Skin Cutaneous Melanoma: Mutation Analysis (MutSig v2.0)
(NRAS_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-NRAS_Hotspot_Mutants

  • Number of patients in set: 62

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-NRAS_Hotspot_Mutants.final_analysis_set.maf

  • Significantly mutated genes (q ≤ 0.1): 62

  • Mutations seen in COSMIC: 190

  • Significantly mutated genes in COSMIC territory: 10

  • Genes with clustered mutations (≤ 3 aa apart): 221

  • Significantly mutated genesets: 2

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

Mutation Preprocessing

  • Read 62 MAFs of type "Broad"

  • Total number of mutations in input MAFs: 46988

  • After removing 261 blacklisted mutations: 46727

  • After removing 895 noncoding mutations: 45832

Mutation Filtering

  • Number of mutations before filtering: 45832

  • After removing 572 mutations outside gene set: 45260

  • After removing 13 mutations outside category set: 45247

  • After removing 3 "impossible" mutations in

  • gene-patient-category bins of zero coverage: 44659

Results
Breakdown of Mutations by Type

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

type count
Frame_Shift_Del 328
Frame_Shift_Ins 88
In_Frame_Del 158
In_Frame_Ins 17
Missense_Mutation 27459
Nonsense_Mutation 1812
Nonstop_Mutation 8
Silent 14879
Splice_Site 485
Translation_Start_Site 13
Total 45247
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 20356 494333534 0.000041 41 2.4 1.6
(A/G)p*C->T 2339 414978099 5.6e-06 5.6 0.33 1.9
A->G 1355 877421330 1.5e-06 1.5 0.091 2.3
transver 3420 1786732963 1.9e-06 1.9 0.11 5
indel+null 2884 1786732963 1.6e-06 1.6 0.095 NaN
double_null 13 1786732963 7.3e-09 0.0073 0.00043 NaN
Total 30367 1786732963 0.000017 17 1 3.5
Target Coverage for Each Individual

The x axis represents the samples. The y axis represents the exons, one row per exon, and they are sorted by average coverage across samples. For exons with exactly the same average coverage, they are sorted next by the %GC of the exon. (The secondary sort is especially useful for the zero-coverage exons at the bottom).

Figure 1. 

