
21 CDR1 cerebellar degeneration-related protein 1, 34kDa 76856 7 7 7 1 4 0 0 0 3 0 8.33e-06 0.26 0.68 0.35 4.03e-05 0.0346
22 GK2 glycerol kinase 2 160995 14 12 13 1 11 0 0 2 1 0 3.26e-06 0.057 0.58 1 4.44e-05 0.0365
23 OR5D13 olfactory receptor, family 5, subfamily D, member 13 90951 9 7 8 1 6 1 0 0 2 0 1.51e-05 0.034 0.91 0.26 5.27e-05 0.0412
24 ZNF215 zinc finger protein 215 152546 8 8 8 1 2 0 3 2 1 0 6.81e-06 0.2 0.8 0.6 5.49e-05 0.0412
25 TRHR thyrotropin-releasing hormone receptor 115831 8 8 7 1 5 3 0 0 0 0 4.37e-05 0.045 0.32 0.13 7.30e-05 0.0488
26 MORF4 mortality factor 4 68955 8 8 8 1 6 0 0 1 1 0 5.65e-06 0.14 0.92 1 7.39e-05 0.0488
27 PRSS1 protease, serine, 1 (trypsin 1) 74104 8 8 8 2 6 0 1 1 0 0 9.68e-06 0.18 0.64 0.6 7.55e-05 0.0488
28 UNC119B unc-119 homolog B (C. elegans) 68908 4 4 4 1 1 0 0 3 0 0 0.00385 0.6 0.0017 0.0015 7.57e-05 0.0488
29 RGS21 regulator of G-protein signaling 21 43410 5 5 5 0 3 0 0 2 0 0 7.85e-05 0.21 0.63 0.077 7.85e-05 0.0489
30 FUT9 fucosyltransferase 9 (alpha (1,3) fucosyltransferase) 99525 7 7 7 1 4 1 1 1 0 0 5.09e-05 0.22 0.089 0.13 8.54e-05 0.0514
31 CCDC102B coiled-coil domain containing 102B 148571 9 9 7 1 7 1 0 0 1 0 8.62e-05 0.11 0.6 0.086 9.53e-05 0.0543
32 ST6GAL2 ST6 beta-galactosamide alpha-2,6-sialyltranferase 2 138224 14 13 13 3 11 1 0 1 1 0 2.22e-05 0.068 0.087 0.34 9.62e-05 0.0543
33 OR11L1 olfactory receptor, family 11, subfamily L, member 1 93528 8 8 6 0 7 0 0 1 0 0 9.29e-05 0.0035 0.71 0.085 0.000101 0.0550
34 GIMAP4 GTPase, IMAP family member 4 96124 4 4 3 1 3 0 0 1 0 0 0.0170 0.41 0.18 0.00052 0.000112 0.0592
35 ICA1L islet cell autoantigen 1,69kDa-like 146534 5 5 3 0 1 0 0 3 1 0 0.0120 0.46 0.0006 0.00076 0.000115 0.0592
BRAF

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

CDKN2A

Figure S2.  This figure depicts the distribution of mutations and mutation types across the CDKN2A significant gene.

PTEN

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

OR4K1

Figure S4.  This figure depicts the distribution of mutations and mutation types across the OR4K1 significant gene.

RPTN

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

TP53

Figure S6.  This figure depicts the distribution of mutations and mutation types across the TP53 significant gene.

ACSM2B

Figure S7.  This figure depicts the distribution of mutations and mutation types across the ACSM2B significant gene.

C7orf58

Figure S8.  This figure depicts the distribution of mutations and mutation types across the C7orf58 significant gene.

GFRAL

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

LILRA1

Figure S10.  This figure depicts the distribution of mutations and mutation types across the LILRA1 significant gene.

CDK4

Figure S11.  This figure depicts the distribution of mutations and mutation types across the CDK4 significant gene.

DSG3

Figure S12.  This figure depicts the distribution of mutations and mutation types across the DSG3 significant gene.

PRAMEF11

Figure S13.  This figure depicts the distribution of mutations and mutation types across the PRAMEF11 significant gene.

RFX6

Figure S14.  This figure depicts the distribution of mutations and mutation types across the RFX6 significant gene.

SLC4A10

Figure S15.  This figure depicts the distribution of mutations and mutation types across the SLC4A10 significant gene.

SERPINB4

Figure S16.  This figure depicts the distribution of mutations and mutation types across the SERPINB4 significant gene.

NBPF1

Figure S17.  This figure depicts the distribution of mutations and mutation types across the NBPF1 significant gene.

