Skin Cutaneous Melanoma: Mutation Analysis (MutSigCV v0.9)
(All_Samples 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_Samples

  • Number of patients in set: 264

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_Samples.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: 55. 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
BRAF 455928 130152 9492 147 140 18 3 0 19 0.76 0 370 0.25 0
CDKN2A 158928 45144 1736 34 34 16 1 0 6 0.57 1.9e-15 150 0.34 1.7e-11
NRAS 121704 32208 2296 73 73 9 1 0 20 0.75 3e-15 230 0.26 1.8e-11
TP53 249480 72864 5768 43 39 34 1 0 4 0.92 6.9e-15 130 0.25 3.1e-11
PTEN 257136 61776 4872 23 23 20 0 0 20 0.55 1.2e-14 110 0.26 4.4e-11
PPP6C 194832 53328 3668 24 23 15 2 0 20 0.66 2.2e-12 74 0.33 6.5e-09
DSG1 654192 188496 8400 61 43 53 14 0 20 0.67 4.4e-09 90 0.25 0.000012
IL32 107712 28248 3052 10 10 6 3 0 20 0.89 3.8e-07 46 0.28 0.00087
TCEB3C 201696 64944 308 34 29 24 11 0 20 1.5 8e-07 68 0.27 0.0016
PPIAL4G 102960 27456 672 12 12 9 7 0 20 0.66 1.9e-06 38 0.26 0.0035
OR51S1 190344 64944 756 35 30 24 10 0 20 1.7 4e-06 60 0.27 0.0065
TCHHL1 561000 155496 1232 52 37 50 9 0 17 0.62 4.2e-06 66 0.26 0.0065
DNAH7 2557368 674784 35252 183 92 163 68 0 20 1.6 5.6e-06 160 0.25 0.0078
LRTM1 210144 63624 1764 30 25 29 14 0 20 1.1 7e-06 52 0.26 0.0091
TUBAL3 275088 81312 2324 13 12 13 5 0 20 0.2 9.7e-06 32 0.24 0.011
AOAH 385704 92400 11424 23 22 21 9 0 20 0.72 9.9e-06 56 0.24 0.011
EIF2B1 221496 63360 6076 9 9 3 3 0 20 0.56 1e-05 44 0.24 0.011
NF1 2484768 696432 33152 52 38 48 9 0 0 0.34 0.000012 130 0.28 0.013
LCE1B 73128 21120 672 12 12 12 1 0 20 1.2 0.000015 35 0.25 0.014
MPP7 369864 97152 8820 35 29 30 6 0 8 0.95 0.000019 63 0.26 0.017
B2M 75768 21120 1792 6 6 5 0 0 20 0.89 2e-05 32 0.24 0.017
MS4A2 156288 45408 3668 10 10 10 1 0 11 0.27 0.000022 32 0.27 0.018
OR4E2 189288 57816 728 24 23 17 16 0 20 1.2 0.000025 47 0.28 0.02
SCN5A 1168728 341352 10052 88 60 84 48 0 20 1.1 0.000026 110 0.28 0.02
TPTE2 338184 87912 14532 38 32 32 7 1 14 1.4 3e-05 68 0.25 0.022
FAM113B 227040 72864 504 23 22 19 18 0 20 0.82 0.000034 49 0.25 0.023
OR4K1 192192 54384 672 32 29 24 23 0 20 2.2 0.000034 58 0.29 0.023
RBM11 136224 36432 1260 16 16 14 0 0 20 1.4 0.000036 44 0.32 0.024
TSHB 87648 23760 1176 7 6 6 2 0 20 0.18 5e-05 18 0.22 0.031
OR2W1 195096 56232 616 22 21 16 10 0 20 1.6 0.000054 49 0.26 0.032
KCNB2 561000 160776 1232 74 57 59 34 0 20 2.1 0.000054 92 0.27 0.032
GPR141 188496 53328 672 14 14 10 6 0 20 0.59 0.000056 37 0.24 0.032
C1QTNF9 172920 52272 1764 15 15 13 3 0 19 0.62 0.000059 38 0.24 0.033
SLC15A2 467808 130944 12376 38 30 32 14 0 20 0.91 0.000073 64 0.27 0.039
CCNE2 289344 72072 6832 14 13 10 2 0 20 0.56 0.000091 39 0.32 0.046
BRAF

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

CDKN2A

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

NRAS

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

TP53

Figure S4.  This figure depicts the distribution of mutations and mutation types across the TP53 significant gene.

PTEN

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

PPP6C

Figure S6.  This figure depicts the distribution of mutations and mutation types across the PPP6C significant gene.

DSG1

Figure S7.  This figure depicts the distribution of mutations and mutation types across the DSG1 significant gene.

IL32

Figure S8.  This figure depicts the distribution of mutations and mutation types across the IL32 significant gene.

TCEB3C

Figure S9.  This figure depicts the distribution of mutations and mutation types across the TCEB3C significant gene.

PPIAL4G

Figure S10.  This figure depicts the distribution of mutations and mutation types across the PPIAL4G significant gene.

OR51S1

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

TCHHL1

Figure S12.  This figure depicts the distribution of mutations and mutation types across the TCHHL1 significant gene.

DNAH7

Figure S13.  This figure depicts the distribution of mutations and mutation types across the DNAH7 significant gene.

LRTM1

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

TUBAL3

Figure S15.  This figure depicts the distribution of mutations and mutation types across the TUBAL3 significant gene.

EIF2B1

Figure S16.  This figure depicts the distribution of mutations and mutation types across the EIF2B1 significant gene.

NF1

Figure S17.  This figure depicts the distribution of mutations and mutation types across the NF1 significant gene.

LCE1B

Figure S18.  This figure depicts the distribution of mutations and mutation types across the LCE1B significant gene.

MPP7

Figure S19.  This figure depicts the distribution of mutations and mutation types across the MPP7 significant gene.

B2M

Figure S20.  This figure depicts the distribution of mutations and mutation types across the B2M significant gene.

MS4A2

Figure S21.  This figure depicts the distribution of mutations and mutation types across the MS4A2 significant gene.

OR4E2

Figure S22.  This figure depicts the distribution of mutations and mutation types across the OR4E2 significant gene.

SCN5A

Figure S23.  This figure depicts the distribution of mutations and mutation types across the SCN5A significant gene.

TPTE2

Figure S24.  This figure depicts the distribution of mutations and mutation types across the TPTE2 significant gene.

FAM113B

Figure S25.  This figure depicts the distribution of mutations and mutation types across the FAM113B significant gene.

OR4K1

Figure S26.  This figure depicts the distribution of mutations and mutation types across the OR4K1 significant gene.

RBM11

Figure S27.  This figure depicts the distribution of mutations and mutation types across the RBM11 significant gene.

TSHB

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

OR2W1

Figure S29.  This figure depicts the distribution of mutations and mutation types across the OR2W1 significant gene.

KCNB2

Figure S30.  This figure depicts the distribution of mutations and mutation types across the KCNB2 significant gene.

GPR141

Figure S31.  This figure depicts the distribution of mutations and mutation types across the GPR141 significant gene.

C1QTNF9

Figure S32.  This figure depicts the distribution of mutations and mutation types across the C1QTNF9 significant gene.

SLC15A2

Figure S33.  This figure depicts the distribution of mutations and mutation types across the SLC15A2 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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