Head and Neck Squamous Cell 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: HNSC-TP

  • Number of patients in set: 306

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:HNSC-TP.final_analysis_set.maf

  • Significantly mutated genes (q ≤ 0.1): 104

  • Mutations seen in COSMIC: 469

  • Significantly mutated genes in COSMIC territory: 8

  • Genes with clustered mutations (≤ 3 aa apart): 550

  • Significantly mutated genesets: 66

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

Mutation Preprocessing

  • Read 306 MAFs of type "Broad"

  • Total number of mutations in input MAFs: 74008

  • After removing 10 mutations outside chr1-24: 73998

  • After removing 1938 blacklisted mutations: 72060

  • After removing 4374 noncoding mutations: 67686

  • After collapsing adjacent/redundant mutations: 57601

Mutation Filtering

  • Number of mutations before filtering: 57601

  • After removing 872 mutations outside gene set: 56729

  • After removing 343 mutations outside category set: 56386

Results
Breakdown of Mutations by Type

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

type count
Frame_Shift_Del 1115
Frame_Shift_Ins 519
In_Frame_Del 299
In_Frame_Ins 42
Missense_Mutation 36355
Nonsense_Mutation 2876
Nonstop_Mutation 53
Silent 14127
Splice_Site 910
Translation_Start_Site 90
Total 56386
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 5984 498919062 0.000012 12 2.6 2.1
*Cp(A/C/T)->T 9123 4084447193 2.2e-06 2.2 0.48 1.7
C->(G/A) 14174 4583366255 3.1e-06 3.1 0.66 4.8
A->mut 7046 4404728973 1.6e-06 1.6 0.34 3.9
indel+null 5880 8988095228 6.5e-07 0.65 0.14 NaN
double_null 52 8988095228 5.8e-09 0.0058 0.0012 NaN
Total 42259 8988095228 4.7e-06 4.7 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: HNSC-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)->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_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: 104. 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 TP53 tumor protein p53 375773 238 207 146 5 41 27 39 40 84 7 <1.00e-15 <1.00e-15 NaN NaN <1.00e-15 <9.05e-12
2 NOTCH1 Notch homolog 1, translocation-associated (Drosophila) 1904576 61 57 61 4 10 10 9 6 26 0 <1.00e-15 2.83e-06 NaN NaN <1.00e-15 <9.05e-12
3 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 1003706 64 63 23 0 1 40 6 17 0 0 2.89e-15 6.29e-09 NaN NaN 2.89e-15 1.64e-11
4 CDKN2A cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4) 255389 61 61 27 0 2 2 2 6 48 1 3.89e-15 5.28e-08 NaN NaN 3.89e-15 1.64e-11
5 FAT1 FAT tumor suppressor homolog 1 (Drosophila) 4166666 80 72 80 2 1 5 7 6 53 8 5.33e-15 2.19e-06 NaN NaN 5.33e-15 1.64e-11
6 CASP8 caspase 8, apoptosis-related cysteine peptidase 533487 25 25 22 0 1 4 2 5 13 0 5.44e-15 0.000959 NaN NaN 5.44e-15 1.64e-11
7 JUB jub, ajuba homolog (Xenopus laevis) 357659 18 17 18 1 1 2 0 2 13 0 1.53e-14 0.0608 NaN NaN 1.53e-14 3.96e-11
8 MLL2 myeloid/lymphoid or mixed-lineage leukemia 2 4343439 57 55 57 3 4 7 7 2 34 3 8.49e-14 0.000263 NaN NaN 8.49e-14 1.92e-10
9 NFE2L2 nuclear factor (erythroid-derived 2)-like 2 546479 18 17 13 0 0 4 10 4 0 0 3.97e-11 0.0282 NaN NaN 3.97e-11 7.99e-08
