LowPass Copy number analysis (GISTIC2)
Head and Neck Squamous Cell Carcinoma (Primary solid tumor)
16 April 2014  |  analyses__2014_04_16
Maintainer Information
Citation Information
Maintained by Spring Yingchun Liu (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2014): LowPass Copy number analysis (GISTIC2). Broad Institute of MIT and Harvard. doi:10.7908/C1QZ28KX
Overview
Introduction

GISTIC identifies genomic regions that are significantly gained or lost across a set of tumors. The pipeline first filters out normal samples from the segmented copy-number data by inspecting the TCGA barcodes and then executes GISTIC version 2.0.21 (Firehose task version: 127).

Summary

There were 108 tumor samples used in this analysis: 23 significant arm-level results, 10 significant focal amplifications, and 1 significant focal deletions were found.

Results
Focal results

Figure 1.  Genomic positions of amplified regions: the X-axis represents the normalized amplification signals (top) and significance by Q value (bottom). The green line represents the significance cutoff at Q value=0.25.

Table 1.  Get Full Table Amplifications Table - 10 significant amplifications found. Click the link in the last column to view a comprehensive list of candidate genes. If no genes were identified within the peak, the nearest gene appears in brackets.

Cytoband Q value Residual Q value Wide Peak Boundaries # Genes in Wide Peak
11q13.3 1.71e-29 1.71e-29 chr11:69545150-70374929 9
7p11.2 1.9965e-12 1.9965e-12 chr7:54959582-55684153 3
8p11.23 3.5867e-06 3.5867e-06 chr8:38021977-38562621 9
7q21.3 0.014542 0.014542 chr7:87928365-104608925 203
12q15 0.032041 0.032041 chr12:69017418-70739579 20
9p22.3 0.051479 0.051479 chr9:9870217-16803132 16
8q11.21 0.077813 0.077813 chr8:49126904-50064004 3
2q11.2 0.12902 0.12902 chr2:97149467-99094706 25
17q12 0.14197 0.14197 chr17:37561554-38464082 29
18q11.2 0.19237 0.19237 chr18:19750821-24904993 28
Genes in Wide Peak

This is the comprehensive list of amplified genes in the wide peak for 11q13.3.

Table S1.  Genes in bold are cancer genes as defined by The Sanger Institute: Cancer Gene Census[7].

Genes
hsa-mir-548k
CTTN
FGF3
FGF4
PPFIA1
FADD
SHANK2
ANO1
MIR548K
Genes in Wide Peak

This is the comprehensive list of amplified genes in the wide peak for 7p11.2.

Table S2.  Genes in bold are cancer genes as defined by The Sanger Institute: Cancer Gene Census[7].

Genes
EGFR
LANCL2
VOPP1
Genes in Wide Peak

This is the comprehensive list of amplified genes in the wide peak for 8p11.23.

Table S3.  Genes in bold are cancer genes as defined by The Sanger Institute: Cancer Gene Census[7].

Genes
FGFR1
WHSC1L1
BAG4
DDHD2
LSM1
PPAPDC1B
LETM2
RNF5P1
C8orf86
Genes in Wide Peak

This is the comprehensive list of amplified genes in the wide peak for 7q21.3.

Table S4.  Genes in bold are cancer genes as defined by The Sanger Institute: Cancer Gene Census[7].