IL32

Figure S18.  This figure depicts the distribution of mutations and mutation types across the IL32 significant gene.

OR4C15

Figure S19.  This figure depicts the distribution of mutations and mutation types across the OR4C15 significant gene.

NELL1

Figure S20.  This figure depicts the distribution of mutations and mutation types across the NELL1 significant gene.

CDR1

Figure S21.  This figure depicts the distribution of mutations and mutation types across the CDR1 significant gene.

GK2

Figure S22.  This figure depicts the distribution of mutations and mutation types across the GK2 significant gene.

OR5D13

Figure S23.  This figure depicts the distribution of mutations and mutation types across the OR5D13 significant gene.

ZNF215

Figure S24.  This figure depicts the distribution of mutations and mutation types across the ZNF215 significant gene.

TRHR

Figure S25.  This figure depicts the distribution of mutations and mutation types across the TRHR significant gene.

PRSS1

Figure S26.  This figure depicts the distribution of mutations and mutation types across the PRSS1 significant gene.

UNC119B

Figure S27.  This figure depicts the distribution of mutations and mutation types across the UNC119B significant gene.

RGS21

Figure S28.  This figure depicts the distribution of mutations and mutation types across the RGS21 significant gene.

FUT9

Figure S29.  This figure depicts the distribution of mutations and mutation types across the FUT9 significant gene.

CCDC102B

Figure S30.  This figure depicts the distribution of mutations and mutation types across the CCDC102B significant gene.

ST6GAL2

Figure S31.  This figure depicts the distribution of mutations and mutation types across the ST6GAL2 significant gene.

OR11L1

Figure S32.  This figure depicts the distribution of mutations and mutation types across the OR11L1 significant gene.

GIMAP4

Figure S33.  This figure depicts the distribution of mutations and mutation types across the GIMAP4 significant gene.

COSMIC analyses

In this analysis, COSMIC is used as a filter to increase power by restricting the territory of each gene. Cosmic version: v48.

Table 4.  Get Full Table Significantly mutated genes (COSMIC territory only). To access the database please go to: COSMIC. Number of significant genes found: 10. Number of genes displayed: 10

rank gene description n cos n_cos N_cos cos_ev p q
1 BRAF v-raf murine sarcoma viral oncogene homolog B1 99 89 97 8633 1393888 0 0
2 CDKN2A cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4) 12 332 12 32204 330 0 0
3 TP53 tumor protein p53 11 356 11 34532 638 1.9e-12 2.9e-09
4 PTEN phosphatase and tensin homolog (mutated in multiple advanced cancers 1) 12 767 12 74399 308 5.4e-10 6.1e-07
5 NAP1L2 nucleosome assembly protein 1-like 2 6 1 2 97 2 7.8e-07 0.0007
6 CAMTA1 calmodulin binding transcription activator 1 8 2 2 194 2 3.1e-06 0.0018
7 CCNA1 cyclin A1 8 2 2 194 4 3.1e-06 0.0018
8 STK19 serine/threonine kinase 19 2 2 2 194 4 3.1e-06 0.0018
9 IDH1 isocitrate dehydrogenase 1 (NADP+), soluble 3 5 2 485 2984 2e-05 0.0098
10 DCLK3 doublecortin-like kinase 3 5 6 2 582 2 0.000028 0.013

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
1006 BRAF v-raf murine sarcoma viral oncogene homolog B1 99 0 3403 3403 3403 3403 3403 3403
10684 TTN titin 291 0 11 14 30 11 14 30
6304 MUC16 mucin 16, cell surface associated 227 0 9 25 66 9 25 66
2879 DNAH5 dynein, axonemal, heavy chain 5 103 0 8 13 35 8 13 35
7436 PCLO piccolo (presynaptic cytomatrix protein) 75 0 6 14 20 6 14 20
7988 PRAMEF11 PRAME family member 11 11 0 6 10 10 6 10 10
2264 CNTN5 contactin 5 24 0 6 9 12 6 9 12
729 ASXL3 additional sex combs like 3 (Drosophila) 28 0 6 7 11 6 7 11
8529 RGS7 regulator of G-protein signaling 7 13 0 6 7 7 6 7 7
2295 COL21A1 collagen, type XXI, alpha 1 13 0 6 6 17 6 6 17