10 BAGE2 B melanoma antigen family, member 2 105801 12 11 9 2 0 6 2 2 1 1 3.83e-10 0.129 NaN NaN 3.83e-10 6.93e-07
11 NSD1 nuclear receptor binding SET domain protein 1 2490988 36 33 36 1 0 2 8 4 20 2 1.08e-09 0.0169 NaN NaN 1.08e-09 1.69e-06
12 POTEC POTE ankyrin domain family, member C 471221 15 15 15 1 2 4 4 4 1 0 1.12e-09 0.0681 NaN NaN 1.12e-09 1.69e-06
13 HRAS v-Ha-ras Harvey rat sarcoma viral oncogene homolog 198292 11 10 6 0 2 2 6 1 0 0 2.33e-08 0.0221 NaN NaN 2.33e-08 3.24e-05
14 B2M beta-2-microglobulin 113810 7 7 6 0 0 1 1 1 4 0 4.50e-08 0.355 NaN NaN 4.50e-08 5.82e-05
15 POM121L12 POM121 transmembrane nucleoporin-like 12 264068 15 14 15 2 4 2 4 3 2 0 8.25e-08 0.104 NaN NaN 8.25e-08 9.95e-05
16 RAC1 ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) 189570 10 9 8 0 2 3 2 3 0 0 1.65e-07 0.0351 NaN NaN 1.65e-07 0.000187
17 ZNF804B zinc finger protein 804B 1240408 22 21 22 2 4 5 6 5 2 0 3.19e-07 0.0640 NaN NaN 3.19e-07 0.000339
18 OR2T12 olfactory receptor, family 2, subfamily T, member 12 294908 11 11 11 1 2 2 2 3 2 0 4.27e-07 0.104 NaN NaN 4.27e-07 0.000429
19 CDH10 cadherin 10, type 2 (T2-cadherin) 736566 24 23 24 4 0 3 12 8 1 0 1.16e-06 0.344 NaN NaN 1.16e-06 0.00110
20 KCNT2 potassium channel, subfamily T, member 2 1040701 17 17 16 1 2 1 6 3 5 0 1.54e-06 0.142 NaN NaN 1.54e-06 0.00134
21 RASA1 RAS p21 protein activator (GTPase activating protein) 1 928769 14 14 12 0 2 0 3 2 7 0 1.67e-06 0.0560 NaN NaN 1.67e-06 0.00134
22 EP300 E1A binding protein p300 2248955 25 25 22 1 3 7 4 5 6 0 1.69e-06 0.00726 NaN NaN 1.69e-06 0.00134
23 LCP1 lymphocyte cytosolic protein 1 (L-plastin) 593980 12 12 12 0 3 1 3 4 1 0 1.71e-06 0.0391 NaN NaN 1.71e-06 0.00134
24 PRAMEF11 PRAME family member 11 390027 10 10 9 0 2 1 5 2 0 0 1.84e-06 0.0783 NaN NaN 1.84e-06 0.00139
25 PRSS1 protease, serine, 1 (trypsin 1) 233784 8 8 7 1 0 4 1 2 1 0 2.68e-06 0.168 NaN NaN 2.68e-06 0.00194
26 FBXW7 F-box and WD repeat domain containing 7 757876 14 13 12 1 2 2 5 3 2 0 2.85e-06 0.179 NaN NaN 2.85e-06 0.00198
27 PEG3 paternally expressed 3 1345043 26 23 26 2 0 6 11 6 3 0 3.15e-06 0.0764 NaN NaN 3.15e-06 0.00208
28 ZNF99 zinc finger protein 99 949165 26 22 26 4 0 4 10 6 6 0 3.31e-06 0.461 NaN NaN 3.31e-06 0.00208
29 REG1A regenerating islet-derived 1 alpha (pancreatic stone protein, pancreatic thread protein) 159337 8 8 8 0 0 1 5 2 0 0 3.37e-06 0.151 NaN NaN 3.37e-06 0.00208
30 STEAP4 STEAP family member 4 425992 10 10 10 1 0 4 1 2 3 0 3.45e-06 0.174 NaN NaN 3.45e-06 0.00208
31 FCRL4 Fc receptor-like 4 485362 14 13 14 1 1 2 7 3 1 0 3.64e-06 0.140 NaN NaN 3.64e-06 0.00212
32 LRFN5 leucine rich repeat and fibronectin type III domain containing 5 664309 15 13 14 1 0 2 8 4 1 0 1.10e-05 0.134 NaN NaN 1.10e-05 0.00620
33 EPHA2 EPH receptor A2 868017 16 14 15 0 3 0 1 1 10 1 1.29e-05 0.0203 NaN NaN 1.29e-05 0.00705
34 POTEG POTE ankyrin domain family, member G 366329 11 10 11 0 1 2 6 0 2 0 1.39e-05 0.113 NaN NaN 1.39e-05 0.00737
35 CPXCR1 CPX chromosome region, candidate 1 219187 7 7 7 0 0 0 5 1 1 0 1.57e-05 0.368 NaN NaN 1.57e-05 0.00813
TP53

Figure S1.  This figure depicts the distribution of mutations and mutation types across the TP53 significant gene.

