Skin Cutaneous Melanoma: Mutation Analysis (MutSigCV v0.9)
(All_Metastatic 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. MutSigCV v0.9 was used to generate the results found in this report.

  • Working with individual set: SKCM-All_Metastatic

  • Number of patients in set: 228

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
Results
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_Metastatic.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:

  • nnon = 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

  • nflank = number of noncoding mutations from this gene's flanking region, across the individual set

  • nsil = number of silent mutations in this gene across the individual set

  • p = p-value (overall)

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

Table 1.  Get Full Table A Ranked List of Significantly Mutated Genes. Number of significant genes found: 46. 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).

gene Nnon Nsil Nflank nnon npat nsite nsil nflank nnei fMLE p score time q
NRAS 105108 27816 1722 67 67 9 1 0 20 0.77 0 210 0.16 0
BRAF 393756 112404 7119 123 117 17 3 0 19 0.75 1e-15 300 0.16 9.1e-12
PTEN 222072 53352 3654 18 18 16 0 0 20 0.58 7.1e-15 86 0.21 3.8e-11
CDKN2A 137256 38988 1302 33 33 15 1 0 6 0.61 8.3e-15 150 0.16 3.8e-11
TP53 215460 62928 4326 39 35 33 1 0 4 1 1.4e-13 110 0.18 5.1e-10
DSG1 564984 162792 6300 56 39 49 10 0 20 0.63 4.6e-09 84 0.16 0.000014
PPP6C 168264 46056 2751 19 18 14 2 0 20 0.69 7e-09 57 0.21 0.000018
PPIAL4G 88920 23712 504 12 12 9 7 0 20 0.71 1.6e-06 37 0.15 0.0036
AOAH 333108 79800 8568 22 21 20 9 0 20 0.66 3.1e-06 55 0.16 0.0063
EIF2B1 191292 54720 4557 9 9 3 3 0 20 0.54 4.2e-06 44 0.15 0.0077
IL32 93024 24396 2289 9 9 6 3 0 20 0.96 6.7e-06 39 0.16 0.011
OR51S1 164388 56088 567 30 27 21 8 0 20 1.6 8e-06 54 0.16 0.012
LCE1B 63156 18240 504 12 12 12 0 0 20 1.2 8.2e-06 35 0.15 0.012
MS4A2 134976 39216 2751 10 10 10 1 0 11 0.25 0.000012 32 0.21 0.014
LRTM1 181488 54948 1323 28 23 27 14 0 20 1 0.000012 48 0.15 0.014
TCEB3C 174192 56088 231 31 26 23 9 0 20 1.5 0.000014 58 0.17 0.016
DNAH7 2208636 582768 26439 168 83 152 60 0 20 1.6 2e-05 150 0.16 0.02
GPR141 162792 46056 504 14 14 10 5 0 20 0.56 0.000021 37 0.15 0.02
SCN5A 1009356 294804 7539 83 57 80 43 0 20 1.1 0.000022 100 0.3 0.02
LRRC4C 336528 100776 504 39 33 34 14 0 13 1.5 0.000022 72 0.16 0.02
KIAA2022 808032 215916 1092 58 44 52 23 0 11 0.93 0.000041 86 0.33 0.036
TCHHL1 484500 134292 924 46 31 44 8 0 17 0.61 5e-05 56 0.19 0.041
TUBAL3 237576 70224 1743 11 10 11 5 0 20 0.21 0.000053 27 0.15 0.042
MPP7 319428 83904 6615 31 25 27 5 0 8 0.89 0.000057 55 0.16 0.043
C1QTNF9 149340 45144 1323 14 14 12 3 0 19 0.61 0.000061 36 0.15 0.045
KCNB2 484500 138852 924 68 52 55 30 0 20 2.1 0.000066 84 0.17 0.046
B2M 65436 18240 1344 5 5 4 0 0 20 0.89 0.000067 28 0.15 0.046
FAM113B 196080 62928 378 21 20 18 17 0 20 0.87 0.000084 45 0.16 0.055
PROL1 126768 43548 882 24 21 19 7 0 20 1.1 0.000088 39 0.16 0.056
C18orf26 112404 33288 1344 16 14 15 6 0 20 1.3 0.000098 39 0.15 0.06
NF1 2145936 601464 24864 45 32 43 7 0 0 0.29 0.00012 110 0.19 0.07
GK2 292068 85956 483 35 29 30 5 0 20 1.7 0.00012 60 0.15 0.071
OR4E2 163476 49932 546 21 20 15 15 0 20 1.1 0.00013 40 0.16 0.072
SV2B 376200 100320 5082 29 25 26 9 0 20 1 0.00014 55 0.21 0.072
AMHR2 288192 83904 4221 15 14 14 3 0 20 0.7 0.00014 47 0.15 0.072
NRAS