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: 2. 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 ST_G_ALPHA_S_PATHWAY The G-alpha-s protein activates adenylyl cyclases, which catalyze cAMP formation. ASAH1, BF, BFAR, BRAF, CAMP, CREB1, CREB3, CREB5, EPAC, GAS, GRF2, MAPK1, RAF1, SNX13, SRC, TERF2IP 12 BRAF(99), CREB5(2), MAPK1(1), RAF1(3), SNX13(1) 1602469 106 97 11 7 6 0 1 98 1 0 0.00014 1.9e-15 1.2e-12
2 ST_ERK1_ERK2_MAPK_PATHWAY The Erk1 and Erk2 MAP kinase pathways are regulated by Raf, Mos, and Tpl-2. ARAF1, ATF1, BAD, BRAF, COPEB, CREB1, CREB3, CREB5, DUSP4, DUSP6, DUSP9, EEF2K, EIF4E, GRB2, HTATIP, MAP2K1, MAP2K2, MAP3K8, MAPK1, MAPK3, MKNK1, MKNK2, MOS, NFKB1, RAP1A, RPS6KA1, RPS6KA2, RPS6KA3, SHC1, SOS1, SOS2, TRAF3 29 ATF1(3), BRAF(99), CREB5(2), DUSP6(1), GRB2(1), MAP2K1(3), MAP2K2(2), MAPK1(1), MKNK1(2), MOS(1), NFKB1(1), RPS6KA1(1), RPS6KA2(5), RPS6KA3(1), SOS1(3), SOS2(4), TRAF3(2) 4188759 132 97 35 21 22 1 2 104 3 0 0.0072 3.7e-14 1.1e-11
3 SA_G1_AND_S_PHASES Cdk2, 4, and 6 bind cyclin D in G1, while cdk2/cyclin E promotes the G1/S transition. ARF1, ARF3, CCND1, CDK2, CDK4, CDKN1A, CDKN1B, CDKN2A, CFL1, E2F1, E2F2, MDM2, NXT1, PRB1, TP53 15 CDK4(4), CDKN1A(1), CDKN2A(12), CFL1(1), E2F2(1), MDM2(2), PRB1(7), TP53(11) 1208404 39 27 35 5 13 1 2 10 13 0 0.0074 0.0013 0.27
4 SA_REG_CASCADE_OF_CYCLIN_EXPR Expression of cyclins regulates progression through the cell cycle by activating cyclin-dependent kinases. CCNA1, CCNA2, CCND1, CCNE1, CCNE2, CDK2, CDK4, CDKN1B, CDKN2A, E2F1, E2F2, E2F4, PRB1 13 CCNA1(8), CCNE1(1), CCNE2(5), CDK4(4), CDKN2A(12), E2F2(1), PRB1(7) 1286870 38 28 34 5 19 0 1 10 8 0 0.0088 0.0028 0.43
5 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(3), AKT2(2), AKT3(1), BRAF(99), FIGF(2), HIF1A(3), IGF1(5), MAPK1(1), PDPK1(1), PIK3CA(3), PIK3CB(9), PIK3CD(3), PIK3CG(8), PIK3R1(3), PIK3R2(3), PIK3R5(7), PRKAA2(6), RICTOR(2), RPS6KA1(1), RPS6KA2(5), RPS6KA3(1), RPS6KA6(7), STK11(2), TSC1(1), TSC2(3), ULK1(1), ULK2(3), ULK3(1), VEGFA(2), VEGFB(1), VEGFC(6) 7494768 195 97 99 34 51 3 4 125 11 1 0.000081 0.021 1
6 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(3), ATF1(3), BRAF(99), CREB5(2), CREBBP(4), CRKL(1), DAG1(1), EGR2(2), EGR4(1), ELK1(1), FRS2(1), GNAQ(1), JUN(1), MAP1B(5), MAP2K4(1), MAP2K7(1), MAPK1(1), MAPK10(2), MAPK8IP1(1), MAPK8IP2(1), MAPK9(1), NTRK1(5), OPN1LW(1), PIK3C2G(10), PIK3CA(3), PIK3CD(3), PIK3R1(3), PTPN11(2), RPS6KA3(1), TH(4) 7267574 165 97 70 30 40 5 2 113 4 1 0.00077 0.021 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 10 CCL11(1), CCR3(5), CD4(5), HLA-DRA(3), HLA-DRB1(1), IL1B(2), IL5(1), IL5RA(3) 761782 21 19 20 4 15 1 0 4 1 0 0.01 0.03 1
8 STEROID_BIOSYNTHESIS CYP17A1, F13B, HSD17B1, HSD17B2, HSD17B3, HSD17B4, HSD17B7, HSD3B1, HSD3B2 9 CYP17A1(2), F13B(7), HSD17B2(3), HSD17B4(4), HSD3B1(3), HSD3B2(3) 1145924 22 20 21 3 16 0 2 2 1 1 0.007 0.034 1
9 SLRPPATHWAY Small leucine-rich proteoglycans (SLRPs) interact with and reorganize collagen fibers in the extracellular matrix. BGN, DCN, DSPG3, FMOD, KERA, LUM 5 BGN(3), DCN(7), KERA(2), LUM(4) 506483 16 13 16 4 11 2 0 0 3 0 0.032 0.06 1
10 BBCELLPATHWAY Fas ligand expression by T cells induces apoptosis in Fas-expressing, inactive B cells. CD28, CD4, HLA-DRA, HLA-DRB1, TNFRSF5, TNFRSF6, TNFSF5, TNFSF6 4 CD4(5), HLA-DRA(3), HLA-DRB1(1) 334543 9 8 9 0 5 1 0 3 0 0 0.019 0.077 1

