Mutation Analysis (MutSig 2CV v3.1)
Prostate Adenocarcinoma (Primary solid tumor)
02 April 2015  |  analyses__2015_04_02
Maintainer Information
Citation Information
doi:10.7908/C1MK6BZG
Maintained by David Heiman (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2015): Mutation Analysis (MutSig 2CV v3.1). Broad Institute of MIT and Harvard. doi:10.7908/C1MK6BZG
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. MutSig 2CV v3.1 was used to generate the results found in this report.

  • Working with individual set: PRAD-TP

  • Number of patients in set: 425

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:PRAD-TP.final_analysis_set.maf

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

  • Significantly mutated genes (q ≤ 0.1): 45

Results
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 1.  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 2.  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 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

  • 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: 45. 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).

rank gene longname codelen nnei nncd nsil nmis nstp nspl nind nnon npat nsite pCV pCL pFN p q
1 SPOP speckle-type POZ protein 1161 137 0 0 47 0 0 2 49 48 15 7.3e-16 1e-05 0.077 1e-16 9.1e-13
2 TP53 tumor protein p53 1889 141 0 0 31 0 4 9 44 43 34 3.8e-15 0.00047 1e-05 1e-16 9.1e-13
3 PTEN phosphatase and tensin homolog (mutated in multiple advanced cancers 1) 1244 60 0 0 4 1 1 8 14 14 14 4.9e-16 0.29 0.88 6.4e-15 3.9e-11
4 CTNNB1 catenin (cadherin-associated protein), beta 1, 88kDa 2406 175 0 0 11 0 0 0 11 11 8 3.5e-11 1e-05 0.018 1.3e-14 5.9e-11
5 FOXA1 forkhead box A1 1423 7 0 2 12 1 0 13 26 25 18 1.7e-08 1e-05 0.075 5.2e-12 1.9e-08
6 ATM ataxia telangiectasia mutated 9438 43 0 2 16 0 0 3 19 19 19 1.4e-10 1 0.01 1.1e-10 3.2e-07
7 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 3287 45 0 2 12 0 0 0 12 11 11 2.2e-06 0.0031 0.08 4.5e-08 0.00012
8 BRAF v-raf murine sarcoma viral oncogene homolog B1 2371 100 0 0 7 0 0 1 8 8 7 6.1e-06 0.039 0.022 2e-07 0.00046
9 HRAS v-Ha-ras Harvey rat sarcoma viral oncogene homolog 659 104 0 0 5 0 0 0 5 5 3 7.3e-06 0.0017 0.75 2.5e-07 0.00051
10 KDM6A lysine (K)-specific demethylase 6A 4318 5 0 1 2 1 2 4 9 9 9 1.2e-07 1 0.041 3e-07 0.00055
11 IDH1 isocitrate dehydrogenase 1 (NADP+), soluble 1277 543 0 0 5 0 0 0 5 5 2 0.00015 0.00013 0.88 3.7e-07 0.00061
12 SMG7 Smg-7 homolog, nonsense mediated mRNA decay factor (C. elegans) 3879 9 0 0 3 1 0 3 7 7 6 0.000011 0.018 0.084 4.3e-07 0.00062
13 ZMYM3 zinc finger, MYM-type 3 4227 7 0 0 4 1 1 4 10 9 10 2.8e-07 0.069 0.85 4.4e-07 0.00062
14 EHHADH enoyl-Coenzyme A, hydratase/3-hydroxyacyl Coenzyme A dehydrogenase 2198 31 0 0 4 0 0 1 5 5 5 1.5e-06 0.04 0.91 1.1e-06 0.0014
15 TP53BP1 tumor protein p53 binding protein 1 6042 23 0 0 3 2 0 3 8 7 8 2.6e-07 1 0.2 1.1e-06 0.0014
16 CNTNAP1 contactin associated protein 1 4779 143 0 2 6 0 0 1 7 7 5 0.0019 8e-05 0.85 3.4e-06 0.0039
17 BMP2K BMP2 inducible kinase 3582 45 0 0 4 1 0 1 6 6 5 1e-05 0.023 0.99 4.2e-06 0.0044
18 RPTN repetin 2363 19 0 1 3 1 0 2 6 6 5 3.1e-06 0.061 0.58 4.3e-06 0.0044
19 TCEB3 transcription elongation factor B (SIII), polypeptide 3 (110kDa, elongin A) 2439 28 0 0 1 1 1 1 4 4 4 4.9e-06 1 0.034 5.1e-06 0.0046
20 NTM neurotrimin 1195 41 0 0 4 0 2 0 6 6 6 0.000035 0.055 0.055 5.2e-06 0.0046
21 MED12 mediator complex subunit 12 6710 10 0 1 7 0 0 0 7 7 4 0.033 1e-05 0.23 5.3e-06 0.0046
22 MED15 mediator complex subunit 15 2437 22 0 0 3 0 1 2 6 6 6 1e-06 1 0.31 7.9e-06 0.0065
23 ERN1 endoplasmic reticulum to nucleus signaling 1 3018 37 0 0 0 0 0 3 3 3 2 0.000095 0.0068 0.41 1e-05 0.0077
24 LMOD2 leiomodin 2 (cardiac) 1652 49 0 0 2 0 0 3 5 5 3 0.0026 0.00053 0.089 1e-05 0.0077
25 FAM111A family with sequence similarity 111, member A 1848 15 0 1 1 0 0 2 3 3 2 0.00069 0.0051 0.1 0.000011 0.0077
26 ZNF709 zinc finger protein 709 1938 10 0 1 5 0 0 0 5 5 2 0.0044 0.00014 0.95 2e-05 0.014
27 MLLT10 myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated to, 10 3174 11 0 0 3 0 0 1 4 4 2 0.016 0.0001 0.31 0.000023 0.016
28 TNRC18 trinucleotide repeat containing 18 9019 0 0 0 4 0 0 3 7 6 6 0.00043 0.054 0.033 0.000024 0.016
29 GAGE2D G antigen 2D 1115 119 0 0 0 0 0 3 3 3 1 0.0021 0.001 0.73 3e-05 0.019
30 EMG1 EMG1 nucleolar protein homolog (S. cerevisiae) 1360 405 0 0 0 0 0 4 4 4 2 0.0065 0.0006 0.71 0.000052 0.032
31 LAMA3 laminin, alpha 3 10475 19 0 2 3 3 1 0 7 7 7 4.9e-06 1 0.43 0.000065 0.038
32 RPL11 ribosomal protein L11 561 112 0 0 3 0 0 1 4 4 4 5.2e-06 1 0.79 0.000069 0.039
33 ZFHX3 zinc finger homeobox 3 11148 8 0 1 5 3 0 6 14 13 14 0.000015 1 0.32 0.000076 0.042
34 MUC17 mucin 17, cell surface associated 13532 26 0 6 24 2 0 0 26 25 26 6.4e-06 1 0.79 0.000083 0.045
35 CDKN1B cyclin-dependent kinase inhibitor 1B (p27, Kip1) 605 133 0 0 0 1 0 4 5 5 5 0.000013 1 0.52 0.000093 0.048
SPOP

