Mutation Analysis (MutSigCV v0.6)
Head and Neck Squamous Cell Carcinoma (Primary solid tumor)
22 February 2013  |  analyses__2013_02_22
Maintainer Information
Citation Information
doi:10.7908/C1H41PMT
Maintained by Dan DiCara (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2013): Mutation Analysis (MutSigCV v0.6). Broad Institute of MIT and Harvard. doi:10.7908/C1H41PMT
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. MutSigCV v0.6 was used to generate the results found in this report.

  • Working with individual set: HNSC-TP

  • Number of patients in set: 306

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
Results
Target Coverage for Each Individual

The x axis represents the samples. The y axis represents the exons, one row per exon, and they are sorted by average coverage across samples. For exons with exactly the same average coverage, they are sorted next by the %GC of the exon. (The secondary sort is especially useful for the zero-coverage exons at the bottom).

Figure 1. 

Distribution of Mutation Counts, Coverage, and Mutation Rates Across Samples

Figure 2.  Patients counts and rates file used to generate this plot: HNSC-TP.patients.counts_and_rates.txt

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

  • nflank = number of noncoding mutations from this gene's flanking region, across the individual set

  • 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: 25. 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).

gene Nnon Nsil Nflank nnon npat nsite nsil nflank nnei fMLE p score time q
CASP8 445542 104346 62825 27 27 24 0 0 20 0.97 0 120 0.21 0
TP53 289170 84456 59760 253 214 158 5 0 4 2.7 7.8e-16 820 0.24 6.1e-12
FAT1 3253530 940598 115449 89 72 88 2 0 2 0.75 1e-15 320 0.22 6.1e-12
JUB 256420 75274 47147 19 18 19 1 0 20 0.98 2.4e-15 99 0.22 9.7e-12
CDKN2A 183760 52206 17712 66 65 31 0 0 6 0.86 2.7e-15 360 0.21 9.7e-12
PIK3CA 795320 203494 116776 65 64 24 0 0 20 0.86 6.7e-15 160 0.22 1.8e-11
NOTCH1 1222568 353330 110938 62 57 62 5 0 20 0.93 7.3e-15 210 0.22 1.8e-11
NSD1 1941890 548966 131704 38 33 38 1 0 20 0.47 8.3e-15 140 0.22 1.8e-11
MLL2 3240448 1071186 227189 61 56 61 3 0 20 0.87 9.1e-15 220 0.22 1.8e-11
EPHA2 653074 193720 83967 17 14 16 0 0 16 0.46 4.4e-11 73 0.21 8.1e-08
SULF1 652706 167078 114728 11 11 11 0 0 2 0 1.6e-08 47 0.21 0.000026
B2M 87826 24480 19152 7 7 6 0 0 20 0.82 1.7e-08 37 0.21 0.000026
NFE2L2 431158 114138 23717 18 17 13 0 0 20 0.77 7.1e-07 48 0.22 0.001
HRAS 141730 41018 24994 11 10 6 0 0 20 0.61 9.7e-07 34 0.2 0.0013
FBXW7 594264 163100 70535 16 15 14 1 0 20 0.82 2.9e-06 52 0.21 0.0036
FLG 2811614 834488 13134 60 48 60 9 0 15 0.92 9.3e-06 110 0.21 0.011
NECAB1 153276 37936 26558 7 6 7 2 0 20 0.88 0.000012 31 0.21 0.013
RB1 871544 229820 146936 10 10 10 2 0 20 0.61 0.000016 49 0.21 0.016
RASA1 710604 194944 143058 14 14 12 0 0 1 0.53 0.000027 58 0.22 0.026
ZNF750 502148 161568 12920 15 13 14 1 0 20 1.3 3e-05 56 0.21 0.027
HLA-A 250900 75882 45462 9 9 8 2 0 20 2 0.000047 49 0.21 0.041
ITGA8 756722 208076 172724 13 12 13 0 0 0 0 0.000053 45 0.21 0.044
TGFBR2 416168 111692 69792 11 10 9 1 0 20 1.4 0.000067 48 0.21 0.053
MTA2 497538 148712 105772 7 5 7 0 0 6 0 0.00011 23 0.19 0.084
CTCF 539786 138312 59979 13 11 13 1 0 20 0.9 0.00013 44 0.21 0.098
EP300 1751544 492046 185476 25 25 22 1 0 20 0.82 0.00015 72 0.22 0.11
PSIP1 409132 99758 115775 7 7 7 0 0 2 0.41 0.00018 35 0.21 0.12
BRWD3 1265260 341788 205542 19 16 19 0 0 1 0 0.00018 44 0.22 0.12
RAC1 145352 43758 35548 10 9 8 0 0 20 1.1 0.00021 27 0.2 0.13
IL32 124906 32752 32711 4 4 2 0 0 20 1 0.00025 25 0.21 0.15
KDM6A 946398 259164 150849 8 8 7 0 0 1 0 0.00025 40 0.21 0.15
CUL3 559700 143520 88663 10 10 10 1 0 20 0.64 0.00031 36 0.21 0.17
NPHP3 958098 257040 157997 8 8 8 0 0 3 0 0.00031 30 0.21 0.17
NOX1 393136 107690 70897 5 5 5 0 0 3 0 0.00033 20 0.22 0.18
STEAP4 326810 97920 23321 10 10 10 1 0 16 1.2 0.00034 36 0.21 0.18
TP53