NOTCH1

Figure S2.  This figure depicts the distribution of mutations and mutation types across the NOTCH1 significant gene.

PIK3CA

Figure S3.  This figure depicts the distribution of mutations and mutation types across the PIK3CA significant gene.

CDKN2A

Figure S4.  This figure depicts the distribution of mutations and mutation types across the CDKN2A significant gene.

FAT1

Figure S5.  This figure depicts the distribution of mutations and mutation types across the FAT1 significant gene.

JUB

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

MLL2

Figure S7.  This figure depicts the distribution of mutations and mutation types across the MLL2 significant gene.

NFE2L2

Figure S8.  This figure depicts the distribution of mutations and mutation types across the NFE2L2 significant gene.

NSD1

Figure S9.  This figure depicts the distribution of mutations and mutation types across the NSD1 significant gene.

POTEC

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

HRAS

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

B2M

Figure S12.  This figure depicts the distribution of mutations and mutation types across the B2M significant gene.

POM121L12

Figure S13.  This figure depicts the distribution of mutations and mutation types across the POM121L12 significant gene.

RAC1

Figure S14.  This figure depicts the distribution of mutations and mutation types across the RAC1 significant gene.

ZNF804B

Figure S15.  This figure depicts the distribution of mutations and mutation types across the ZNF804B significant gene.

OR2T12

Figure S16.  This figure depicts the distribution of mutations and mutation types across the OR2T12 significant gene.

CDH10

Figure S17.  This figure depicts the distribution of mutations and mutation types across the CDH10 significant gene.

KCNT2

Figure S18.  This figure depicts the distribution of mutations and mutation types across the KCNT2 significant gene.

RASA1

Figure S19.  This figure depicts the distribution of mutations and mutation types across the RASA1 significant gene.

EP300

Figure S20.  This figure depicts the distribution of mutations and mutation types across the EP300 significant gene.

LCP1

Figure S21.  This figure depicts the distribution of mutations and mutation types across the LCP1 significant gene.

PRAMEF11

Figure S22.  This figure depicts the distribution of mutations and mutation types across the PRAMEF11 significant gene.

PRSS1

Figure S23.  This figure depicts the distribution of mutations and mutation types across the PRSS1 significant gene.

FBXW7

Figure S24.  This figure depicts the distribution of mutations and mutation types across the FBXW7 significant gene.

PEG3

Figure S25.  This figure depicts the distribution of mutations and mutation types across the PEG3 significant gene.

REG1A

Figure S26.  This figure depicts the distribution of mutations and mutation types across the REG1A significant gene.

STEAP4

Figure S27.  This figure depicts the distribution of mutations and mutation types across the STEAP4 significant gene.

FCRL4

Figure S28.  This figure depicts the distribution of mutations and mutation types across the FCRL4 significant gene.

LRFN5

Figure S29.  This figure depicts the distribution of mutations and mutation types across the LRFN5 significant gene.

EPHA2

Figure S30.  This figure depicts the distribution of mutations and mutation types across the EPHA2 significant gene.

POTEG

Figure S31.  This figure depicts the distribution of mutations and mutation types across the POTEG 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: 8. Number of genes displayed: 10

rank gene description n cos n_cos N_cos cos_ev p q
1 TP53 tumor protein p53 238 356 219 108936 45736 0 0
2 CDKN2A cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4) 61 332 60 101592 2905 0 0
3 HRAS v-Ha-ras Harvey rat sarcoma viral oncogene homolog 11 19 11 5814 2979 1.3e-13 2e-10
4 FBXW7 F-box and WD repeat domain containing 7 14 91 10 27846 183 5.8e-13 6.5e-10
5 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 64 220 54 67320 26364 1.2e-12 1e-09
6 PIK3R1 phosphoinositide-3-kinase, regulatory subunit 1 (alpha) 6 33 4 10098 3 2e-07 0.00015
7 PTPN14 protein tyrosine phosphatase, non-receptor type 14 13 3 2 918 2 9.3e-06 0.006
8 SCN9A sodium channel, voltage-gated, type IX, alpha subunit 10 4 2 1224 2 0.000016 0.0093
9 PTCH1 patched homolog 1 (Drosophila) 11 256 4 78336 5 0.00057 0.2
10 RB1 retinoblastoma 1 (including osteosarcoma) 9 267 4 81702 5 0.00067 0.2

