Skin Cutaneous Melanoma: Mutation Analysis (MutSig v1.5)
(All_Primary 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 v1.5 was used to generate the results found in this report.

  • Working with individual set: SKCM-All_Primary

  • Number of patients in set: 38

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-All_Primary.final_analysis_set.maf

  • Significantly mutated genes (q ≤ 0.1): 19

  • Mutations seen in COSMIC: 81

  • Significantly mutated genes in COSMIC territory: 5

  • Genes with clustered mutations (≤ 3 aa apart): 148

  • Significantly mutated genesets: 4

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

Mutation Preprocessing

  • Read 38 MAFs of type "Broad"

  • Total number of mutations in input MAFs: 18327

  • After removing 1 mutations outside chr1-24: 18326

  • After removing 135 blacklisted mutations: 18191

  • After removing 368 noncoding mutations: 17823

Mutation Filtering

  • Number of mutations before filtering: 17823

  • After removing 240 mutations outside gene set: 17583

  • After removing 3 mutations outside category set: 17580

Results
Breakdown of Mutations by Type

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

type count
Frame_Shift_Del 101
Frame_Shift_Ins 36
In_Frame_Del 32
In_Frame_Ins 8
Missense_Mutation 10885
Nonsense_Mutation 682
Nonstop_Mutation 3
Silent 5642
Splice_Site 180
Translation_Start_Site 11
Total 17580
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 8028 304598383 0.000026 26 2.4 1.6
(A/G)p*C->T 970 255685633 3.8e-06 3.8 0.35 1.9
A->G 505 540676925 9.3e-07 0.93 0.086 2.3
transver 1391 1100960941 1.3e-06 1.3 0.12 5
indel+null 1041 1100960941 9.5e-07 0.95 0.087 NaN
double_null 3 1100960941 2.7e-09 0.0027 0.00025 NaN
Total 11938 1100960941 0.000011 11 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-All_Primary.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_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)