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

FAT1

Figure S2.  This figure depicts the distribution of mutations and mutation types across the FAT1 significant gene.

JUB

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

CDKN2A

Figure S4.  This figure depicts the distribution of mutations and mutation types across the CDKN2A significant gene.

PIK3CA

Figure S5.  This figure depicts the distribution of mutations and mutation types across the PIK3CA significant gene.

NOTCH1

Figure S6.  This figure depicts the distribution of mutations and mutation types across the NOTCH1 significant gene.

NSD1

Figure S7.  This figure depicts the distribution of mutations and mutation types across the NSD1 significant gene.

MLL2

Figure S8.  This figure depicts the distribution of mutations and mutation types across the MLL2 significant gene.

EPHA2

Figure S9.  This figure depicts the distribution of mutations and mutation types across the EPHA2 significant gene.

SULF1

Figure S10.  This figure depicts the distribution of mutations and mutation types across the SULF1 significant gene.

B2M

Figure S11.  This figure depicts the distribution of mutations and mutation types across the B2M significant gene.

NFE2L2

Figure S12.  This figure depicts the distribution of mutations and mutation types across the NFE2L2 significant gene.

HRAS

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

FBXW7

Figure S14.  This figure depicts the distribution of mutations and mutation types across the FBXW7 significant gene.

FLG

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

NECAB1

Figure S16.  This figure depicts the distribution of mutations and mutation types across the NECAB1 significant gene.

RB1

Figure S17.  This figure depicts the distribution of mutations and mutation types across the RB1 significant gene.

RASA1

Figure S18.  This figure depicts the distribution of mutations and mutation types across the RASA1 significant gene.

ZNF750

Figure S19.  This figure depicts the distribution of mutations and mutation types across the ZNF750 significant gene.

HLA-A

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

ITGA8

Figure S21.  This figure depicts the distribution of mutations and mutation types across the ITGA8 significant gene.

TGFBR2

Figure S22.  This figure depicts the distribution of mutations and mutation types across the TGFBR2 significant gene.

MTA2

Figure S23.  This figure depicts the distribution of mutations and mutation types across the MTA2 significant gene.

CTCF

Figure S24.  This figure depicts the distribution of mutations and mutation types across the CTCF 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

This is an experimental feature. The full results of the analysis summarized in this report can be downloaded from the TCGA Data Coordination Center.

References
[1] TCGA, Integrated genomic analyses of ovarian carcinoma, Nature 474:609 - 615 (2011)
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