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

TP53

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

PTEN

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

CTNNB1

Figure S4.  This figure depicts the distribution of mutations and mutation types across the CTNNB1 significant gene.

FOXA1

Figure S5.  This figure depicts the distribution of mutations and mutation types across the FOXA1 significant gene.

ATM

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

PIK3CA

Figure S7.  This figure depicts the distribution of mutations and mutation types across the PIK3CA significant gene.

BRAF

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

HRAS

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

KDM6A

Figure S10.  This figure depicts the distribution of mutations and mutation types across the KDM6A significant gene.

IDH1

Figure S11.  This figure depicts the distribution of mutations and mutation types across the IDH1 significant gene.

SMG7

Figure S12.  This figure depicts the distribution of mutations and mutation types across the SMG7 significant gene.

ZMYM3

Figure S13.  This figure depicts the distribution of mutations and mutation types across the ZMYM3 significant gene.

EHHADH

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

TP53BP1

Figure S15.  This figure depicts the distribution of mutations and mutation types across the TP53BP1 significant gene.

CNTNAP1

Figure S16.  This figure depicts the distribution of mutations and mutation types across the CNTNAP1 significant gene.

BMP2K

Figure S17.  This figure depicts the distribution of mutations and mutation types across the BMP2K significant gene.

RPTN

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

TCEB3

Figure S19.  This figure depicts the distribution of mutations and mutation types across the TCEB3 significant gene.

NTM

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

MED12

Figure S21.  This figure depicts the distribution of mutations and mutation types across the MED12 significant gene.

MED15

Figure S22.  This figure depicts the distribution of mutations and mutation types across the MED15 significant gene.

ERN1

Figure S23.  This figure depicts the distribution of mutations and mutation types across the ERN1 significant gene.

LMOD2

Figure S24.  This figure depicts the distribution of mutations and mutation types across the LMOD2 significant gene.

FAM111A

Figure S25.  This figure depicts the distribution of mutations and mutation types across the FAM111A significant gene.

ZNF709

Figure S26.  This figure depicts the distribution of mutations and mutation types across the ZNF709 significant gene.

MLLT10

Figure S27.  This figure depicts the distribution of mutations and mutation types across the MLLT10 significant gene.

TNRC18

Figure S28.  This figure depicts the distribution of mutations and mutation types across the TNRC18 significant gene.

EMG1

Figure S29.  This figure depicts the distribution of mutations and mutation types across the EMG1 significant gene.

LAMA3

Figure S30.  This figure depicts the distribution of mutations and mutation types across the LAMA3 significant gene.

RPL11

Figure S31.  This figure depicts the distribution of mutations and mutation types across the RPL11 significant gene.

ZFHX3

Figure S32.  This figure depicts the distribution of mutations and mutation types across the ZFHX3 significant gene.

MUC17

Figure S33.  This figure depicts the distribution of mutations and mutation types across the MUC17 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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