Mutation Analysis (MutSig 2CV v3.1)
Testicular Germ Cell Tumors (Primary solid tumor)
21 August 2015  |  analyses__2015_08_21
Maintainer Information
Citation Information
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/C190232R
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: TGCT-TP

  • Number of patients in set: 147

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:TGCT-TP.final_analysis_set.maf

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

  • Significantly mutated genes (q ≤ 0.1): 42

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: 42. 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 FAM18B2 family with sequence similarity 18, member B2 1003 303 0 0 26 0 0 0 26 26 1 1.1e-15 1e-05 0.64 1e-16 6.1e-13
2 KIT v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog 3013 130 0 0 24 0 2 1 27 26 13 1.1e-15 1e-05 1e-05 1e-16 6.1e-13
3 KRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog 709 122 0 0 19 0 0 0 19 19 7 1e-16 1e-05 0.003 1e-16 6.1e-13
4 FAM104B family with sequence similarity 104, member B 500 31 0 0 6 5 0 0 11 7 3 1e-08 1e-05 0.39 3.1e-12 1.4e-08
5 CSGALNACT2 chondroitin sulfate N-acetylgalactosaminyltransferase 2 1653 26 0 0 2 3 0 0 5 5 2 3.3e-07 9e-05 0.63 9.9e-10 3.2e-06
6 NRAS neuroblastoma RAS viral (v-ras) oncogene homolog 941 1000 0 0 7 0 0 0 7 7 4 4.2e-06 7e-05 0.086 1.1e-09 3.2e-06
7 DDX11 DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 11 (CHL1-like helicase homolog, S. cerevisiae) 3022 62 0 1 5 0 0 3 8 8 4 4.9e-06 1e-05 0.9 1.2e-09 3.2e-06
8 MUC6 mucin 6, oligomeric mucus/gel-forming 7450 34 0 3 15 0 0 0 15 15 11 0.000031 1e-05 0.76 7.1e-09 0.000016
9 PNPLA4 patatin-like phospholipase domain containing 4 786 541 0 0 5 0 0 0 5 5 1 0.00016 3e-05 0.054 3.4e-08 0.000068
10 SERINC2 serine incorporator 2 1404 20 0 0 3 0 1 0 4 4 2 0.000036 0.0001 0.95 7.4e-08 0.00013
11 RHPN2 rhophilin, Rho GTPase binding protein 2 2119 20 0 1 6 0 0 0 6 6 3 0.0013 0.0001 0.014 2.4e-07 0.00041
12 RBM10 RNA binding motif protein 10 2882 18 0 1 4 0 0 1 5 5 3 0.00012 0.00018 1 5.5e-07 0.00084
13 HSF4 heat shock transcription factor 4 1587 29 0 0 6 0 0 0 6 6 5 5.2e-07 0.059 0.79 6.9e-07 0.00097
14 CDC27 cell division cycle 27 homolog (S. cerevisiae) 2565 325 0 1 2 3 1 0 6 6 4 1.3e-06 0.033 0.52 9e-07 0.0012
15 MLLT3 myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated to, 3 1747 56 0 1 1 0 0 3 4 4 2 0.0014 0.0001 0.95 2.3e-06 0.0028
16 ERC1 ELKS/RAB6-interacting/CAST family member 1 3419 7 0 0 7 0 0 0 7 7 3 0.024 1e-05 0.0043 3.9e-06 0.0045
17 MEF2A myocyte enhancer factor 2A 1696 53 0 1 3 0 0 0 3 3 1 6e-05 0.013 0.069 6.4e-06 0.0069
18 SP8 Sp8 transcription factor 1533 29 0 0 6 0 0 0 6 6 1 0.00038 0.00085 0.98 0.000011 0.012
19 NAT10 N-acetyltransferase 10 3190 23 0 0 3 0 1 0 4 4 2 0.0082 0.0001 0.013 0.000012 0.012
20 SPIN2A spindlin family, member 2A 781 212 0 0 3 0 0 0 3 3 1 0.0012 0.001 0.28 0.000018 0.016
21 DEK DEK oncogene (DNA binding) 1168 12 0 0 5 0 0 0 5 5 2 0.0029 0.00028 1 0.000022 0.019
22 FANK1 fibronectin type III and ankyrin repeat domains 1 1078 414 0 0 0 4 0 0 4 4 1 0.00096 0.0016 1 0.000024 0.02
23 ANKRD11 ankyrin repeat domain 11 8036 68 0 3 7 0 0 0 7 7 5 0.015 9e-05 0.64 0.000027 0.022
24 C22orf43 chromosome 22 open reading frame 43 734 344 0 0 3 0 0 0 3 3 1 0.0026 0.001 0.97 0.000036 0.028
25 ATXN3 ataxin 3 1128 281 0 0 0 0 0 3 3 3 1 0.0031 0.001 0.99 0.000042 0.031
26 TPTE2 transmembrane phosphoinositide 3-phosphatase and tensin homolog 2 1649 1 0 2 0 0 5 0 5 5 1 0.065 4e-05 0.94 0.000044 0.031
27 KRTAP10-10 keratin associated protein 10-10 758 8 0 2 5 0 0 0 5 5 1 0.0023 0.00085 0.7 0.000051 0.034
28 ZNF680 zinc finger protein 680 1726 15 0 0 3 0 0 0 3 3 1 0.00033 0.096 0.2 0.000058 0.037
29 RAC1 ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) 660 132 0 0 3 0 1 0 4 4 3 0.00027 0.023 0.31 0.000059 0.037
30 NBPF10 neuroblastoma breakpoint family, member 10 10994 3 0 0 7 0 0 0 7 7 2 0.48 1e-05 1 0.000063 0.039
31 FAM8A1 family with sequence similarity 8, member A1 1258 270 0 0 0 3 0 0 3 3 1 0.0019 0.0049 0.46 0.000074 0.043
32 PSMD11 proteasome (prosome, macropain) 26S subunit, non-ATPase, 11 1321 274 0 0 4 0 0 0 4 4 1 0.00056 0.0043 0.61 0.000079 0.045
33 KRTAP1-1 keratin associated protein 1-1 536 687 0 0 3 0 0 0 3 3 1 0.0064 0.001 0.87 0.000084 0.046
34 OPLAH 5-oxoprolinase (ATP-hydrolysing) 3975 34 0 2 4 0 0 0 4 4 2 0.022 0.00036 0.82 0.0001 0.054
35 FAM101B family with sequence similarity 101, member B 440 255 0 0 3 1 0 0 4 4 3 0.00018 0.046 0.98 0.00012 0.061
KIT

