Mutation Analysis (MutSig 2CV v3.1)
Brain Lower Grade Glioma (Primary solid tumor)
02 April 2015  |  analyses__2015_04_02
Maintainer Information
Citation Information
doi:10.7908/C1DR2TJ7
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/C1DR2TJ7
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: LGG-TP

  • Number of patients in set: 513

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:LGG-TP.final_analysis_set.maf

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

  • Significantly mutated genes (q ≤ 0.1): 106

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: 106. 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 IDH1 isocitrate dehydrogenase 1 (NADP+), soluble 1277 8 0 0 398 0 0 0 398 398 2 1e-16 1e-05 1 1e-16 2.3e-13
2 TP53 tumor protein p53 1890 21 0 2 247 19 13 40 319 248 145 1e-16 1e-05 1e-05 1e-16 2.3e-13
3 ATRX alpha thalassemia/mental retardation syndrome X-linked (RAD54 homolog, S. cerevisiae) 7615 1 0 7 32 47 20 118 217 194 185 1e-16 2e-05 0.18 1e-16 2.3e-13
4 CIC capicua homolog (Drosophila) 4905 6 0 1 66 9 3 48 126 108 89 1e-16 1e-05 0.61 1e-16 2.3e-13
5 NOTCH1 Notch homolog 1, translocation-associated (Drosophila) 7800 67 0 3 25 2 4 24 55 42 43 1e-16 1e-05 0.2 1e-16 2.3e-13
6 EGFR epidermal growth factor receptor (erythroblastic leukemia viral (v-erb-b) oncogene homolog, avian) 3999 35 0 1 43 2 0 1 46 35 29 1.1e-15 1e-05 0.033 1e-16 2.3e-13
7 PIK3R1 phosphoinositide-3-kinase, regulatory subunit 1 (alpha) 2361 7 0 2 7 1 1 15 24 22 18 5.2e-15 1e-05 0.65 1e-16 2.3e-13
8 IDH2 isocitrate dehydrogenase 2 (NADP+), mitochondrial 1401 82 0 0 20 0 0 0 20 20 3 6e-16 1e-05 1 1e-16 2.3e-13
9 NF1 neurofibromin 1 (neurofibromatosis, von Recklinghausen disease, Watson disease) 12120 12 0 2 11 12 7 21 51 33 47 1e-16 0.06 0.89 4.4e-16 9e-13
10 PTEN phosphatase and tensin homolog (mutated in multiple advanced cancers 1) 1244 64 1 0 15 3 2 4 24 24 22 1.8e-16 0.16 0.58 1.6e-15 2.8e-12
11 FUBP1 far upstream element (FUSE) binding protein 1 2013 1 1 1 1 11 9 29 50 47 45 2e-15 0.015 0.97 3e-15 5e-12
12 ARID1A AT rich interactive domain 1A (SWI-like) 6934 37 0 2 8 7 1 10 26 20 26 1e-16 1 0.85 3.8e-15 5.8e-12
13 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 3287 2 1 0 38 0 4 7 49 44 28 1.5e-09 1e-05 0.024 5.1e-13 7.1e-10
14 STK19 serine/threonine kinase 19 3763 12 0 0 3 0 0 8 11 10 4 1.9e-09 1e-05 0.55 6.1e-13 7.9e-10
15 NIPBL Nipped-B homolog (Drosophila) 8642 9 0 0 9 5 3 7 24 18 24 3.6e-13 1 0.64 1.1e-11 1.3e-08
16 CREBZF CREB/ATF bZIP transcription factor 1065 93 0 0 1 0 0 6 7 7 2 2.8e-07 1e-05 0.53 2.2e-10 2.6e-07
17 TCF12 transcription factor 12 (HTF4, helix-loop-helix transcription factors 4) 2278 11 0 0 0 0 1 15 16 15 15 6.1e-10 0.19 0.16 8.8e-10 9.5e-07
18 TRERF1 transcriptional regulating factor 1 3655 6 0 1 1 0 1 4 6 6 4 6e-06 3e-05 0.35 1.5e-09 1.5e-06
19 SRPX sushi-repeat-containing protein, X-linked 1431 40 0 0 0 0 0 4 4 4 1 3.2e-06 0.0001 1 1.2e-08 0.000012
20 SMARCA4 SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4 5189 18 0 5 23 0 0 6 29 26 26 2.4e-07 0.0015 0.44 1.6e-08 0.000015
21 EMG1 EMG1 nucleolar protein homolog (S. cerevisiae) 1360 183 0 0 0 1 0 6 7 7 3 5.3e-06 6e-05 0.92 2.2e-08 0.000019
22 FAM47C family with sequence similarity 47, member C 3110 53 0 4 18 0 0 0 18 18 8 0.00012 1e-05 0.61 2.7e-08 0.000022
23 TNRC18 trinucleotide repeat containing 18 9019 9 0 1 4 1 0 6 11 10 10 1.3e-08 0.089 0.94 3.3e-08 0.000027
24 DNMT3A DNA (cytosine-5-)-methyltransferase 3 alpha 2952 49 0 1 8 3 0 0 11 10 11 2.4e-08 1 0.087 1e-07 0.000077
25 HTRA2 HtrA serine peptidase 2 2436 3 0 0 1 0 0 4 5 5 2 0.000021 0.00021 0.74 1.8e-07 0.00013
26 ZNF709 zinc finger protein 709 1938 16 0 0 4 0 0 0 4 4 1 0.000097 0.0001 0.99 1.9e-07 0.00013
27 RBPJ recombination signal binding protein for immunoglobulin kappa J region 1606 17 0 0 1 1 0 5 7 7 6 2.5e-07 0.051 0.7 2.8e-07 0.00019
28 NRAS neuroblastoma RAS viral (v-ras) oncogene homolog 941 49 0 0 4 0 0 0 4 4 3 0.000059 0.00035 0.053 3.9e-07 0.00025
29 ZNF292 zinc finger protein 292 8202 7 0 2 7 0 0 11 18 14 18 3.3e-08 1 0.98 6.1e-07 0.00038
30 PTPN11 protein tyrosine phosphatase, non-receptor type 11 (Noonan syndrome 1) 1842 36 0 2 7 0 0 0 7 7 5 0.000092 0.0005 0.5 8.7e-07 0.00053
31 GAGE2D G antigen 2D 1115 284 0 0 0 0 0 5 5 5 1 0.0013 2e-05 0.78 1.7e-06 0.001
32 ARID2 AT rich interactive domain 2 (ARID, RFX-like) 5588 3 0 0 14 2 0 5 21 11 20 1.5e-06 0.14 0.22 2.3e-06 0.0013
33 ZMIZ1 zinc finger, MIZ-type containing 1 3288 22 0 0 5 0 0 4 9 9 7 0.00023 0.0011 0.2 2.4e-06 0.0013
34 PDGFRA platelet-derived growth factor receptor, alpha polypeptide 3358 0 0 5 14 0 0 4 18 10 16 0.017 0.0004 7e-05 2.8e-06 0.0015
35 ZNF512B zinc finger protein 512B 2743 10 0 0 5 0 1 0 6 5 4 0.02 1e-05 0.53 3.3e-06 0.0017
IDH1