Distribution of Mutation Counts, Coverage, and Mutation Rates Across Samples

Figure 2.  Patients counts and rates file used to generate this plot: SKCM-NRAS_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: 62. 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 NRAS neuroblastoma RAS viral (v-ras) oncogene homolog 36331 62 62 6 0 0 1 22 39 0 0 1.2e-15 2.2e-07 2e-06 0 <1.00e-15 <1.81e-11
2 CDKN2A cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4) 55401 12 12 8 0 3 0 0 0 9 0 3.2e-12 0.018 0.001 0.0012 1.28e-13 1.15e-09
3 TP53 tumor protein p53 74456 13 13 12 0 6 0 1 1 5 0 4.8e-11 0.014 0.4 0.017 2.31e-11 1.39e-07
4 MUM1L1 melanoma associated antigen (mutated) 1-like 1 77235 14 13 14 1 9 1 1 3 0 0 6.5e-12 0.052 0.78 1 1.74e-10 7.86e-07
5 CD163L1 CD163 molecule-like 1 272450 27 21 25 3 18 3 0 2 4 0 6.7e-10 0.02 0.39 1 1.48e-08 5.34e-05
6 PSG4 pregnancy specific beta-1-glycoprotein 4 79523 15 12 12 1 13 0 0 2 0 0 1.6e-07 0.0074 0.78 0.023 7.40e-08 0.000223
7 PPP6C protein phosphatase 6, catalytic subunit 62508 10 10 9 1 6 0 0 0 4 0 3.2e-08 0.18 0.13 0.22 1.39e-07 0.000359
8 ZNF99 zinc finger protein 99 188343 18 16 16 2 13 3 0 2 0 0 3e-08 0.063 0.26 0.3 1.80e-07 0.000406
9 KHDRBS2 KH domain containing, RNA binding, signal transduction associated 2 62617 10 10 9 0 5 3 0 2 0 0 6.9e-08 0.065 0.57 0.34 4.27e-07 0.000857
10 POTEG POTE ankyrin domain family, member G 69185 13 10 9 1 11 1 0 0 1 0 6.9e-07 0.062 0.9 0.057 7.13e-07 0.00129
11 MARCO macrophage receptor with collagenous structure 90932 14 13 14 1 13 0 0 1 0 0 2.2e-07 0.032 0.22 0.28 1.12e-06 0.00184
12 SGCZ sarcoglycan zeta 55301 10 9 9 0 7 0 0 1 2 0 2.9e-07 0.016 0.37 0.3 1.50e-06 0.00226
13 GLRB glycine receptor, beta 90035 11 10 10 1 7 1 1 2 0 0 1.8e-07 0.058 0.37 0.53 1.65e-06 0.00230
14 OR2W1 olfactory receptor, family 2, subfamily W, member 1 59039 9 8 9 0 7 0 0 1 1 0 9e-06 0.0092 0.44 0.025 3.71e-06 0.00478
15 C4orf22 chromosome 4 open reading frame 22 44053 7 7 5 1 6 1 0 0 0 0 0.000031 0.19 0.6 0.017 8.10e-06 0.00975
16 UGT2B28 UDP glucuronosyltransferase 2 family, polypeptide B28 91580 11 11 11 1 10 0 0 0 1 0 1.4e-06 0.07 0.56 0.72 1.48e-05 0.0167
17 ZNF676 zinc finger protein 676 108628 12 11 12 2 10 0 0 1 0 1 2.7e-06 0.15 0.95 0.4 1.62e-05 0.0172
18 LIPI lipase, member I 90445 9 9 9 1 6 0 2 0 1 0 3.4e-06 0.17 0.44 0.35 1.74e-05 0.0175
19 CADM2 cell adhesion molecule 2 80135 8 8 8 0 5 3 0 0 0 0 7.8e-06 0.058 0.87 0.26 2.80e-05 0.0252
20 CDH9 cadherin 9, type 2 (T1-cadherin) 145105 11 11 10 0 8 0 0 2 1 0 0.000014 0.034 0.44 0.14 2.87e-05 0.0252
21 OR52E2 olfactory receptor, family 52, subfamily E, member 2 56515 7 7 6 3 6 0 0 1 0 0 0.0014 0.28 0.92 0.0015 2.93e-05 0.0252
22 CLEC5A C-type lectin domain family 5, member A 31770 6 5 6 2 4 0 1 1 0 0 0.0004 0.44 0.22 0.0063 3.53e-05 0.0286
23 HIST1H2AA histone cluster 1, H2aa 24800 5 5 5 0 2 1 0 1 1 0 4.4e-06 0.21 0.83 0.6 3.64e-05 0.0286
24 KIAA1257 KIAA1257 73671 8 8 7 1 7 0 0 0 1 0 9e-05 0.12 0.56 0.031 3.85e-05 0.0289
25 SPOCK3 sparc/osteonectin, cwcv and kazal-like domains proteoglycan (testican) 3 80077 9 9 8 1 8 0 0 1 0 0 0.000018 0.2 0.98 0.16 4.05e-05 0.0290
26 PCDH18 protocadherin 18 209409 18 16 15 3 14 1 1 2 0 0 0.000017 0.066 0.039 0.18 4.17e-05 0.0290
27 OR2G6 olfactory receptor, family 2, subfamily G, member 6 59195 10 10 10 2 9 0 0 0 1 0 9.1e-06 0.019 0.18 0.39 4.78e-05 0.0320
28 STXBP5L syntaxin binding protein 5-like 216617 18 14 17 1 14 1 1 2 0 0 5.4e-06 0.029 0.36 0.69 5.02e-05 0.0324
29 CNGB3 cyclic nucleotide gated channel beta 3 152769 18 15 15 4 12 2 1 0 3 0 6.7e-06 0.18 0.7 0.59 5.37e-05 0.0335
30 HHIPL2 HHIP-like 2 137081 5 4 4 1 3 0 0 2 0 0 0.11 0.4 0.18 0.000046 6.58e-05 0.0396
31 ZBBX zinc finger, B-box domain containing 148726 11 11 9 1 10 0 1 0 0 0 0.000067 0.13 1 0.082 7.21e-05 0.0403
32 OR10G8 olfactory receptor, family 10, subfamily G, member 8 57826 7 6 7 0 1 1 2 3 0 0 8.5e-06 0.092 0.65 0.65 7.29e-05 0.0403
33 UGT2B4 UDP glucuronosyltransferase 2 family, polypeptide B4 95458 12 11 12 2 9 0 0 0 2 1 5.6e-06 0.14 0.71 1 7.36e-05 0.0403
34 KRT78 keratin 78 91579 8 7 7 0 6 1 0 0 1 0 0.0015 0.0057 0.039 0.004 7.77e-05 0.0412
35 C1QTNF9 C1q and tumor necrosis factor related protein 9 51896 6 6 6 1 4 1 0 1 0 0 0.00024 0.32 0.84 0.026 8.01e-05 0.0412
NRAS

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

CDKN2A

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

TP53

Figure S3.  This figure depicts the distribution of mutations and mutation types across the TP53 significant gene.