Table 3.  Get Full Table A Ranked List of Significantly Mutated Genes. Number of significant genes found: 19. 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_ns_s p q
1 BRAF v-raf murine sarcoma viral oncogene homolog B1 84542 24 23 4 0 1 0 1 22 0 0 0.0077 1.1e-15 2e-11
2 NRAS neuroblastoma RAS viral (v-ras) oncogene homolog 22263 6 6 1 0 0 0 5 1 0 0 0.12 9.9e-12 8.9e-08
3 FAM135B family with sequence similarity 135, member B 163134 13 13 12 1 9 0 0 3 1 0 0.029 1e-08 0.000062
4 PRB2 proline-rich protein BstNI subfamily 2 47532 9 8 7 0 7 0 0 2 0 0 0.25 3.9e-08 0.00018
5 TLL1 tolloid-like 1 115472 10 9 10 1 6 1 0 0 3 0 0.19 4.6e-07 0.0017
6 PTEN phosphatase and tensin homolog (mutated in multiple advanced cancers 1) 43686 5 5 5 0 1 0 1 0 3 0 0.32 8.5e-07 0.0026
7 PPP6C protein phosphatase 6, catalytic subunit 38199 5 5 4 0 4 0 0 0 1 0 0.18 0.000017 0.04
8 ARID2 AT rich interactive domain 2 (ARID, RFX-like) 208651 9 8 9 1 2 0 0 0 7 0 0.32 0.000018 0.04
9 ADCYAP1R1 adenylate cyclase activating polypeptide 1 (pituitary) receptor type I 54688 5 5 5 1 2 1 1 0 1 0 0.24 0.000026 0.046
10 GLYAT glycine-N-acyltransferase 33932 4 4 4 0 2 0 0 0 2 0 0.23 0.000029 0.046
11 CLVS1 clavesin 1 41091 6 6 5 0 6 0 0 0 0 0 0.052 0.000029 0.046
12 CFHR1 complement factor H-related 1 32025 6 5 6 0 5 1 0 0 0 0 0.26 0.000031 0.046
13 ZFHX4 zinc finger homeobox 4 354049 12 11 12 1 6 2 1 3 0 0 0.065 0.000044 0.062
14 KCNC2 potassium voltage-gated channel, Shaw-related subfamily, member 2 62606 5 5 5 0 2 1 0 1 1 0 0.11 0.000051 0.063
15 FAM5C family with sequence similarity 5, member C 87218 8 7 8 2 5 0 0 3 0 0 0.39 0.000052 0.063
16 GRM8 glutamate receptor, metabotropic 8 105539 7 6 7 0 3 1 2 0 1 0 0.047 0.000058 0.064
17 OR5T3 olfactory receptor, family 5, subfamily T, member 3 38603 4 4 4 1 2 1 0 1 0 0 0.39 0.000062 0.064
18 PPP1R3A protein phosphatase 1, regulatory (inhibitor) subunit 3A 125297 7 7 7 1 5 0 1 1 0 0 0.4 0.000064 0.064
19 SCAND3 SCAN domain containing 3 146281 10 7 10 0 6 1 2 1 0 0 0.031 0.000067 0.064
20 KRTAP4-7 keratin associated protein 4-7 13851 2 2 1 1 0 0 2 0 0 0 0.88 0.00012 0.1
21 OR10A7 olfactory receptor, family 10, subfamily A, member 7 34863 3 3 3 0 0 2 0 0 1 0 0.53 0.00012 0.1
22 OR8I2 olfactory receptor, family 8, subfamily I, member 2 34565 4 4 4 1 3 0 1 0 0 0 0.25 0.00013 0.11
23 CAPN13 calpain 13 62498 6 6 6 1 5 0 1 0 0 0 0.18 0.00014 0.11
24 TP53 tumor protein p53 46527 4 4 4 0 1 1 0 0 2 0 0.17 0.00015 0.11
25 OR52E4 olfactory receptor, family 52, subfamily E, member 4 35508 4 4 4 0 2 0 0 2 0 0 0.19 0.00016 0.11
26 TNFSF14 tumor necrosis factor (ligand) superfamily, member 14 26552 4 4 4 0 3 0 0 0 1 0 0.097 0.00017 0.12
27 GRIA1 glutamate receptor, ionotropic, AMPA 1 108856 7 7 7 2 3 0 0 2 2 0 0.28 0.00018 0.12
28 C7 complement component 7 83984 9 7 9 0 8 0 0 0 1 0 0.054 0.00019 0.12
29 KCNE1 potassium voltage-gated channel, Isk-related family, member 1 14972 3 3 3 0 2 1 0 0 0 0 0.12 0.0002 0.13
30 LELP1 late cornified envelope-like proline-rich 1 11263 3 3 2 0 2 0 0 1 0 0 0.47 0.00022 0.14
31 IL7R interleukin 7 receptor 53335 6 5 6 1 3 0 0 2 1 0 0.29 0.00024 0.14
32 GIMAP5 GTPase, IMAP family member 5 35413 5 4 5 1 3 1 0 1 0 0 0.21 0.00024 0.14
33 NPHP1 nephronophthisis 1 (juvenile) 85394 4 4 3 0 0 2 0 0 2 0 0.28 0.00026 0.14
34 OR8D1 olfactory receptor, family 8, subfamily D, member 1 31504 4 4 4 0 3 0 0 1 0 0 0.085 0.00028 0.15
35 OR52M1 olfactory receptor, family 52, subfamily M, member 1 36275 4 4 4 0 3 0 0 1 0 0 0.1 0.00032 0.15
BRAF

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

NRAS

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

FAM135B

Figure S3.  This figure depicts the distribution of mutations and mutation types across the FAM135B significant gene.

TLL1

Figure S4.  This figure depicts the distribution of mutations and mutation types across the TLL1 significant gene.

PTEN

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

PPP6C

Figure S6.  This figure depicts the distribution of mutations and mutation types across the PPP6C significant gene.

ARID2

Figure S7.  This figure depicts the distribution of mutations and mutation types across the ARID2 significant gene.

ADCYAP1R1

Figure S8.  This figure depicts the distribution of mutations and mutation types across the ADCYAP1R1 significant gene.

GLYAT

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

CLVS1

Figure S10.  This figure depicts the distribution of mutations and mutation types across the CLVS1 significant gene.

CFHR1

Figure S11.  This figure depicts the distribution of mutations and mutation types across the CFHR1 significant gene.

ZFHX4

Figure S12.  This figure depicts the distribution of mutations and mutation types across the ZFHX4 significant gene.

KCNC2

Figure S13.  This figure depicts the distribution of mutations and mutation types across the KCNC2 significant gene.

FAM5C

Figure S14.  This figure depicts the distribution of mutations and mutation types across the FAM5C significant gene.

GRM8

Figure S15.  This figure depicts the distribution of mutations and mutation types across the GRM8 significant gene.

