Skin Cutaneous Melanoma: Mutation Analysis (MutSigCV v0.9)
(metastatic tumor 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-TM

  • Number of patients in set: 225

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-TM.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: 31. 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 388575 110925 7119 120 115 16 2 0 19 0.77 0 300 0.22 0
NRAS 103725 27450 1722 65 65 9 1 0 20 0.79 2.2e-15 200 0.22 2e-11
CDKN2A 135450 38475 1302 31 31 15 1 0 6 0.65 6.8e-15 140 0.23 4.1e-11
PTEN 219150 52650 3654 18 18 16 0 0 20 0.57 1.3e-14 86 0.21 5.7e-11
TP53 212625 62100 4326 37 34 31 1 0 4 0.97 9.5e-14 110 0.22 3.5e-10
PPP6C 166050 45450 2751 18 17 13 2 0 20 0.69 6.6e-09 57 0.21 2e-05
DSG1 557550 160650 6300 50 37 44 8 0 20 0.58 9.3e-09 79 0.22 0.000024
LCE1B 62325 18000 504 13 13 13 0 0 20 1.2 9.4e-07 38 0.21 0.0022
IL32 91800 24075 2289 9 9 6 2 0 20 0.96 5e-06 39 0.21 0.01
EIF2B1 188775 54000 4557 9 9 3 3 0 20 0.61 6.4e-06 43 0.22 0.012
OR51S1 162225 55350 567 27 26 18 6 0 20 1.6 7.6e-06 53 0.21 0.012
TCEB3C 171900 55350 231 31 26 23 9 0 20 1.5 8e-06 58 0.21 0.012
MS4A2 133200 38700 2751 9 9 9 1 0 11 0.24 0.000014 31 0.21 0.02
LRRC4C 332100 99450 504 37 32 32 14 0 13 1.5 0.000016 71 0.22 0.02
DNAH7 2179575 575100 26439 144 80 134 51 0 20 1.6 0.000016 140 0.22 0.02
PPIAL4G 87750 23400 504 11 11 8 7 0 20 0.78 0.000024 32 0.21 0.027
AOAH 328725 78750 8568 21 20 19 8 0 20 0.72 3e-05 50 0.21 0.033
KIAA2022 797400 213075 1092 56 43 50 18 0 11 0.93 0.000033 85 0.22 0.033
TCHHL1 478125 132525 924 40 30 38 6 0 17 0.61 0.000034 56 0.21 0.033
TSGA13 151875 38925 2961 10 9 8 2 0 18 0.44 0.000036 33 0.21 0.033
GPR141 160650 45450 504 13 13 9 5 0 20 0.61 0.000038 36 0.21 0.033
B2M 64575 18000 1344 5 5 4 0 0 20 0.86 0.000046 28 0.21 0.038
MPP7 315225 82800 6615 27 24 23 5 0 8 0.79 0.000058 53 0.22 0.043
CYP4Z1 266400 69075 4473 20 19 19 6 0 20 0.83 0.000061 46 0.21 0.043
GK2 288225 84825 483 33 28 28 5 0 20 1.6 0.000062 60 0.22 0.043
LRTM1 179100 54225 1323 23 22 22 10 0 20 1.1 0.000064 43 0.21 0.043
FAM113B 193500 62100 378 19 19 16 15 0 20 0.86 0.000064 44 0.21 0.043
SCN5A 996075 290925 7539 73 54 70 34 0 20 1 0.000068 94 0.22 0.044
RBM11 116100 31050 945 12 12 10 0 0 20 1.3 0.00011 38 0.21 0.068
AMHR2 284400 82800 4221 14 13 14 3 0 20 0.71 0.00017 46 0.21 0.1
PREX2 909900 236025 25956 70 55 63 24 0 12 1.3 0.00017 92 0.22 0.1
OR4E2 161325 49275 546 19 19 14 12 0 20 1.1 0.00018 38 0.21 0.1
CCNE2 246600 61425 5124 12 12 8 2 0 20 0.6 0.00019 36 0.21 0.11
OR2W1 166275 47925 462 17 16 13 5 0 20 1.4 0.0002 40 0.21 0.11
C1QTNF9 147375 44550 1323 13 13 12 3 0 19 0.68 0.00027 33 0.21 0.14
BRAF

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

NRAS

Figure S2.  This figure depicts the distribution of mutations and mutation types across the NRAS 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.

TP53

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

LCE1B

Figure S8.  This figure depicts the distribution of mutations and mutation types across the LCE1B significant gene.

IL32

Figure S9.  This figure depicts the distribution of mutations and mutation types across the IL32 significant gene.

EIF2B1

Figure S10.  This figure depicts the distribution of mutations and mutation types across the EIF2B1 significant gene.

OR51S1

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

TCEB3C

Figure S12.  This figure depicts the distribution of mutations and mutation types across the TCEB3C significant gene.

MS4A2

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

LRRC4C

Figure S14.  This figure depicts the distribution of mutations and mutation types across the LRRC4C significant gene.

DNAH7

Figure S15.  This figure depicts the distribution of mutations and mutation types across the DNAH7 significant gene.

PPIAL4G

Figure S16.  This figure depicts the distribution of mutations and mutation types across the PPIAL4G significant gene.

KIAA2022

Figure S17.  This figure depicts the distribution of mutations and mutation types across the KIAA2022 significant gene.

TCHHL1

Figure S18.  This figure depicts the distribution of mutations and mutation types across the TCHHL1 significant gene.

TSGA13

Figure S19.  This figure depicts the distribution of mutations and mutation types across the TSGA13 significant gene.

GPR141

Figure S20.  This figure depicts the distribution of mutations and mutation types across the GPR141 significant gene.

B2M

Figure S21.  This figure depicts the distribution of mutations and mutation types across the B2M significant gene.

MPP7

Figure S22.  This figure depicts the distribution of mutations and mutation types across the MPP7 significant gene.

CYP4Z1

Figure S23.  This figure depicts the distribution of mutations and mutation types across the CYP4Z1 significant gene.

GK2

Figure S24.  This figure depicts the distribution of mutations and mutation types across the GK2 significant gene.

LRTM1

Figure S25.  This figure depicts the distribution of mutations and mutation types across the LRTM1 significant gene.

FAM113B

Figure S26.  This figure depicts the distribution of mutations and mutation types across the FAM113B significant gene.

SCN5A

Figure S27.  This figure depicts the distribution of mutations and mutation types across the SCN5A significant gene.

RBM11

Figure S28.  This figure depicts the distribution of mutations and mutation types across the RBM11 significant gene.

AMHR2

Figure S29.  This figure depicts the distribution of mutations and mutation types across the AMHR2 significant gene.

PREX2

Figure S30.  This figure depicts the distribution of mutations and mutation types across the PREX2 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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