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
8573 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 64 0 331 628 650 331 628 650
11744 TP53 tumor protein p53 238 0 321 853 2124 321 853 2124
5177 HRAS v-Ha-ras Harvey rat sarcoma viral oncogene homolog 11 0 18 45 45 18 45 45
7412 NFE2L2 nuclear factor (erythroid-derived 2)-like 2 18 0 13 38 60 13 38 60
4038 FBXW7 F-box and WD repeat domain containing 7 14 0 6 11 20 6 11 20
1567 C3orf59 chromosome 3 open reading frame 59 8 0 6 6 6 6 6 6
6601 MAPK1 mitogen-activated protein kinase 1 4 0 6 6 6 6 6 6
9578 RHOA ras homolog gene family, member A 4 0 6 6 6 6 6 6
1861 CASP8 caspase 8, apoptosis-related cysteine peptidase 25 0 5 8 19 5 8 19
7537 NOTCH1 Notch homolog 1, translocation-associated (Drosophila) 59 0 4 13 38 4 13 38

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: 66. 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 APOPTOSIS_GENMAPP APAF1, BAK1, BCL2L7P1, BAX, BCL2, BCL2L1, BID, BIRC2, BIRC3, BIRC4, CASP2, CASP3, CASP6, CASP7, CASP8, CASP9, CYCS, FADD, FAS, FASLG, GZMB, IKBKG, JUN, MAP2K4, MAP3K1, MAP3K14, MAPK10, MCL1, MDM2, MYC, NFKB1, NFKBIA, PARP1, PRF1, RELA, RIPK1, TNF, TNFRSF1A, TNFRSF1B, TNFSF10, TP53, TRADD, TRAF1, TRAF2 41 APAF1(9), BAX(1), BCL2(1), BCL2L1(2), BID(2), BIRC2(1), BIRC3(1), CASP3(1), CASP6(2), CASP7(1), CASP8(25), FADD(1), FAS(1), FASLG(2), GZMB(1), MAP2K4(1), MAP3K1(3), MAP3K14(2), MAPK10(3), MCL1(1), MDM2(2), MYC(4), NFKB1(2), PARP1(3), PRF1(3), RELA(1), RIPK1(2), TP53(238), TRAF2(1) 17088240 317 233 222 21 53 41 56 56 104 7 <1.00e-15 <1.00e-15 <6.16e-14
2 G1PATHWAY CDK4/6-cyclin D and CDK2-cyclin E phosphorylate Rb, which allows the transcription of genes needed for the G1/S cell cycle transition. ABL1, ATM, ATR, CCNA1, CCND1, CCNE1, CDC2, CDC25A, CDK2, CDK4, CDK6, CDKN1A, CDKN1B, CDKN2A, CDKN2B, DHFR, E2F1, GSK3B, HDAC1, MADH3, MADH4, RB1, SKP2, TFDP1, TGFB1, TGFB2, TGFB3, TP53 25 ATM(9), ATR(19), CCNA1(4), CCND1(2), CCNE1(3), CDK4(4), CDK6(1), CDKN1B(2), CDKN2A(61), DHFR(3), GSK3B(1), RB1(9), SKP2(2), TFDP1(3), TGFB1(1), TGFB2(2), TP53(238) 13736583 364 226 238 19 48 43 56 61 148 8 <1.00e-15 <1.00e-15 <6.16e-14
3 TELPATHWAY Telomerase is a ribonucleotide protein that adds telomeric repeats to the 3' ends of chromosomes. AKT1, BCL2, EGFR, G22P1, HSPCA, IGF1R, KRAS2, MYC, POLR2A, PPP2CA, PRKCA, RB1, TEP1, TERF1, TERT, TNKS, TP53, XRCC5 15 AKT1(2), BCL2(1), EGFR(14), IGF1R(7), MYC(4), POLR2A(9), PRKCA(2), RB1(9), TEP1(8), TERF1(3), TERT(1), TNKS(4), TP53(238), XRCC5(2) 12869416 304 223 212 29 49 41 60 52 95 7 7.27e-14 <1.00e-15 <6.16e-14
