Mutation Analysis (MutSigCV v0.9)
Stomach and Esophageal carcinoma (Primary solid tumor)
28 January 2016  |  analyses__2016_01_28
Maintainer Information
Citation Information
doi:10.7908/C1PG1R7Q
Maintained by David Heiman (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2016): Mutation Analysis (MutSigCV v0.9). Broad Institute of MIT and Harvard. doi:10.7908/C1PG1R7Q
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: STES-TP

  • Number of patients in set: 580

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

  • MAF used for this analysis:STES-TP.final_analysis_set.maf

  • Blacklist used for this analysis: pancan_mutation_blacklist.v14.hg19.txt

  • Significantly mutated genes (q ≤ 0.1): 687

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). If the figure is unpopulated, then full coverage is assumed (e.g. MutSig CV doesn't use WIGs and assumes full coverage).

Figure 1. 

Distribution of Mutation Counts, Coverage, and Mutation Rates Across Samples

Figure 2.  Patients counts and rates file used to generate this plot: STES-TP.patients.counts_and_rates.txt

Lego Plots

The mutation spectrum is depicted in the lego plots below in which the 96 possible mutation types are subdivided into six large blocks, color-coded to reflect the base substitution type. Each large block is further subdivided into the 16 possible pairs of 5' and 3' neighbors, as listed in the 4x4 trinucleotide context legend. The height of each block corresponds to the mutation frequency for that kind of mutation (counts of mutations normalized by the base coverage in a given bin). The shape of the spectrum is a signature for dominant mutational mechanisms in different tumor types.

Figure 3.  Get High-res Image SNV Mutation rate lego plot for entire set. Each bin is normalized by base coverage for that bin. Colors represent the six SNV types on the upper right. The three-base context for each mutation is labeled in the 4x4 legend on the lower right. The fractional breakdown of SNV counts is shown in the pie chart on the upper left. If this figure is blank, not enough information was provided in the MAF to generate it.

Figure 4.  Get High-res Image SNV Mutation rate lego plots for 4 slices of mutation allele fraction (0<=AF<0.1, 0.1<=AF<0.25, 0.25<=AF<0.5, & 0.5<=AF) . The color code and three-base context legends are the same as the previous figure. If this figure is blank, not enough information was provided in the MAF to generate it.

CoMut Plot

Figure 5.  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: 687. 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
ARID1A 2590860 763280 213568 139 114 111 1 0 2 0.33 0 520 0.49 0
TP53 548100 160080 117008 379 343 176 3 1 4 1.1 0 1300 0.49 0
MUC6 2329860 818960 150520 72 59 66 15 0 20 1.1 4.4e-16 210 0.46 2.7e-12
CSMD1 3917900 1118820 442472 148 111 136 8 3 2 0.9 1.8e-15 260 0.46 6.4e-12
B2M 166460 46400 36352 32 20 22 1 1 20 0.83 2.1e-15 99 0.45 6.4e-12
XYLT2 997020 308560 99968 47 40 17 5 0 16 0.69 2.1e-15 170 0.45 6.4e-12
CDKN2A 349160 99180 35216 37 35 32 7 7 6 2.1 4.1e-15 140 0.45 1.1e-11
GNG12 102080 27260 24992 12 12 4 2 0 20 0.69 4.7e-15 65 0.44 1.1e-11
JARID2 1630960 473860 235152 53 45 42 10 0 16 0.61 6.6e-15 150 0.45 1.1e-11
PIK3CA 1507420 385700 224928 101 84 42 2 0 20 1 7e-15 210 0.45 1.1e-11
RNF43 965700 305660 99400 65 47 27 5 4 8 0.95 7.3e-15 210 0.45 1.1e-11
SMAD4 767920 214020 126096 46 41 36 2 2 20 1 7.4e-15 140 0.45 1.1e-11
PTEN 564920 135720 98832 47 37 33 4 1 20 0.82 8.5e-15 170 0.45 1.1e-11
DCDC1 505760 137460 85768 52 46 52 6 4 20 1.8 8.9e-15 160 0.48 1.1e-11
LARP4B 991220 291160 186872 38 34 16 3 0 2 0.32 9.5e-15 150 0.47 1.1e-11
FBXW7 1126360 309140 135752 46 44 30 1 2 20 0.84 9.9e-15 150 0.46 1.1e-11
OR5M3 411220 116580 14200 26 25 16 1 0 20 0.8 1e-14 96 0.46 1.1e-11
CBWD1 439640 115420 120984 23 22 4 2 4 5 0.81 1.4e-14 110 0.45 1.5e-11
PGM5 621180 183860 102240 46 43 12 3 1 20 0.96 6.5e-14 110 0.45 6.2e-11
DST 9114120 2351900 4215696 135 95 131 31 0 0 0.45 8e-14 240 0.5 7.3e-11
TGFBR2 788800 211700 136320 32 31 26 3 1 20 1.1 3.9e-13 120 0.45 3.4e-10
CDH1 1133320 336980 196528 34 33 30 3 1 20 0.62 5.3e-13 120 0.44 4.4e-10
DDX59 854920 236060 80656 29 27 9 2 0 20 1.1 1.2e-12 120 0.46 9.1e-10
ZFP36L2 293480 94540 9088 15 15 13 1 0 20 0.57 1.3e-12 79 0.45 1e-09
PLEKHA6 1175660 341620 191416 35 28 22 6 0 20 0.57 1.6e-12 120 0.45 1.1e-09
KRAS 350900 85840 60208 40 40 6 0 0 1 0.27 2.4e-12 110 0.45 1.7e-09
WASF3 683820 204740 192552 25 22 16 7 1 13 0.59 3.9e-12 95 0.45 2.7e-09
KLF3 473860 136300 59072 25 22 17 4 0 7 0.83 6e-12 97 0.45 3.9e-09
LRRN2 915240 316680 11360 40 37 18 10 0 20 0.68 1.1e-11 110 0.45 7.2e-09
RHOA 385120 111940 63048 23 22 17 0 0 20 0.65 1.6e-11 77 0.44 1e-08
HLA-B 430360 131660 64752 38 35 33 0 0 1 1.5 2.2e-11 140 0.46 1.3e-08
MAP2K7 385120 106720 112464 40 27 38 0 3 20 1.1 2.9e-11 91 0.46 1.7e-08
FLG 5329040 1581660 24992 164 117 154 43 3 15 1.1 3e-11 240 0.47 1.7e-08
CTNND1 1265560 370040 185736 35 33 32 1 0 2 0.24 4e-11 140 0.48 2.1e-08
ERBB4 1828160 497640 414072 76 66 65 5 1 4 1.1 6.8e-11 170 0.46 3.6e-08
ARID1A

