Skin Cutaneous Melanoma: Mutation Analysis (MutSigCV v0.9)
(Regional_LN 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_LN

  • Number of patients in set: 105

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_LN.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: 7. 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 48405 12810 738 29 29 5 0 0 20 0.66 4.1e-15 87 0.099 6.4e-11
BRAF 181335 51765 3051 64 59 14 3 0 19 0.69 7e-15 140 0.1 6.4e-11
CDKN2A 63210 17955 558 16 16 12 1 0 6 0.53 8.8e-12 69 0.1 5.3e-08
PTEN 102270 24570 1566 11 11 11 0 0 20 0.61 4.9e-09 48 0.098 0.000022
C18orf26 51765 15330 576 15 13 14 4 0 20 1.3 2.4e-06 36 0.1 0.0087
PPIAL4G 40950 10920 216 8 8 6 3 0 20 0.64 2e-05 25 0.094 0.06
TCEB3C 80220 25830 99 17 14 13 4 0 20 1.5 0.000027 38 0.097 0.071
TP53 99225 28980 1854 20 18 18 1 0 4 1.3 0.000052 52 0.1 0.12
PPP6C 77490 21210 1179 11 10 9 0 0 20 0.68 0.000059 29 0.095 0.12
B2M 30135 8400 576 4 4 3 0 0 20 0.83 0.000069 22 0.093 0.12
CCNE2 115080 28665 2196 10 10 7 0 0 20 0.58 0.000075 29 0.1 0.12
TUBAL3 109410 32340 747 8 7 8 1 0 20 0.2 0.00015 19 0.095 0.22
IL32 42840 11235 981 4 4 2 2 0 20 1 0.0003 23 0.19 0.42
GPR141 74970 21210 216 8 8 6 1 0 20 0.47 0.00041 23 0.098 0.5
GALNTL5 112770 29610 1467 13 10 12 2 0 20 0.67 0.00046 28 0.11 0.5
AOAH 153405 36750 3672 10 9 9 5 0 20 0.5 0.00048 29 0.095 0.5
SLC10A2 85995 25620 1107 14 12 11 4 0 18 1.2 0.00049 26 0.095 0.5
EIF2B1 88095 25200 1953 5 5 2 0 0 20 0.5 0.00049 25 0.1 0.5
DSG1 260190 74970 2700 32 18 32 6 0 20 0.71 0.00055 39 0.1 0.52
KCNB2 223125 63945 396 37 25 32 16 0 20 2.1 0.00057 47 0.1 0.52
PSCA 14070 4410 72 2 2 2 0 0 20 0.5 0.00067 13 0.084 0.58
OR4E2 75285 22995 234 13 12 9 10 0 20 0.98 0.00081 24 0.095 0.65
DNAJC5B 50190 13230 720 7 7 7 1 0 20 0.5 0.00082 19 0.094 0.65
SERPINB11 88620 23835 873 14 12 13 3 0 20 1.1 0.0011 26 0.095 0.87
TMPRSS11B 105630 27510 1782 13 10 13 5 0 11 1.4 0.0013 31 0.1 0.89
NEUROD4 81270 23205 198 15 9 15 4 0 20 0.67 0.0013 22 0.094 0.89
EPB42 177555 53445 2340 12 8 12 4 0 20 0.38 0.0014 29 0.11 0.93
GCOM1 198660 50925 2673 18 14 18 6 0 18 0.52 0.0016 30 0.1 1
SV2B 173250 46200 2178 20 16 19 6 0 20 1 0.0016 32 0.097 1
SERPINB10 99960 25200 1251 7 7 6 3 0 20 0.61 0.0017 22 0.094 1
OR52L1 76335 25095 135 12 12 10 3 0 20 1.4 0.0021 25 0.095 1
ZG16B 46095 13965 612 6 6 6 3 0 20 0.74 0.0022 17 0.093 1
VEGFC 100695 25935 1161 13 12 12 1 0 6 1.2 0.0023 30 0.098 1
TRERF1 282870 83895 2367 25 18 22 5 0 11 0.64 0.0025 43 0.11 1
KIAA2022 372120 99435 468 32 25 29 14 0 11 1 0.0026 49 0.1 1
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.

C18orf26

Figure S5.  This figure depicts the distribution of mutations and mutation types across the C18orf26 significant gene.

PPIAL4G

Figure S6.  This figure depicts the distribution of mutations and mutation types across the PPIAL4G significant gene.

TCEB3C

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