MUM1L1

Figure S4.  This figure depicts the distribution of mutations and mutation types across the MUM1L1 significant gene.

CD163L1

Figure S5.  This figure depicts the distribution of mutations and mutation types across the CD163L1 significant gene.

PSG4

Figure S6.  This figure depicts the distribution of mutations and mutation types across the PSG4 significant gene.

PPP6C

Figure S7.  This figure depicts the distribution of mutations and mutation types across the PPP6C significant gene.

KHDRBS2

Figure S8.  This figure depicts the distribution of mutations and mutation types across the KHDRBS2 significant gene.

POTEG

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

MARCO

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

SGCZ

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

GLRB

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

OR2W1

Figure S13.  This figure depicts the distribution of mutations and mutation types across the OR2W1 significant gene.

C4orf22

Figure S14.  This figure depicts the distribution of mutations and mutation types across the C4orf22 significant gene.

UGT2B28

Figure S15.  This figure depicts the distribution of mutations and mutation types across the UGT2B28 significant gene.

ZNF676

Figure S16.  This figure depicts the distribution of mutations and mutation types across the ZNF676 significant gene.

LIPI

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

CADM2

Figure S18.  This figure depicts the distribution of mutations and mutation types across the CADM2 significant gene.

CDH9

Figure S19.  This figure depicts the distribution of mutations and mutation types across the CDH9 significant gene.

OR52E2

Figure S20.  This figure depicts the distribution of mutations and mutation types across the OR52E2 significant gene.

CLEC5A

Figure S21.  This figure depicts the distribution of mutations and mutation types across the CLEC5A significant gene.

HIST1H2AA

Figure S22.  This figure depicts the distribution of mutations and mutation types across the HIST1H2AA significant gene.

KIAA1257

Figure S23.  This figure depicts the distribution of mutations and mutation types across the KIAA1257 significant gene.

SPOCK3

Figure S24.  This figure depicts the distribution of mutations and mutation types across the SPOCK3 significant gene.

PCDH18

Figure S25.  This figure depicts the distribution of mutations and mutation types across the PCDH18 significant gene.

OR2G6

Figure S26.  This figure depicts the distribution of mutations and mutation types across the OR2G6 significant gene.

STXBP5L

Figure S27.  This figure depicts the distribution of mutations and mutation types across the STXBP5L significant gene.

CNGB3

Figure S28.  This figure depicts the distribution of mutations and mutation types across the CNGB3 significant gene.

HHIPL2

Figure S29.  This figure depicts the distribution of mutations and mutation types across the HHIPL2 significant gene.

ZBBX

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

OR10G8

Figure S31.  This figure depicts the distribution of mutations and mutation types across the OR10G8 significant gene.

UGT2B4

Figure S32.  This figure depicts the distribution of mutations and mutation types across the UGT2B4 significant gene.

KRT78

Figure S33.  This figure depicts the distribution of mutations and mutation types across the KRT78 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 NRAS neuroblastoma RAS viral (v-ras) oncogene homolog 62 33 62 2046 77092 6.7e-16 3e-12
2 TP53 tumor protein p53 13 356 13 22072 1809 6.4e-15 1.5e-11
3 CDKN2A cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4) 12 332 12 20584 513 1.1e-14 1.6e-11
4 IDH1 isocitrate dehydrogenase 1 (NADP+), soluble 5 5 4 310 5968 3.1e-11 3.5e-08
5 EPHA7 EPH receptor A7 14 13 3 806 3 4.2e-07 0.00038
6 OR6C74 olfactory receptor, family 6, subfamily C, member 74 2 1 2 62 2 5.5e-07 0.00041
7 STK19 serine/threonine kinase 19 4 2 2 124 4 2.2e-06 0.0014
8 IFITM3 interferon induced transmembrane protein 3 (1-8U) 3 3 2 186 2 5e-06 0.0028
9 FGFR2 fibroblast growth factor receptor 2 (bacteria-expressed kinase, keratinocyte growth factor receptor, craniofacial dysostosis 1, Crouzon syndrome, Pfeiffer syndrome, Jackson-Weiss syndrome) 10 51 3 3162 3 0.000025 0.012
10 EPHA6 EPH receptor A6 15 8 2 496 2 0.000035 0.016