Figure S1.  This figure depicts the distribution of mutations and mutation types across the IDH1 significant gene.

TP53

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

ATRX

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

CIC

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

NOTCH1

Figure S5.  This figure depicts the distribution of mutations and mutation types across the NOTCH1 significant gene.

EGFR

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

PIK3R1

Figure S7.  This figure depicts the distribution of mutations and mutation types across the PIK3R1 significant gene.

IDH2

Figure S8.  This figure depicts the distribution of mutations and mutation types across the IDH2 significant gene.

NF1

Figure S9.  This figure depicts the distribution of mutations and mutation types across the NF1 significant gene.

PTEN

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

FUBP1

Figure S11.  This figure depicts the distribution of mutations and mutation types across the FUBP1 significant gene.

ARID1A

Figure S12.  This figure depicts the distribution of mutations and mutation types across the ARID1A significant gene.

PIK3CA

Figure S13.  This figure depicts the distribution of mutations and mutation types across the PIK3CA significant gene.

STK19

Figure S14.  This figure depicts the distribution of mutations and mutation types across the STK19 significant gene.

NIPBL

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

CREBZF

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

TCF12

Figure S17.  This figure depicts the distribution of mutations and mutation types across the TCF12 significant gene.

TRERF1

Figure S18.  This figure depicts the distribution of mutations and mutation types across the TRERF1 significant gene.

SRPX

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

SMARCA4

Figure S20.  This figure depicts the distribution of mutations and mutation types across the SMARCA4 significant gene.

EMG1

Figure S21.  This figure depicts the distribution of mutations and mutation types across the EMG1 significant gene.

FAM47C

Figure S22.  This figure depicts the distribution of mutations and mutation types across the FAM47C significant gene.

TNRC18

Figure S23.  This figure depicts the distribution of mutations and mutation types across the TNRC18 significant gene.

DNMT3A

Figure S24.  This figure depicts the distribution of mutations and mutation types across the DNMT3A significant gene.

HTRA2

Figure S25.  This figure depicts the distribution of mutations and mutation types across the HTRA2 significant gene.

ZNF709

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

RBPJ

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

NRAS

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

ZNF292

Figure S29.  This figure depicts the distribution of mutations and mutation types across the ZNF292 significant gene.

PTPN11

Figure S30.  This figure depicts the distribution of mutations and mutation types across the PTPN11 significant gene.

ARID2

Figure S31.  This figure depicts the distribution of mutations and mutation types across the ARID2 significant gene.

ZMIZ1

Figure S32.  This figure depicts the distribution of mutations and mutation types across the ZMIZ1 significant gene.

PDGFRA

Figure S33.  This figure depicts the distribution of mutations and mutation types across the PDGFRA 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)
Copyright © 2015 Broad Institute TCGA GDAC as part of the TCGA Research Network. All rights reserved.
Made with Nozzle