OR5T3

Figure S16.  This figure depicts the distribution of mutations and mutation types across the OR5T3 significant gene.

PPP1R3A

Figure S17.  This figure depicts the distribution of mutations and mutation types across the PPP1R3A significant gene.

SCAND3

Figure S18.  This figure depicts the distribution of mutations and mutation types across the SCAND3 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: 5. 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 24 89 23 3382 330218 0 0
2 NRAS neuroblastoma RAS viral (v-ras) oncogene homolog 6 33 6 1254 7788 0 0
3 IDH1 isocitrate dehydrogenase 1 (NADP+), soluble 3 5 2 190 2984 2.1e-06 0.0032
4 TP53 tumor protein p53 4 356 4 13528 1243 0.000017 0.018
5 PTEN phosphatase and tensin homolog (mutated in multiple advanced cancers 1) 5 767 5 29146 211 2e-05 0.018
6 CBL Cas-Br-M (murine) ecotropic retroviral transforming sequence 3 45 2 1710 7 0.00017 0.13
7 ADAM2 ADAM metallopeptidase domain 2 (fertilin beta) 3 1 1 38 1 0.00041 0.16
8 F13A1 coagulation factor XIII, A1 polypeptide 2 1 1 38 1 0.00041 0.16
9 GLRA2 glycine receptor, alpha 2 1 1 1 38 1 0.00041 0.16
10 NAP1L2 nucleosome assembly protein 1-like 2 3 1 1 38 1 0.00041 0.16

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
580 BRAF v-raf murine sarcoma viral oncogene homolog B1 24 0 91 105 105 91 105 105
3776 NRAS neuroblastoma RAS viral (v-ras) oncogene homolog 6 0 15 15 15 15 15 15
1192 CLIP1 CAP-GLY domain containing linker protein 1 5 0 3 3 3 3 3 3
3263 MAP2K1 mitogen-activated protein kinase kinase 1 3 0 3 3 3 3 3 3
4491 PRB2 proline-rich protein BstNI subfamily 2 9 0 2 2 3 2 2 3
717 C1orf173 chromosome 1 open reading frame 173 10 0 2 2 2 2 2 2
6265 ZNF208 zinc finger protein 208 8 0 2 2 2 2 2 2
3517 MUC16 mucin 16, cell surface associated 78 0 1 4 5 1 4 5
2041 FLG2 filaggrin family member 2 15 0 1 2 3 1 2 3
3438 MORC1 MORC family CW-type zinc finger 1 5 0 1 2 2 1 2 2