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 CCND1(2), CDK4(4), CDKN1B(2), CDKN2A(61), CFL1(2), E2F2(3), MDM2(2), PRB1(8), TP53(238) 3842593 322 217 195 12 44 34 49 50 137 8 <1.00e-15 <1.00e-15 <6.16e-14
5 PLK3PATHWAY Active Plk3 phosphorylates CDC25c, blocking the G2/M transition, and phosphorylates p53 to induce apoptosis. ATM, ATR, CDC25C, CHEK1, CHEK2, CNK, TP53, YWHAH 7 ATM(9), ATR(19), CHEK1(1), CHEK2(4), TP53(238), YWHAH(1) 7290074 272 213 180 10 43 35 47 52 88 7 1.48e-14 <1.00e-15 <6.16e-14
6 TERTPATHWAY hTERC, the RNA subunit of telomerase, and hTERT, the catalytic protein subunit, are required for telomerase activity and are overexpressed in many cancers. HDAC1, MAX, MYC, SP1, SP3, TP53, WT1, ZNF42 7 MAX(1), MYC(4), SP1(1), SP3(1), TP53(238) 3219260 245 207 153 7 41 28 42 42 85 7 <1.00e-15 <1.00e-15 <6.16e-14
7 IGF1PATHWAY Growth factor IGF-1 stimulates growth and inhibits apoptosis by activating the MAP kinase pathway in a variety of cell types. CSNK2A1, ELK1, FOS, GRB2, HRAS, IGF1, IGF1R, IRS1, JUN, MAP2K1, MAPK3, MAPK8, PIK3CA, PIK3R1, PTPN11, RAF1, RASA1, SHC1, SOS1, SRF 20 CSNK2A1(6), ELK1(1), FOS(1), HRAS(11), IGF1R(7), IRS1(1), MAP2K1(4), MAPK8(4), PIK3CA(64), PIK3R1(6), PTPN11(1), RAF1(2), RASA1(14), SHC1(1), SOS1(8) 11293994 131 109 83 5 11 47 32 24 17 0 2.07e-12 <1.00e-15 <6.16e-14
8 NGFPATHWAY Nerve growth factor (NGF) stimulates neural survival and proliferation via the TrkA and p75 receptors, which induce DAG and IP3 production and activate Ras. CSNK2A1, DPM2, ELK1, FOS, GRB2, HRAS, JUN, KLK2, MAP2K1, MAPK3, MAPK8, NGFB, NGFR, PIK3CA, PIK3R1, PLCG1, RAF1, SHC1, SOS1 18 CSNK2A1(6), ELK1(1), FOS(1), HRAS(11), MAP2K1(4), MAPK8(4), NGFR(1), PIK3CA(64), PIK3R1(6), PLCG1(5), RAF1(2), SHC1(1), SOS1(8) 8695189 114 93 68 3 9 46 29 21 9 0 1.09e-12 <1.00e-15 <6.16e-14
9 TRKAPATHWAY Nerve growth factor (NGF) promotes neuronal survival and proliferation by binding its receptor TrkA, which activates PI3K/AKT, Ras, and the MAP kinase pathway. AKT1, DPM2, GRB2, HRAS, KLK2, NGFB, NTRK1, PIK3CA, PIK3R1, PLCG1, PRKCA, PRKCB1, SHC1, SOS1 12 AKT1(2), HRAS(11), NTRK1(3), PIK3CA(64), PIK3R1(6), PLCG1(5), PRKCA(2), SHC1(1), SOS1(8) 7103380 102 87 56 5 6 49 21 23 3 0 4.12e-10 <1.00e-15 <6.16e-14
10 AKTPATHWAY Second messenger PIP3 promotes cell survival by activating the anti-apoptotic kinase AKT. AKT1, BAD, CASP9, CHUK, FOXO1A, FOXO3A, GH1, GHR, HSPCA, MLLT7, NFKB1, NFKBIA, PDPK1, PIK3CA, PIK3R1, PPP2CA, RELA, TNFSF6, YWHAH 14 AKT1(2), BAD(1), CHUK(3), GH1(1), GHR(4), NFKB1(2), PDPK1(2), PIK3CA(64), PIK3R1(6), RELA(1), YWHAH(1) 6437782 87 81 46 4 3 49 8 23 4 0 2.86e-09 <1.00e-15 <6.16e-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 HSA00902_MONOTERPENOID_BIOSYNTHESIS Genes involved in monoterpenoid biosynthesis CYP2C19, CYP2C9 2 CYP2C19(3), CYP2C9(5) 922599 8 8 8 0 0 3 4 1 0 0 0.087 0.052 1