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

BRAF

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

PTEN

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

CDKN2A

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

TP53

Figure S5.  This figure depicts the distribution of mutations and mutation types across the TP53 significant gene.

DSG1

Figure S6.  This figure depicts the distribution of mutations and mutation types across the DSG1 significant gene.

PPP6C

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

PPIAL4G

Figure S8.  This figure depicts the distribution of mutations and mutation types across the PPIAL4G significant gene.

EIF2B1

Figure S9.  This figure depicts the distribution of mutations and mutation types across the EIF2B1 significant gene.

IL32

Figure S10.  This figure depicts the distribution of mutations and mutation types across the IL32 significant gene.

OR51S1

Figure S11.  This figure depicts the distribution of mutations and mutation types across the OR51S1 significant gene.

LCE1B

Figure S12.  This figure depicts the distribution of mutations and mutation types across the LCE1B significant gene.

MS4A2

Figure S13.  This figure depicts the distribution of mutations and mutation types across the MS4A2 significant gene.

LRTM1

Figure S14.  This figure depicts the distribution of mutations and mutation types across the LRTM1 significant gene.

TCEB3C

Figure S15.  This figure depicts the distribution of mutations and mutation types across the TCEB3C significant gene.

DNAH7

Figure S16.  This figure depicts the distribution of mutations and mutation types across the DNAH7 significant gene.

GPR141

Figure S17.  This figure depicts the distribution of mutations and mutation types across the GPR141 significant gene.

SCN5A

Figure S18.  This figure depicts the distribution of mutations and mutation types across the SCN5A significant gene.

LRRC4C

Figure S19.  This figure depicts the distribution of mutations and mutation types across the LRRC4C significant gene.

KIAA2022

Figure S20.  This figure depicts the distribution of mutations and mutation types across the KIAA2022 significant gene.

TCHHL1

Figure S21.  This figure depicts the distribution of mutations and mutation types across the TCHHL1 significant gene.

TUBAL3

Figure S22.  This figure depicts the distribution of mutations and mutation types across the TUBAL3 significant gene.

MPP7

Figure S23.  This figure depicts the distribution of mutations and mutation types across the MPP7 significant gene.

C1QTNF9

Figure S24.  This figure depicts the distribution of mutations and mutation types across the C1QTNF9 significant gene.

KCNB2

Figure S25.  This figure depicts the distribution of mutations and mutation types across the KCNB2 significant gene.

B2M

Figure S26.  This figure depicts the distribution of mutations and mutation types across the B2M significant gene.

FAM113B

Figure S27.  This figure depicts the distribution of mutations and mutation types across the FAM113B significant gene.

PROL1

Figure S28.  This figure depicts the distribution of mutations and mutation types across the PROL1 significant gene.

C18orf26

Figure S29.  This figure depicts the distribution of mutations and mutation types across the C18orf26 significant gene.

NF1

Figure S30.  This figure depicts the distribution of mutations and mutation types across the NF1 significant gene.

GK2

Figure S31.  This figure depicts the distribution of mutations and mutation types across the GK2 significant gene.

OR4E2

Figure S32.  This figure depicts the distribution of mutations and mutation types across the OR4E2 significant gene.

SV2B

Figure S33.  This figure depicts the distribution of mutations and mutation types across the SV2B significant gene.

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)
Copyright © 2013 Broad Institute TCGA GDAC as part of the TCGA Research Network. All rights reserved.
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