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
6208 NRAS neuroblastoma RAS viral (v-ras) oncogene homolog 62 0 1491 1495 1495 1491 1495 1495
2648 DNAH5 dynein, axonemal, heavy chain 5 85 0 13 18 35 13 18 35
9319 THSD7B thrombospondin, type I, domain containing 7B 38 0 10 11 15 10 11 15
9762 TTN titin 251 0 9 13 20 9 13 20
9585 TPTE transmembrane phosphatase with tensin homology 21 0 8 10 13 8 10 13
5790 MUC16 mucin 16, cell surface associated 182 0 7 10 27 7 10 27
7472 PSG4 pregnancy specific beta-1-glycoprotein 4 15 0 7 9 12 7 9 12
4293 IDH1 isocitrate dehydrogenase 1 (NADP+), soluble 5 0 6 6 6 6 6 6
6115 NLRP5 NLR family, pyrin domain containing 5 17 0 4 6 7 4 6 7
6858 PCLO piccolo (presynaptic cytomatrix protein) 64 0 3 7 26 3 7 26

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 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(1), CDKN1A(3), CDKN2A(12), E2F1(1), E2F2(2), MDM2(1), NXT1(1), PRB1(4), TP53(13) 769500 38 25 33 2 16 2 2 2 16 0 0.000016 1.1e-07 0.000068
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(3), CDKN2A(12), E2F1(1), MDM2(1), MYC(2), PIK3CA(1), POLR1A(3), POLR1B(1), RAC1(3), RB1(3), TBX2(3), TP53(13) 1849356 46 30 41 3 20 3 2 4 17 0 0.000016 0.00011 0.034
3 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(3), CCNE2(3), CDK4(1), CDKN2A(12), E2F1(1), E2F2(2), PRB1(4) 822258 26 20 22 2 14 0 1 2 9 0 0.00096 0.0014 0.28
4 FOSBPATHWAY FOSB gene expression and drug abuse CDK5, FOSB, GRIA2, JUND, PPP1R1B 5 CDK5(2), GRIA2(11), PPP1R1B(1) 332784 14 13 14 3 6 1 0 4 3 0 0.19 0.003 0.37
5 P53PATHWAY p53 induces cell cycle arrest or apoptosis under conditions of DNA damage. APAF1, ATM, BAX, BCL2, CCND1, CCNE1, CDK2, CDK4, CDKN1A, E2F1, GADD45A, MDM2, PCNA, RB1, TIMP3, TP53 16 APAF1(2), ATM(4), BAX(2), BCL2(1), CDK4(1), CDKN1A(3), E2F1(1), MDM2(1), RB1(3), TIMP3(1), TP53(13) 1642639 32 24 31 3 12 4 2 3 11 0 0.0032 0.003 0.37
6 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 ABL1(3), ATM(4), ATR(4), CCNA1(3), CDC25A(3), CDK4(1), CDKN1A(3), CDKN2A(12), E2F1(1), RB1(3), SKP2(1), TFDP1(1), TGFB1(1), TGFB3(1), TP53(13) 2749707 54 33 49 7 24 3 3 3 21 0 0.00022 0.0036 0.37
7 SLRPPATHWAY Small leucine-rich proteoglycans (SLRPs) interact with and reorganize collagen fibers in the extracellular matrix. BGN, DCN, DSPG3, FMOD, KERA, LUM 5 BGN(1), DCN(4), FMOD(2), KERA(4), LUM(2) 319453 13 12 13 1 11 0 2 0 0 0 0.008 0.0091 0.8
8 TIDPATHWAY On ligand binding, interferon gamma receptors stimulate JAK2 kinase to phosphorylate STAT transcription factors, which promote expression of interferon responsive genes. DNAJA3, HSPA1A, IFNG, IFNGR1, IFNGR2, IKBKB, JAK2, LIN7A, NFKB1, NFKBIA, RB1, RELA, TIP-1, TNF, TNFRSF1A, TNFRSF1B, TP53, USH1C, WT1 18 DNAJA3(2), IFNGR1(3), IFNGR2(1), JAK2(1), LIN7A(3), NFKB1(3), RB1(3), RELA(2), TNFRSF1A(1), TNFRSF1B(2), TP53(13), USH1C(3) 1644576 37 29 36 6 15 3 2 6 11 0 0.018 0.017 1
