Mutation Analysis (MutSig 2CV v3.1)
Stomach and Esophageal carcinoma (Primary solid tumor)
02 April 2015  |  analyses__2015_04_02
Maintainer Information
Citation Information
doi:10.7908/C11R6PN1
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/C11R6PN1
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: STES-TP

  • Number of patients in set: 289

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:STES-TP.final_analysis_set.maf

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

  • Significantly mutated genes (q ≤ 0.1): 549

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: 549. 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 TP53 tumor protein p53 1314 16 0 1 88 18 8 34 148 137 89 6e-15 1e-05 1e-05 1e-16 4.1e-13
2 ARID1A AT rich interactive domain 1A (SWI-like) 6934 11 0 4 18 21 4 76 119 90 83 6.9e-16 1e-05 0.0024 1e-16 4.1e-13
3 RNF43 ring finger protein 43 2384 4 0 2 6 4 0 53 63 49 19 2.5e-16 1e-05 0.18 1e-16 4.1e-13
4 LARP4B La ribonucleoprotein domain family, member 4B 2283 1 0 2 6 1 0 22 29 27 8 1e-16 1e-05 0.78 1e-16 4.1e-13
5 XYLT2 xylosyltransferase II 2638 28 0 3 8 0 0 27 35 32 10 2.1e-13 1e-05 0.97 1.1e-16 4.1e-13
6 B2M beta-2-microglobulin 374 23 0 1 5 1 2 22 30 17 18 6.6e-15 0.00038 0.59 3.3e-16 1e-12
7 BZRAP1 benzodiazapine receptor (peripheral) associated protein 1 5698 3 0 5 13 1 0 33 47 46 17 1.1e-12 1e-05 1 4.4e-16 1.2e-12
8 KRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog 709 4 0 0 28 0 0 0 28 28 6 3.2e-11 1e-05 0.19 1.2e-14 2.6e-11
9 MLL2 myeloid/lymphoid or mixed-lineage leukemia 2 16826 1 0 12 42 4 1 55 102 65 73 3.5e-11 1e-05 0.98 1.3e-14 2.6e-11
10 GNG12 guanine nucleotide binding protein (G protein), gamma 12 227 0 0 2 2 0 0 9 11 11 3 1e-11 4e-05 0.45 3.5e-14 6.5e-11
11 LMAN1 lectin, mannose-binding, 1 1583 29 0 2 1 2 0 19 22 22 5 1.5e-10 1e-05 0.0036 5.3e-14 8.8e-11
12 CDH1 cadherin 1, type 1, E-cadherin (epithelial) 2709 30 0 4 23 0 4 3 30 29 27 9.4e-09 0.0014 1e-05 2.9e-12 4.2e-09
13 PLEKHA6 pleckstrin homology domain containing, family A member 6 3231 1 0 1 6 1 0 19 26 20 18 8e-10 2e-05 0.94 3e-12 4.2e-09
14 RHOA ras homolog gene family, member A 598 118 0 0 17 0 0 0 17 16 13 1.5e-09 0.00014 0.4 9.7e-12 1.3e-08
15 SMAD4 SMAD family member 4 1699 21 0 1 19 1 0 8 28 24 23 1.1e-08 6e-05 0.57 3.1e-11 3.8e-08
16 MTG1 mitochondrial GTPase 1 homolog (S. cerevisiae) 1045 0 0 0 1 0 0 8 9 9 3 1.3e-07 1e-05 1 3.7e-11 4.2e-08
17 KLF3 Kruppel-like factor 3 (basic) 1058 63 0 2 8 0 1 13 22 19 14 4.8e-09 7e-05 0.77 5.3e-11 5.7e-08
18 CTCF CCCTC-binding factor (zinc finger protein) 2224 4 0 2 6 0 1 12 19 18 11 2e-07 1e-05 0.049 5.6e-11 5.7e-08
19 ZBTB20 zinc finger and BTB domain containing 20 2238 0 0 8 17 0 0 21 38 28 19 3.7e-07 1e-05 0.92 1e-10 9.7e-08
20 GAS6 growth arrest-specific 6 2093 2 0 5 5 0 0 11 16 16 9 4.9e-07 1e-05 0.51 1.3e-10 1.2e-07
21 ATP6V1B1 ATPase, H+ transporting, lysosomal 56/58kDa, V1 subunit B1 (Renal tubular acidosis with deafness) 1596 4 0 2 8 1 0 13 22 20 10 4.9e-07 1e-05 1 1.3e-10 1.2e-07
22 PTEN phosphatase and tensin homolog (mutated in multiple advanced cancers 1) 1244 0 0 4 11 4 1 17 33 23 22 7e-07 1e-05 1 1.9e-10 1.5e-07
23 HLA-A major histocompatibility complex, class I, A 1128 0 0 0 5 0 0 11 16 15 9 4.6e-08 5e-05 1 2.7e-10 2.1e-07
24 FBXW7 F-box and WD repeat domain containing 7 2580 1 0 1 19 3 1 5 28 27 18 6.2e-09 0.0031 0.24 4.8e-10 3.6e-07
25 MVK mevalonate kinase 1235 8 0 0 5 0 0 8 13 13 6 2.8e-06 3e-05 0.002 7e-10 5.1e-07
26 FRMD4A FERM domain containing 4A 3216 1 0 2 4 0 0 14 18 18 6 3.5e-06 1e-05 0.0014 8.9e-10 6.2e-07
27 MBD6 methyl-CpG binding domain protein 6 3056 9 0 2 7 0 0 24 31 23 18 5.9e-06 1e-05 0.59 1.5e-09 9.9e-07
28 ZBTB7C zinc finger and BTB domain containing 7C 1866 1 0 6 5 0 0 12 17 15 8 0.000014 1e-05 0.12 3.3e-09 2.1e-06
29 JARID2 jumonji, AT rich interactive domain 2 3809 7 0 6 15 0 0 19 34 28 22 0.000021 1e-05 1 5e-09 3.1e-06
30 PAX6 paired box 6 1355 5 0 4 9 0 1 9 19 18 10 0.000029 1e-05 0.0014 6.6e-09 3.9e-06
31 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 3287 6 0 2 70 1 0 1 72 57 34 0.000029 1e-05 0.083 6.7e-09 3.9e-06
32 APC adenomatous polyposis coli 8592 2 0 7 21 12 1 19 53 42 46 6.2e-07 0.0004 0.98 1.3e-08 7.7e-06
33 NLK nemo-like kinase 1624 7 0 1 4 1 0 8 13 12 5 0.000073 1e-05 1 1.6e-08 8.8e-06
34 POLM polymerase (DNA directed), mu 1527 15 0 2 3 0 0 8 11 10 4 0.000074 1e-05 0.059 1.6e-08 8.8e-06
35 TMEM41A transmembrane protein 41A 813 1 0 0 1 0 0 5 6 6 2 8e-05 2e-05 0.0051 1.7e-08 9.1e-06
TP53