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: 4. 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 BFAR(1), BRAF(24), CREB5(2), TERF2IP(1) 628058 28 25 8 1 3 0 1 24 0 0 0.014 5.1e-15 3.2e-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(1), BRAF(24), CREB5(2), DUSP4(2), EEF2K(2), EIF4E(1), MAP2K1(3), MAP2K2(1), RPS6KA1(3), RPS6KA2(1), SHC1(2), SOS1(1), SOS2(2) 1650651 45 28 23 2 15 3 3 24 0 0 0.00011 6.5e-12 2e-09
3 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 ATF1(1), BRAF(24), CREB5(2), CREBBP(3), DAG1(1), FRS2(1), GNAQ(2), MAPK10(1), MAPK8(1), MAPK8IP1(1), MAPK8IP2(2), MAPK8IP3(1), MAPK9(2), NTRK1(4), OPN1LW(1), PIK3C2G(7), PIK3CA(1), PIK3R1(4), PTPN11(1), SHC1(2), TERF2IP(1) 2864884 63 30 43 5 20 3 4 31 5 0 0.000034 5.1e-09 1e-06
4 ST_ADRENERGIC Adrenergic receptors respond to epinephrine and norepinephrine signaling. AKT1, APC, AR, ASAH1, BF, BRAF, CAMP, CCL13, CCL15, CCL16, DAG1, EGFR, GAS, GNA11, GNA15, GNAI1, GNAQ, ITPKA, ITPKB, ITPR1, ITPR2, ITPR3, KCNJ3, KCNJ5, KCNJ9, MAPK1, MAPK10, MAPK14, PHKA2, PIK3CA, PIK3CD, PIK3R1, PITX2, PTX1, PTX3, RAF1, SRC 34 APC(3), BRAF(24), CCL13(1), DAG1(1), EGFR(1), GNAQ(2), ITPKA(1), ITPR1(7), ITPR2(1), ITPR3(3), KCNJ3(4), KCNJ5(3), MAPK10(1), PIK3CA(1), PIK3R1(4) 2987528 57 29 37 9 17 2 4 31 3 0 0.0045 0.00037 0.057
5 MAPKPATHWAY The mitogen-activated protein (MAP) kinase pathway is a common signaling mechanism and has four main sub-pathways: Erk, JNK/SAPK, p53, and ERK5. ARAF1, ATF2, BRAF, CEBPA, CHUK, CREB1, DAXX, ELK1, FOS, GRB2, HRAS, IKBKB, JUN, MAP2K1, MAP2K2, MAP2K3, MAP2K4, MAP2K5, MAP2K6, MAP2K7, MAP3K1, MAP3K10, MAP3K11, MAP3K12, MAP3K13, MAP3K14, MAP3K2, MAP3K3, MAP3K4, MAP3K5, MAP3K6, MAP3K7, MAP3K8, MAP3K9, MAP4K1, MAP4K2, MAP4K3, MAP4K4, MAP4K5, MAPK1, MAPK10, MAPK11, MAPK12, MAPK13, MAPK14, MAPK3, MAPK4, MAPK6, MAPK7, MAPK8, MAPK9, MAPKAPK2, MAPKAPK3, MAPKAPK5, MAX, MEF2A, MEF2B, MEF2C, MEF2D, MKNK1, MKNK2, MYC, NFKB1, NFKBIA, PAK1, PAK2, PDZGEF1, RAC1, RAF1, RELA, RIPK1, RPS6KA1, RPS6KA2, RPS6KA3, RPS6KA4, RPS6KA5, RPS6KB1, RPS6KB2, SHC1, SP1, STAT1, TGFB1, TGFB2, TGFB3, TGFBR1, TRADD, TRAF2 84 BRAF(24), DAXX(1), HRAS(1), IKBKB(1), MAP2K1(3), MAP2K2(1), MAP2K3(2), MAP3K1(1), MAP3K12(1), MAP3K14(1), MAP3K5(2), MAP3K9(2), MAP4K4(1), MAPK10(1), MAPK12(1), MAPK13(1), MAPK4(3), MAPK8(1), MAPK9(2), MAPKAPK3(1), MEF2B(1), MEF2C(1), MEF2D(1), MYC(1), RELA(1), RPS6KA1(3), RPS6KA2(1), RPS6KA4(1), SHC1(2), TRAF2(1) 5298061 64 32 42 7 28 4 4 25 3 0 0.000066 0.0016 0.18
6 HSA04320_DORSO_VENTRAL_AXIS_FORMATION Genes involved in dorso-ventral axis formation BRAF, CPEB1, EGFR, ERBB2, ERBB4, ETS1, ETS2, ETV6, ETV7, FMN2, GRB2, KRAS, MAP2K1, MAPK1, MAPK3, NOTCH1, NOTCH2, NOTCH3, NOTCH4, PIWIL1, PIWIL2, PIWIL3, PIWIL4, RAF1, SOS1, SOS2, SPIRE1, SPIRE2 28 BRAF(24), EGFR(1), ERBB4(3), ETS1(1), ETS2(1), ETV6(2), FMN2(3), MAP2K1(3), NOTCH2(4), NOTCH4(3), PIWIL1(1), PIWIL2(2), PIWIL4(2), SOS1(1), SOS2(2) 2938184 53 27 31 9 16 1 2 29 5 0 0.026 0.0021 0.18
7 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 CDKN2A(1), E2F1(2), MDM2(1), MYC(1), PIK3CA(1), PIK3R1(4), POLR1B(1), TP53(4) 1134716 15 13 15 1 3 1 3 3 5 0 0.023 0.0021 0.18
8 ERK5PATHWAY Signaling between a tissue and its innervating axon stimulates retrograde transport via Trk receptors, which activate Erk5, which induces transcription of anti-apoptotic factors. AKT1, CREB1, GRB2, HRAS, MAPK1, MAPK3, MAPK7, MEF2A, MEF2B, MEF2C, MEF2D, NTRK1, PIK3CA, PIK3R1, PLCG1, RPS6KA1, SHC1 17 HRAS(1), MEF2B(1), MEF2C(1), MEF2D(1), NTRK1(4), PIK3CA(1), PIK3R1(4), RPS6KA1(3), SHC1(2) 1061373 18 13 18 2 5 3 3 2 5 0 0.015 0.0024 0.19
9 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(1), KLRC1(1), MAP2K1(3), PIK3CA(1), PIK3R1(4), PTK2B(1), SYK(2), VAV1(2) 1042544 15 12 13 1 8 1 1 2 3 0 0.014 0.0039 0.27
10 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 CDKN2A(1), E2F1(2), MDM2(1), PRB1(5), TP53(4) 471635 13 9 13 1 7 1 2 1 2 0 0.02 0.0058 0.36

