Skin Cutaneous Melanoma: Mutation Analysis (MutSigCV v0.9)
(Regional_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-Regional_Metastatic

  • Number of patients in set: 137

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-Regional_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: 10. 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 63157 16714 820 39 39 6 0 0 20 0.7 2.7e-15 120 0.1 4.9e-11
BRAF 236599 67541 3390 78 73 16 3 0 19 0.76 6e-15 180 0.096 5.5e-11
CDKN2A 82474 23427 620 23 23 13 1 0 6 0.62 9.1e-15 110 0.097 5.5e-11
PTEN 133438 32058 1740 12 12 12 0 0 20 0.58 6.8e-10 55 0.095 3.1e-06
PPP6C 101106 27674 1310 15 14 11 1 0 20 0.68 3e-07 42 0.093 0.0011
TP53 129465 37812 2060 26 23 23 1 0 4 1.2 1.5e-06 66 0.096 0.0044
TCEB3C 104668 33702 110 23 19 17 7 0 20 1.5 6.8e-06 46 0.095 0.018
C18orf26 67541 20002 640 15 13 14 5 0 20 1.3 8.1e-06 37 0.093 0.018
PPIAL4G 53430 14248 240 9 9 6 4 0 20 0.67 0.000011 28 0.09 0.023
GPR141 97818 27674 240 12 12 9 2 0 20 0.52 0.000019 32 0.095 0.034
DSG1 339486 97818 3000 38 24 37 8 0 20 0.73 0.000077 49 0.14 0.13
DDX3X 217145 57814 3240 14 14 14 0 0 12 1 0.0001 49 0.096 0.15
KCNB2 291125 83433 440 49 34 41 20 0 20 2 0.00011 59 0.095 0.16
EIF2B1 114943 32880 2170 6 6 2 1 0 20 0.56 0.00012 31 0.096 0.16
B2M 39319 10960 640 4 4 3 0 0 20 0.79 0.00014 22 0.088 0.16
SV2B 226050 60280 2420 23 19 22 6 0 20 0.99 0.00014 43 0.094 0.16
CCNE2 150152 37401 2440 10 10 7 0 0 20 0.64 0.00029 30 0.093 0.31
IL32 55896 14659 1090 5 5 3 2 0 20 0.96 0.00031 25 0.094 0.31
TUBAL3 142754 42196 830 8 7 8 3 0 20 0.2 0.0004 19 0.088 0.39
GCOM1 259204 66445 2970 21 17 20 7 0 18 0.49 0.00048 36 0.1 0.44
SLC9A11 373873 95215 5230 37 25 32 7 0 20 0.93 0.00061 47 0.095 0.53
GZMA 85488 24523 1030 10 9 9 2 0 20 0.62 0.00066 24 0.092 0.55
KIAA2022 485528 129739 520 39 29 34 18 0 11 1.1 0.00075 62 0.1 0.55
SGCZ 97681 29044 2330 17 16 16 6 0 16 1.8 0.00077 34 0.094 0.55
AOAH 200157 47950 4080 11 10 10 5 0 20 0.53 0.00078 31 0.092 0.55
MPP7 191937 50416 3150 21 16 20 3 0 8 0.87 0.00079 38 0.095 0.55
IL1F8 78912 20413 1250 10 10 8 4 0 19 1.5 0.00095 28 0.094 0.64
ADH1C 121793 36305 1460 22 20 18 4 0 20 1.6 0.0012 35 0.092 0.75
PSCA 18358 5754 80 2 2 2 0 0 20 0.55 0.0012 14 0.08 0.75
OR4E2 98229 30003 260 14 13 9 11 0 20 0.97 0.0014 26 0.093 0.81
TIMD4 121793 37401 1800 13 8 13 4 0 20 0.62 0.0014 27 0.092 0.81
SERPINB11 115628 31099 970 16 14 15 4 0 20 1.3 0.0015 30 0.093 0.83
GALNTL5 147138 38634 1630 13 10 12 2 0 20 0.69 0.0015 28 0.094 0.83
DNAJC5B 65486 17262 800 7 7 7 1 0 20 0.49 0.0016 19 0.091 0.83
CD2 114395 31510 1020 20 14 17 4 0 11 1.2 0.0016 32 0.094 0.83
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.

CDKN2A

Figure S3.  This figure depicts the distribution of mutations and mutation types across the CDKN2A significant gene.

PTEN

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

PPP6C

Figure S5.  This figure depicts the distribution of mutations and mutation types across the PPP6C significant gene.

TP53

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

TCEB3C

Figure S7.  This figure depicts the distribution of mutations and mutation types across the TCEB3C significant gene.

C18orf26

Figure S8.  This figure depicts the distribution of mutations and mutation types across the C18orf26 significant gene.

PPIAL4G

Figure S9.  This figure depicts the distribution of mutations and mutation types across the PPIAL4G significant gene.

GPR141

Figure S10.  This figure depicts the distribution of mutations and mutation types across the GPR141 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)
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