Figure S1.  This figure depicts the distribution of mutations and mutation types across the TP53 significant gene.

ARID1A

Figure S2.  This figure depicts the distribution of mutations and mutation types across the ARID1A significant gene.

RNF43

Figure S3.  This figure depicts the distribution of mutations and mutation types across the RNF43 significant gene.

LARP4B

Figure S4.  This figure depicts the distribution of mutations and mutation types across the LARP4B significant gene.

XYLT2

Figure S5.  This figure depicts the distribution of mutations and mutation types across the XYLT2 significant gene.

B2M

Figure S6.  This figure depicts the distribution of mutations and mutation types across the B2M significant gene.

BZRAP1

Figure S7.  This figure depicts the distribution of mutations and mutation types across the BZRAP1 significant gene.

KRAS

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

MLL2

Figure S9.  This figure depicts the distribution of mutations and mutation types across the MLL2 significant gene.

GNG12

Figure S10.  This figure depicts the distribution of mutations and mutation types across the GNG12 significant gene.

LMAN1

Figure S11.  This figure depicts the distribution of mutations and mutation types across the LMAN1 significant gene.

CDH1

Figure S12.  This figure depicts the distribution of mutations and mutation types across the CDH1 significant gene.

PLEKHA6

Figure S13.  This figure depicts the distribution of mutations and mutation types across the PLEKHA6 significant gene.

RHOA

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

SMAD4

Figure S15.  This figure depicts the distribution of mutations and mutation types across the SMAD4 significant gene.

MTG1

Figure S16.  This figure depicts the distribution of mutations and mutation types across the MTG1 significant gene.

KLF3

Figure S17.  This figure depicts the distribution of mutations and mutation types across the KLF3 significant gene.

CTCF

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

ZBTB20

Figure S19.  This figure depicts the distribution of mutations and mutation types across the ZBTB20 significant gene.

GAS6

Figure S20.  This figure depicts the distribution of mutations and mutation types across the GAS6 significant gene.

ATP6V1B1

Figure S21.  This figure depicts the distribution of mutations and mutation types across the ATP6V1B1 significant gene.

PTEN

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

HLA-A

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

FBXW7

Figure S24.  This figure depicts the distribution of mutations and mutation types across the FBXW7 significant gene.

MVK

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

FRMD4A

Figure S26.  This figure depicts the distribution of mutations and mutation types across the FRMD4A significant gene.

MBD6

Figure S27.  This figure depicts the distribution of mutations and mutation types across the MBD6 significant gene.

ZBTB7C

Figure S28.  This figure depicts the distribution of mutations and mutation types across the ZBTB7C significant gene.

JARID2

Figure S29.  This figure depicts the distribution of mutations and mutation types across the JARID2 significant gene.

PAX6

Figure S30.  This figure depicts the distribution of mutations and mutation types across the PAX6 significant gene.

PIK3CA

Figure S31.  This figure depicts the distribution of mutations and mutation types across the PIK3CA significant gene.

APC

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

NLK

Figure S33.  This figure depicts the distribution of mutations and mutation types across the NLK significant gene.

POLM

Figure S34.  This figure depicts the distribution of mutations and mutation types across the POLM 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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