Figure S1.  This figure depicts the distribution of mutations and mutation types across the ARID1A significant gene.

TP53

Figure S2.  This figure depicts the distribution of mutations and mutation types across the TP53 significant gene.

MUC6

Figure S3.  This figure depicts the distribution of mutations and mutation types across the MUC6 significant gene.

CSMD1

Figure S4.  This figure depicts the distribution of mutations and mutation types across the CSMD1 significant gene.

B2M

Figure S5.  This figure depicts the distribution of mutations and mutation types across the B2M significant gene.

XYLT2

Figure S6.  This figure depicts the distribution of mutations and mutation types across the XYLT2 significant gene.

CDKN2A

Figure S7.  This figure depicts the distribution of mutations and mutation types across the CDKN2A significant gene.

GNG12

Figure S8.  This figure depicts the distribution of mutations and mutation types across the GNG12 significant gene.

JARID2

Figure S9.  This figure depicts the distribution of mutations and mutation types across the JARID2 significant gene.

PIK3CA

Figure S10.  This figure depicts the distribution of mutations and mutation types across the PIK3CA significant gene.

RNF43

Figure S11.  This figure depicts the distribution of mutations and mutation types across the RNF43 significant gene.

SMAD4

Figure S12.  This figure depicts the distribution of mutations and mutation types across the SMAD4 significant gene.

PTEN

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

DCDC1

Figure S14.  This figure depicts the distribution of mutations and mutation types across the DCDC1 significant gene.

LARP4B

Figure S15.  This figure depicts the distribution of mutations and mutation types across the LARP4B significant gene.

FBXW7

Figure S16.  This figure depicts the distribution of mutations and mutation types across the FBXW7 significant gene.

OR5M3

Figure S17.  This figure depicts the distribution of mutations and mutation types across the OR5M3 significant gene.

CBWD1

Figure S18.  This figure depicts the distribution of mutations and mutation types across the CBWD1 significant gene.

PGM5

Figure S19.  This figure depicts the distribution of mutations and mutation types across the PGM5 significant gene.

TGFBR2

Figure S20.  This figure depicts the distribution of mutations and mutation types across the TGFBR2 significant gene.

CDH1

Figure S21.  This figure depicts the distribution of mutations and mutation types across the CDH1 significant gene.

DDX59

Figure S22.  This figure depicts the distribution of mutations and mutation types across the DDX59 significant gene.

ZFP36L2

Figure S23.  This figure depicts the distribution of mutations and mutation types across the ZFP36L2 significant gene.

PLEKHA6

Figure S24.  This figure depicts the distribution of mutations and mutation types across the PLEKHA6 significant gene.

KRAS

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

WASF3

Figure S26.  This figure depicts the distribution of mutations and mutation types across the WASF3 significant gene.

KLF3

Figure S27.  This figure depicts the distribution of mutations and mutation types across the KLF3 significant gene.

LRRN2

Figure S28.  This figure depicts the distribution of mutations and mutation types across the LRRN2 significant gene.

RHOA

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

HLA-B

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

MAP2K7

Figure S31.  This figure depicts the distribution of mutations and mutation types across the MAP2K7 significant gene.

FLG

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

CTNND1

Figure S33.  This figure depicts the distribution of mutations and mutation types across the CTNND1 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

In addition to the links below, the full results of the analysis summarized in this report can also be downloaded programmatically using firehose_get, or interactively from either the Broad GDAC website or TCGA Data Coordination Center Portal.

References
[1] TCGA, Integrated genomic analyses of ovarian carcinoma, Nature 474:609 - 615 (2011)
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