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 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 CDKN2A(1), E2F1(2), MDM2(1), MYC(1), PIK3CA(1), PIK3R1(4), POLR1B(1), TP53(4) 1134716 15 13 15 1 3 1 3 3 5 0 0.023 0.0021 0.75
2 ERK5PATHWAY Signaling between a tissue and its innervating axon stimulates retrograde transport via Trk receptors, which activate Erk5, which induces transcription of anti-apoptotic factors. AKT1, CREB1, GRB2, HRAS, MAPK1, MAPK3, MAPK7, MEF2A, MEF2B, MEF2C, MEF2D, NTRK1, PIK3CA, PIK3R1, PLCG1, RPS6KA1, SHC1 17 HRAS(1), MEF2B(1), MEF2C(1), MEF2D(1), NTRK1(4), PIK3CA(1), PIK3R1(4), RPS6KA1(3), SHC1(2) 1061373 18 13 18 2 5 3 3 2 5 0 0.015 0.0024 0.75
3 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(1), KLRC1(1), MAP2K1(3), PIK3CA(1), PIK3R1(4), PTK2B(1), SYK(2), VAV1(2) 1042544 15 12 13 1 8 1 1 2 3 0 0.014 0.0039 0.8
4 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 CDKN2A(1), E2F1(2), MDM2(1), PRB1(5), TP53(4) 471635 13 9 13 1 7 1 2 1 2 0 0.02 0.0058 0.89
5 MITRPATHWAY The MyoD/MEF2 transcription factors induce muscle cell differentiation and are repressed by the transcriptional repressor MITR. CAMK1, CAMK1G, HDAC9, MEF2A, MEF2B, MEF2C, MEF2D, MYOD1, YWHAH 9 CAMK1(1), CAMK1G(2), HDAC9(6), MEF2B(1), MEF2C(1), MEF2D(1) 421151 12 9 12 1 8 1 0 1 2 0 0.024 0.014 1
6 GSPATHWAY Activated G-protein coupled receptors stimulate cAMP production and thus activate protein kinase A, involved in a number of signal transduction pathways. ADCY1, GNAS, GNB1, GNGT1, PRKACA, PRKAR1A 6 ADCY1(3), GNAS(3), PRKACA(1), PRKAR1A(1) 366518 8 8 7 1 6 0 0 1 1 0 0.15 0.016 1
7 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 HRAS(1), IGF1R(1), IRS1(1), MAP2K1(3), PIK3CA(1), PIK3R1(4), SHC1(2), SOS1(1) 1068570 14 12 12 1 6 0 2 2 4 0 0.036 0.018 1
8 SA_TRKA_RECEPTOR The TrkA receptor binds nerve growth factor to activate MAP kinase pathways and promote cell growth. AKT1, AKT2, AKT3, ARHA, CDKN1A, ELK1, GRB2, HRAS, MAP2K1, MAP2K2, NGFB, NGFR, NTRK1, PIK3CA, PIK3CD, SHC1, SOS1 15 HRAS(1), MAP2K1(3), MAP2K2(1), NGFR(1), NTRK1(4), PIK3CA(1), SHC1(2), SOS1(1) 899557 14 12 12 1 8 2 1 2 1 0 0.013 0.021 1
9 HSA00130_UBIQUINONE_BIOSYNTHESIS Genes involved in ubiquinone biosynthesis COQ2, COQ3, COQ5, COQ6, COQ7, ND1, ND2, ND3, ND4, ND4L, ND5, ND6, NDUFA12, NDUFA13, NDUFB11 8 COQ3(2), COQ5(1), COQ6(1), NDUFA13(1) 224210 5 5 5 1 2 0 1 1 1 0 0.39 0.025 1
10 HSA00902_MONOTERPENOID_BIOSYNTHESIS Genes involved in monoterpenoid biosynthesis CYP2C19, CYP2C9 2 CYP2C19(7), CYP2C9(3) 113730 10 8 10 4 5 1 0 3 1 0 0.45 0.033 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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