Mutation Analysis (MutSigCV v0.9)
Uterine Corpus Endometrioid Carcinoma (Primary solid tumor)
28 January 2016  |  analyses__2016_01_28
Maintainer Information
Citation Information
doi:10.7908/C17H1J46
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/C17H1J46
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: UCEC-TP

  • Number of patients in set: 248

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:UCEC-TP.final_analysis_set.maf

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

  • Significantly mutated genes (q ≤ 0.1): 70

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: UCEC-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: 70. 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
CTNNB1 456072 136400 69372 80 74 25 7 1 20 1.6 0 190 0.3 0
PIK3CA 644552 164920 97416 172 132 76 3 0 20 1.2 3.3e-16 380 0.27 3e-12
PTEN 241552 58032 42804 254 161 149 5 0 20 0.94 1.1e-15 780 0.27 6.8e-12
TP53 234360 68448 50676 74 69 50 2 0 4 0.76 4e-15 230 0.28 1.4e-11
FBXW7 481616 132184 58794 45 38 29 1 2 20 1.2 4.4e-15 110 0.29 1.4e-11
ARID1A 1107816 326368 92496 107 83 87 5 0 2 0.55 5.1e-15 400 0.29 1.4e-11
KRAS 150040 36704 26076 52 52 11 1 1 1 2 6.3e-15 120 0.25 1.4e-11
PIK3R1 462272 118792 84870 117 82 88 1 2 20 1.3 6.7e-15 410 0.25 1.4e-11
CTCF 437472 112096 49446 50 44 39 1 0 20 0.62 7.1e-15 200 0.34 1.4e-11
ARID5B 692912 194432 47478 34 29 33 8 1 20 1.5 1e-12 100 0.25 1.9e-09
FGFR2 518320 145080 126198 34 31 19 3 1 18 1.1 6.1e-12 87 0.29 1e-08
SPOP 226920 59520 45264 23 21 18 0 0 20 1 2.2e-11 66 0.46 3.4e-08
PPP2R1A 328104 102672 68142 31 28 19 2 0 17 1.4 3.7e-09 72 0.28 5.2e-06
MORC4 534936 136896 75522 27 20 25 3 0 15 0.92 5.2e-09 70 0.25 6.8e-06
CHD4 1150472 307024 230748 44 35 39 2 2 20 0.67 7.5e-09 83 0.25 9.1e-06
FAM9A 154008 38192 32964 21 14 20 1 0 14 1.5 1.9e-07 49 0.38 0.00022
FOXA2 199392 55056 7872 12 12 12 1 0 20 1.7 2.5e-07 56 0.35 0.00027
CASP8 361088 84568 52398 21 17 19 5 1 20 1.2 3.4e-07 56 0.24 0.00035
CCND1 145328 41664 17958 14 14 12 1 0 20 1.6 1.1e-06 46 0.3 0.001
SIN3A 754912 208320 98400 29 21 27 3 0 20 0.99 2.4e-06 67 0.3 0.0022
BRS3 229400 69440 15498 17 15 17 2 0 20 0.93 2.8e-06 41 0.26 0.0023
DCDC1 216256 58776 37146 26 16 25 4 1 20 1.5 2.8e-06 44 0.27 0.0023
RB1 706304 186248 119556 29 20 27 4 0 20 0.83 5.2e-06 57 0.81 0.0041
DNER 377952 102920 56088 21 18 20 0 0 20 0.87 7.8e-06 48 0.31 0.0059
RNF43 412920 130696 43050 14 12 14 3 0 8 0.67 8.7e-06 46 0.4 0.0063
CHIC1 31744 7936 8118 4 4 4 0 0 20 0.75 0.000011 21 0.41 0.0077
ATF6 398288 113832 78228 19 14 17 4 0 20 0.94 0.000013 48 0.33 0.0088
ATP11C 680760 182776 172446 38 20 35 14 1 20 1.2 0.000014 61 0.27 0.0088
SYCP1 536424 125488 122754 22 16 22 2 0 6 0.93 0.000014 56 0.42 0.0089
BCOR 883872 264368 50430 43 30 34 19 0 20 1 3e-05 65 0.25 0.018
CNPY1 57288 13392 15252 8 7 7 0 0 19 1.2 0.000031 25 0.43 0.018
NFE2L3 310248 81840 15990 13 12 13 2 0 20 1.1 0.000032 42 0.23 0.018
PPIG 456568 106144 59286 23 16 23 5 0 20 0.91 0.000038 47 0.27 0.021
RUNDC3B 268088 71424 54612 14 11 12 0 0 7 0.69 0.000039 40 0.25 0.021
NAA15 516336 124000 90528 16 14 16 3 0 20 1.1 4e-05 50 0.48 0.021
CTNNB1

Figure S1.  This figure depicts the distribution of mutations and mutation types across the CTNNB1 significant gene.

PIK3CA

Figure S2.  This figure depicts the distribution of mutations and mutation types across the PIK3CA significant gene.

PTEN

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

TP53

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

FBXW7

Figure S5.  This figure depicts the distribution of mutations and mutation types across the FBXW7 significant gene.

ARID1A

Figure S6.  This figure depicts the distribution of mutations and mutation types across the ARID1A significant gene.

KRAS

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

PIK3R1

Figure S8.  This figure depicts the distribution of mutations and mutation types across the PIK3R1 significant gene.

CTCF

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

ARID5B

Figure S10.  This figure depicts the distribution of mutations and mutation types across the ARID5B significant gene.

FGFR2

Figure S11.  This figure depicts the distribution of mutations and mutation types across the FGFR2 significant gene.

SPOP

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

PPP2R1A

Figure S13.  This figure depicts the distribution of mutations and mutation types across the PPP2R1A significant gene.

MORC4

Figure S14.  This figure depicts the distribution of mutations and mutation types across the MORC4 significant gene.

CHD4

Figure S15.  This figure depicts the distribution of mutations and mutation types across the CHD4 significant gene.

FAM9A

Figure S16.  This figure depicts the distribution of mutations and mutation types across the FAM9A significant gene.

FOXA2

Figure S17.  This figure depicts the distribution of mutations and mutation types across the FOXA2 significant gene.

CCND1

Figure S18.  This figure depicts the distribution of mutations and mutation types across the CCND1 significant gene.

BRS3

Figure S19.  This figure depicts the distribution of mutations and mutation types across the BRS3 significant gene.

DCDC1

Figure S20.  This figure depicts the distribution of mutations and mutation types across the DCDC1 significant gene.

RB1

Figure S21.  This figure depicts the distribution of mutations and mutation types across the RB1 significant gene.

DNER

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

RNF43

Figure S23.  This figure depicts the distribution of mutations and mutation types across the RNF43 significant gene.

CHIC1

Figure S24.  This figure depicts the distribution of mutations and mutation types across the CHIC1 significant gene.

ATP11C

Figure S25.  This figure depicts the distribution of mutations and mutation types across the ATP11C significant gene.

SYCP1

Figure S26.  This figure depicts the distribution of mutations and mutation types across the SYCP1 significant gene.

BCOR

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

CNPY1

Figure S28.  This figure depicts the distribution of mutations and mutation types across the CNPY1 significant gene.

NFE2L3

Figure S29.  This figure depicts the distribution of mutations and mutation types across the NFE2L3 significant gene.

PPIG

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

RUNDC3B

Figure S31.  This figure depicts the distribution of mutations and mutation types across the RUNDC3B 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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