Mutation Analysis (MutSig 2CV v3.1)
Colon Adenocarcinoma (Primary solid tumor)
02 April 2015  |  analyses__2015_04_02
Maintainer Information
Citation Information
doi:10.7908/C1028QJN
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/C1028QJN
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: COAD-TP

  • Number of patients in set: 367

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:COAD-TP.final_analysis_set.maf

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

  • Significantly mutated genes (q ≤ 0.1): 1354

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: 1354. 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 APC adenomatous polyposis coli 8592 0 0 169 273 283 8 103 667 295 372 1e-16 1e-05 1 1e-16 4.6e-13
2 TP53 tumor protein p53 1314 0 0 71 261 35 12 23 331 230 187 1e-16 1e-05 1e-05 1e-16 4.6e-13
3 ARID1A AT rich interactive domain 1A (SWI-like) 6934 4 0 17 46 18 0 19 83 72 63 1.2e-14 1e-05 0.087 1e-16 4.6e-13
4 RNF43 ring finger protein 43 2384 6 0 1 16 2 0 37 55 46 27 1e-16 1e-05 0.3 1e-16 4.6e-13
5 SOX9 SRY (sex determining region Y)-box 9 (campomelic dysplasia, autosomal sex-reversal) 1538 1 0 0 7 5 1 27 40 36 37 1e-16 0.036 0.47 3.3e-16 1.2e-12
6 MUC4 mucin 4, cell surface associated 3623 0 0 23 31 0 0 104 135 93 63 1e-16 1 0.24 1.2e-15 3.7e-12
7 RBM38 RNA binding motif protein 38 493 0 0 2 4 1 0 30 35 35 4 2.9e-16 1 0.8 1.1e-14 2.8e-11
8 ACVR1B activin A receptor, type IB 1679 9 0 0 21 6 0 3 30 26 25 1.7e-11 0.00012 0.12 4.9e-14 1.1e-10
9 B2M beta-2-microglobulin 374 4 0 1 8 2 5 6 21 16 16 1.6e-13 0.055 0.12 2.3e-13 4.7e-10
10 TXNDC2 thioredoxin domain-containing 2 (spermatozoa) 1672 46 0 2 5 1 0 19 25 22 9 2.6e-09 1e-05 0.97 8.5e-13 1.5e-09
11 SELPLG selectin P ligand 1217 20 0 1 5 0 0 12 17 16 9 1.3e-10 0.00011 0.57 1.3e-12 2.2e-09
12 FAM123B family with sequence similarity 123B 3412 25 0 6 19 24 0 9 52 49 40 3e-13 0.14 0.91 2.1e-12 3.2e-09
13 RBMX RNA binding motif protein, X-linked 1265 104 0 1 10 0 0 14 24 21 9 9.2e-09 1e-05 0.96 2.8e-12 4e-09
14 ZFP36L2 zinc finger protein 36, C3H type-like 2 1489 23 0 1 1 1 0 12 14 14 11 8.7e-11 0.0025 0.3 6.3e-12 8.2e-09
15 BCOR BCL6 co-repressor 5324 0 0 5 10 10 0 8 28 27 25 2.2e-10 0.063 0.0028 9.4e-12 1.1e-08
16 WNT1 wingless-type MMTV integration site family, member 1 1125 1 0 0 0 0 0 7 7 7 1 6.9e-08 1e-05 1e-05 2e-11 2.3e-08
17 CDH1 cadherin 1, type 1, E-cadherin (epithelial) 2709 0 0 18 66 9 9 4 88 74 65 1.7e-07 1e-05 0.3 4.8e-11 5.1e-08
18 NTAN1 N-terminal asparagine amidase 971 2 0 1 2 0 0 8 10 10 5 2.5e-07 1e-05 0.99 6.9e-11 7e-08
19 RHOA ras homolog gene family, member A 598 5 0 0 6 3 1 2 12 12 8 2.4e-09 0.0016 0.42 2.1e-10 2e-07
20 BMPR2 bone morphogenetic protein receptor, type II (serine/threonine kinase) 3165 8 0 5 20 12 1 7 40 35 37 1.1e-10 0.063 0.81 3e-10 2.7e-07
21 CRIPAK cysteine-rich PAK1 inhibitor 1341 43 0 2 7 1 0 10 18 18 10 1.5e-06 1e-05 0.0082 3.9e-10 3.4e-07
22 MVK mevalonate kinase 1235 18 0 2 5 0 1 10 16 15 7 4.9e-06 1e-05 0.00065 1.2e-09 1e-06
23 NF2 neurofibromin 2 (merlin) 1894 0 0 24 51 14 10 1 76 62 59 8.7e-06 1e-05 0.19 2.1e-09 1.7e-06
24 C15orf40 chromosome 15 open reading frame 40 1036 4 0 2 2 0 0 8 10 10 3 6.8e-07 1e-05 1 2.3e-09 1.7e-06
25 STARD3NL STARD3 N-terminal like 737 10 0 2 14 0 0 0 14 13 5 0.000011 2e-05 0.0024 2.7e-09 2e-06
26 OR4D10 olfactory receptor, family 4, subfamily D, member 10 936 91 0 2 15 0 0 0 15 14 9 0.000031 1e-05 0.02 7.1e-09 5e-06
27 FMN2 formin 2 5237 0 0 12 29 1 0 28 58 49 36 0.000032 1e-05 1 7.4e-09 5e-06
28 MAPK6 mitogen-activated protein kinase 6 2182 16 0 1 17 0 1 0 18 18 13 0.000067 1e-05 0.049 1.5e-08 9.6e-06
29 NR1H3 nuclear receptor subfamily 1, group H, member 3 1380 2 0 3 9 0 0 6 15 15 10 4.2e-06 0.00017 0.96 3.1e-08 2e-05
30 DIP2B DIP2 disco-interacting protein 2 homolog B (Drosophila) 4879 52 0 9 15 2 11 0 28 27 20 3.6e-06 0.00025 0.12 3.7e-08 0.000022
31 ATXN3L ataxin 3-like 1068 17 0 1 16 1 0 1 18 17 14 0.000017 1e-05 0.3 3.9e-08 0.000023
32 ALPK2 alpha-kinase 2 6561 12 0 13 41 1 0 11 53 42 39 0.00021 1e-05 0.77 4.4e-08 0.000025
33 P2RY13 purinergic receptor P2Y, G-protein coupled, 13 1071 6 0 2 14 1 0 0 15 15 11 0.000033 7e-05 0.052 7.5e-08 0.000041
34 ALG12 asparagine-linked glycosylation 12 homolog (S. cerevisiae, alpha-1,6-mannosyltransferase) 1503 0 0 0 2 0 0 5 7 7 5 0.000067 2e-05 0.95 8.2e-08 0.000043
35 UBQLN2 ubiquilin 2 1875 18 0 2 3 1 0 8 12 10 6 0.00041 1e-05 1 8.4e-08 0.000043
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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