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

KRAS

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

FAM104B

Figure S3.  This figure depicts the distribution of mutations and mutation types across the FAM104B significant gene.

CSGALNACT2

Figure S4.  This figure depicts the distribution of mutations and mutation types across the CSGALNACT2 significant gene.

NRAS

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

DDX11

Figure S6.  This figure depicts the distribution of mutations and mutation types across the DDX11 significant gene.

MUC6

Figure S7.  This figure depicts the distribution of mutations and mutation types across the MUC6 significant gene.

PNPLA4

Figure S8.  This figure depicts the distribution of mutations and mutation types across the PNPLA4 significant gene.

SERINC2

Figure S9.  This figure depicts the distribution of mutations and mutation types across the SERINC2 significant gene.

RHPN2

Figure S10.  This figure depicts the distribution of mutations and mutation types across the RHPN2 significant gene.

RBM10

Figure S11.  This figure depicts the distribution of mutations and mutation types across the RBM10 significant gene.

HSF4

Figure S12.  This figure depicts the distribution of mutations and mutation types across the HSF4 significant gene.

CDC27

Figure S13.  This figure depicts the distribution of mutations and mutation types across the CDC27 significant gene.

MLLT3

Figure S14.  This figure depicts the distribution of mutations and mutation types across the MLLT3 significant gene.

ERC1

Figure S15.  This figure depicts the distribution of mutations and mutation types across the ERC1 significant gene.

MEF2A

Figure S16.  This figure depicts the distribution of mutations and mutation types across the MEF2A significant gene.

SP8

Figure S17.  This figure depicts the distribution of mutations and mutation types across the SP8 significant gene.

NAT10

Figure S18.  This figure depicts the distribution of mutations and mutation types across the NAT10 significant gene.

SPIN2A

Figure S19.  This figure depicts the distribution of mutations and mutation types across the SPIN2A significant gene.

DEK

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

FANK1

Figure S21.  This figure depicts the distribution of mutations and mutation types across the FANK1 significant gene.

ANKRD11

Figure S22.  This figure depicts the distribution of mutations and mutation types across the ANKRD11 significant gene.

ATXN3

Figure S23.  This figure depicts the distribution of mutations and mutation types across the ATXN3 significant gene.

TPTE2

Figure S24.  This figure depicts the distribution of mutations and mutation types across the TPTE2 significant gene.

KRTAP10-10

Figure S25.  This figure depicts the distribution of mutations and mutation types across the KRTAP10-10 significant gene.

ZNF680

Figure S26.  This figure depicts the distribution of mutations and mutation types across the ZNF680 significant gene.

RAC1

Figure S27.  This figure depicts the distribution of mutations and mutation types across the RAC1 significant gene.

NBPF10

Figure S28.  This figure depicts the distribution of mutations and mutation types across the NBPF10 significant gene.

FAM8A1

Figure S29.  This figure depicts the distribution of mutations and mutation types across the FAM8A1 significant gene.

PSMD11

Figure S30.  This figure depicts the distribution of mutations and mutation types across the PSMD11 significant gene.

KRTAP1-1

Figure S31.  This figure depicts the distribution of mutations and mutation types across the KRTAP1-1 significant gene.

OPLAH

Figure S32.  This figure depicts the distribution of mutations and mutation types across the OPLAH 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)