2 HSA00627_1,4_DICHLOROBENZENE_DEGRADATION Genes involved in 1,4-dichlorobenzene degradation CMBL 1 CMBL(2) 231812 2 2 2 0 0 0 0 0 2 0 0.66 0.12 1
3 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(12), GNAS(6), GNB1(2), PRKACA(4), PRKAR1A(2) 2991458 26 23 26 2 10 3 9 4 0 0 0.019 0.16 1
4 BLOOD_GROUP_GLYCOLIPID_BIOSYNTHESIS_NEOLACTOSERIES ABO, B3GNT1, FUT1, FUT2, FUT9, GCNT2, ST8SIA1 7 ABO(2), B3GNT1(1), FUT1(1), FUT2(2), FUT9(10), GCNT2(4), ST8SIA1(2) 2797416 22 21 22 4 2 7 10 2 1 0 0.12 0.18 1
5 ACETAMINOPHENPATHWAY Acetaminophen selectively inhibits Cox-3, which is localized to the brain, and yields the toxic metabolite NAPQI when processed by CAR in the liver. CYP1A2, CYP2E1, CYP3A, NR1I3, PTGS1, PTGS2 5 CYP1A2(4), CYP2E1(5), PTGS1(6), PTGS2(2) 2433197 17 15 17 2 2 1 9 0 5 0 0.16 0.26 1
6 HSA00550_PEPTIDOGLYCAN_BIOSYNTHESIS Genes involved in peptidoglycan biosynthesis GLUL, PGLYRP2 2 GLUL(2), PGLYRP2(3) 829283 5 5 5 1 1 2 0 1 1 0 0.39 0.32 1
7 BETAOXIDATIONPATHWAY Beta-Oxidation of Fatty Acids ACADL, ACADM, ACADS, ACAT1, ECHS1, HADHA 6 ACADL(2), ACADM(3), ACADS(2), ECHS1(2), HADHA(3) 2467452 12 12 12 1 2 2 4 3 1 0 0.13 0.34 1
8 FBW7PATHWAY Cyclin E interacts with cell cycle checkpoint kinase cdk2 to allow transcription of genes required for S phase, including transcription of additional cyclin E. CCNE1, CDC34, CDK2, CUL1, E2F1, FBXW7, RB1, SKP1A, TFDP1 7 CCNE1(3), CDC34(1), CUL1(6), RB1(9), TFDP1(3) 2976526 22 21 22 4 3 4 2 2 11 0 0.16 0.34 1
9 NGFPATHWAY Nerve growth factor (NGF) stimulates neural survival and proliferation via the TrkA and p75 receptors, which induce DAG and IP3 production and activate Ras. CSNK2A1, DPM2, ELK1, FOS, GRB2, HRAS, JUN, KLK2, MAP2K1, MAPK3, MAPK8, NGFB, NGFR, PIK3CA, PIK3R1, PLCG1, RAF1, SHC1, SOS1 16 CSNK2A1(6), ELK1(1), FOS(1), MAP2K1(4), MAPK8(4), NGFR(1), PIK3R1(6), PLCG1(5), RAF1(2), SHC1(1), SOS1(8) 7493191 39 35 39 3 6 4 17 3 9 0 0.0092 0.39 1
10 FXRPATHWAY The nuclear receptor transcription factors FXR and LXR are activated by cholesterol metabolites and regulate cholesterol homeostasis. FABP6, LDLR, NR0B2, NR1H3, NR1H4, RXRA 6 FABP6(2), LDLR(3), NR0B2(1), NR1H4(5), RXRA(4) 2480469 15 15 15 1 2 2 6 1 4 0 0.1 0.4 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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