9 1_AND_2_METHYLNAPHTHALENE_DEGRADATION ADH1A, ADH1A, ADH1B, ADH1C, ADH1B, ADH1C, ADH4, ADH6, ADH7, ADHFE1 7 ADH1A(2), ADH1B(6), ADH1C(8), ADH4(2), ADH7(5), ADHFE1(3) 515247 26 22 24 6 19 1 2 3 1 0 0.037 0.021 1
10 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 MYC(2), TP53(13) 647120 15 14 14 0 8 0 1 1 5 0 0.0055 0.026 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 FOSBPATHWAY FOSB gene expression and drug abuse CDK5, FOSB, GRIA2, JUND, PPP1R1B 5 CDK5(2), GRIA2(11), PPP1R1B(1) 332784 14 13 14 3 6 1 0 4 3 0 0.19 0.003 1
2 SLRPPATHWAY Small leucine-rich proteoglycans (SLRPs) interact with and reorganize collagen fibers in the extracellular matrix. BGN, DCN, DSPG3, FMOD, KERA, LUM 5 BGN(1), DCN(4), FMOD(2), KERA(4), LUM(2) 319453 13 12 13 1 11 0 2 0 0 0 0.008 0.0091 1
3 1_AND_2_METHYLNAPHTHALENE_DEGRADATION ADH1A, ADH1A, ADH1B, ADH1C, ADH1B, ADH1C, ADH4, ADH6, ADH7, ADHFE1 6 ADH1A(2), ADH1C(8), ADH4(2), ADH7(5), ADHFE1(3) 443633 20 17 18 5 14 1 1 3 1 0 0.1 0.088 1
4 SA_FAS_SIGNALING The TNF-type receptor Fas induces apoptosis on ligand binding. BCL2, CASP3, CASP8, CFL1, CFLAR, P11, PDE6D, TNFRSF6, TNFSF6 6 BCL2(1), CASP3(1), CASP8(2), CFLAR(3), PDE6D(1) 357732 8 8 8 1 3 1 1 2 1 0 0.21 0.11 1
5 HSA00401_NOVOBIOCIN_BIOSYNTHESIS Genes involved in novobiocin biosynthesis GOT1, GOT2, TAT 3 GOT2(3), TAT(5) 240405 8 7 8 3 4 1 1 0 2 0 0.37 0.11 1
6 HSA00627_1,4_DICHLOROBENZENE_DEGRADATION Genes involved in 1,4-dichlorobenzene degradation CMBL 1 CMBL(2) 46983 2 2 2 0 2 0 0 0 0 0 0.46 0.14 1
7 O_GLYCAN_BIOSYNTHESIS GALNT1, GALNT10, GALNT2, GALNT3, GALNT4, GALNT6, GALNT7, GALNT8, GALNT9, GCNT1, SIAT4A, SIAT4B, ST3GAL1, ST3GAL2, ST3GAL4, WBSCR17 14 GALNT1(2), GALNT2(4), GALNT3(1), GALNT4(2), GALNT6(2), GALNT8(8), GALNT9(2), GCNT1(1), ST3GAL1(2), ST3GAL4(1), WBSCR17(12) 1319494 37 27 37 7 28 3 1 4 1 0 0.004 0.28 1
8 HSA00830_RETINOL_METABOLISM Genes involved in retinol metabolism ALDH1A1, ALDH1A2, BCMO1, RDH5 4 ALDH1A1(2), ALDH1A2(2), BCMO1(5), RDH5(1) 356527 10 10 9 3 8 0 0 2 0 0 0.21 0.29 1
9 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 13 CDK4(1), CDKN1A(3), E2F1(1), E2F2(2), MDM2(1), NXT1(1), PRB1(4) 639643 13 11 13 2 7 2 1 1 2 0 0.048 0.3 1
10 HSA00472_D_ARGININE_AND_D_ORNITHINE_METABOLISM Genes involved in D-arginine and D-ornithine metabolism DAO 1 DAO(1) 65308 1 1 1 0 0 0 0 1 0 0 0.83 0.31 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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