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

rank geneset description genes N_genes mut_tally N n npat nsite nsil n1 n2 n3 n4 n5 n6 p_ns_s p q
1 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 10 CCL11(1), CCR3(5), CD4(5), HLA-DRA(3), HLA-DRB1(1), IL1B(2), IL5(1), IL5RA(3) 761782 21 19 20 4 15 1 0 4 1 0 0.01 0.03 1
2 STEROID_BIOSYNTHESIS CYP17A1, F13B, HSD17B1, HSD17B2, HSD17B3, HSD17B4, HSD17B7, HSD3B1, HSD3B2 9 CYP17A1(2), F13B(7), HSD17B2(3), HSD17B4(4), HSD3B1(3), HSD3B2(3) 1145924 22 20 21 3 16 0 2 2 1 1 0.007 0.034 1
3 SLRPPATHWAY Small leucine-rich proteoglycans (SLRPs) interact with and reorganize collagen fibers in the extracellular matrix. BGN, DCN, DSPG3, FMOD, KERA, LUM 5 BGN(3), DCN(7), KERA(2), LUM(4) 506483 16 13 16 4 11 2 0 0 3 0 0.032 0.06 1
4 BBCELLPATHWAY Fas ligand expression by T cells induces apoptosis in Fas-expressing, inactive B cells. CD28, CD4, HLA-DRA, HLA-DRB1, TNFRSF5, TNFRSF6, TNFSF5, TNFSF6 4 CD4(5), HLA-DRA(3), HLA-DRB1(1) 334543 9 8 9 0 5 1 0 3 0 0 0.019 0.077 1
5 FOSBPATHWAY FOSB gene expression and drug abuse CDK5, FOSB, GRIA2, JUND, PPP1R1B 5 CDK5(1), FOSB(2), GRIA2(14) 526332 17 13 17 4 12 2 1 1 1 0 0.087 0.079 1
6 HSA00950_ALKALOID_BIOSYNTHESIS_I Genes involved in alkaloid biosynthesis I DDC, GOT1, GOT2, TAT, TYR 5 DDC(4), GOT1(3), GOT2(1), TAT(4), TYR(4) 673736 16 13 16 3 10 2 1 1 2 0 0.059 0.11 1
7 ASBCELLPATHWAY B cells require interaction with helper T cells to produce antigen-specific immunoglobulins as a key element of the human immune response. CD28, CD4, CD80, HLA-DRA, HLA-DRB1, IL10, IL2, IL4, TNFRSF5, TNFRSF6, TNFSF5, TNFSF6 8 CD4(5), CD80(3), HLA-DRA(3), HLA-DRB1(1), IL10(1) 562026 13 9 13 1 5 1 1 6 0 0 0.036 0.13 1
8 PLCPATHWAY Phospholipase C hydrolyzes the membrane lipid PIP2 to DAG, which activates protein kinase C, and IP3, which causes calcium influx. AKT1, PIK3CA, PIK3R1, PLCB1, PLCG1, PRKCA, PRKCB1, VAV1 7 AKT1(3), PIK3CA(3), PIK3R1(3), PLCB1(16), PLCG1(6), PRKCA(2), VAV1(5) 1832035 38 28 38 6 24 1 2 6 4 1 0.0026 0.14 1
9 HSA00472_D_ARGININE_AND_D_ORNITHINE_METABOLISM Genes involved in D-arginine and D-ornithine metabolism DAO 1 DAO(3) 102790 3 3 3 1 2 0 1 0 0 0 0.54 0.16 1
10 HSA00550_PEPTIDOGLYCAN_BIOSYNTHESIS Genes involved in peptidoglycan biosynthesis GLUL, PGLYRP2 2 GLUL(2), PGLYRP2(8) 260514 10 6 10 2 6 1 1 2 0 0 0.16 0.18 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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