Genes
CDK6
AKAP9
hsa-mir-548o
hsa-mir-4285
hsa-mir-106b
hsa-mir-591
hsa-mir-489
hsa-mir-1285-1
ACHE
ASNS
AZGP1
CALCR
KRIT1
AP1S1
COL1A2
CUX1
CYP3A7
CYP3A4
CYP3A5
CYP51A1
DLX5
DLX6
DYNC1I1
EPHB4
EPO
GNB2
GNG11
GNGT1
AGFG2
LRCH4
MCM7
NPTX2
OCM2
ORC5
SERPINE1
PCOLCE
PDK4
PEX1
CDK14
PMS2P1
POLR2J
PON1
PON2
PON3
RELN
PSMC2
TAC1
TAF6
TFR2
TRIP6
VGF
ZAN
ZNF3
ZKSCAN1
ZSCAN21
MTERF
SHFM1
TFPI2
TRRAP
FZD1
BUD31
SGCE
PLOD3
CLDN12
AP4M1
PMPCB
ATP5J2
MUC12
ARPC1B
RASA4
SLC25A13
LRRC17
POP7
BET1
ZNHIT1
ARPC1A
SH2B2
STAG3
CPSF4
COPS6
PDAP1
LMTK2
PEG10
ZKSCAN5
CLDN15
BRI3
TECPR1
PTCD1
FBXO24
STEAP1
DNAJC2
PILRB
PILRA
FIS1
ACTL6B
SRRT
ASB4
ANKIB1
ALKBH4
SAMD9
ZCWPW1
C7orf43
PPP1R9A
CCDC132
BAIAP2L1
MEPCE
SLC12A9
ACN9
SMURF1
GATAD1
MOSPD3
GIGYF1
RABL5
CYP3A43
CASD1
ZNF655
PVRIG
STEAP4
GAL3ST4
PRKRIP1
C7orf63
ORAI2
OR2AE1
TSC22D4
TRIM56
ARMC10
RBM48
ZNF394
MYH16
MGC16142
GTPBP10
TRIM4
MYL10
EMID2
MUC17
BHLHA15
SAMD9L
C7orf62
ZNF804B
ZNF498
FAM200A
PPP1R35
GPC2
LRWD1
FAM185A
FBXL13
NAPEPLD
TMEM130
NYAP1
CNPY4
POLR2J2
HEPACAM2
MBLAC1
FAM133B
STEAP2
DLX6-AS1
ZNF789
MOGAT3
GJC3
DPY19L2P2
GATS
NAT16
SLC26A5
LHFPL3
MGC72080
C7orf59
LRRD1
FLJ42280
KPNA7
C7orf61
UFSP1
MIR106B
MIR25
MIR93
SPDYE3
SPDYE2
DPY19L2P4
POLR2J3
MIR489
LOC645591
AZGP1P1
MIR591
LOC723809
MIR653
LOC728066
SPDYE6
RPL19P12
LOC100129845
UPK3BL
LOC100289187
LOC100289561
SPDYE2L
SAP25
MIR4285
MIR3609
LOC100506136
ATP5J2-PTCD1
MIR4653
MIR4652
MIR4467
MIR4658
LOC100630923
CYP3A7-CYP3AP1
Genes in Wide Peak

This is the comprehensive list of amplified genes in the wide peak for 12q15.

Table S5.  Genes in bold are cancer genes as defined by The Sanger Institute: Cancer Gene Census[7].

Genes
MDM2
hsa-mir-1279
CPM
LYZ
CNOT2
RAP1B
YEATS4
CCT2
FRS2
CPSF6
SLC35E3
NUP107
RAB3IP
BEST3
LRRC10
MIR1279
SNORA70G
MIR3913-2
MIR3913-1
LOC100507250
Genes in Wide Peak

This is the comprehensive list of amplified genes in the wide peak for 9p22.3.

Table S6.  Genes in bold are cancer genes as defined by The Sanger Institute: Cancer Gene Census[7].

Genes
NFIB
PTPRD
SNAPC3
TYRP1
MPDZ
CER1
PSIP1
BNC2
TTC39B
FREM1
C9orf93
LURAP1L
ZDHHC21
LOC389705
FLJ41200
C9orf146
Genes in Wide Peak

This is the comprehensive list of amplified genes in the wide peak for 8q11.21.

Table S7.  Genes in bold are cancer genes as defined by The Sanger Institute: Cancer Gene Census[7].

Genes
SNAI2
EFCAB1
C8orf22
Genes in Wide Peak

This is the comprehensive list of amplified genes in the wide peak for 2q11.2.

Table S8.  Genes in bold are cancer genes as defined by The Sanger Institute: Cancer Gene Census[7].

Genes
hsa-mir-3127
CNGA3
COX5B
INPP4A
ZAP70
ACTR1B
ARID5A
TMEM131
CNNM4
CNNM3
ANKRD39
FAM178B
SEMA4C
KANSL3
ANKRD36B
LMAN2L
FER1L5
NEURL3
FAHD2B
VWA3B
ANKRD23
ANKRD36
LOC728537
MIR3127
LOC100506123
Genes in Wide Peak

This is the comprehensive list of amplified genes in the wide peak for 17q12.

Table S9.  Genes in bold are cancer genes as defined by The Sanger Institute: Cancer Gene Census[7].

Genes
ERBB2
CDC6
CSF3
GRB7
NEUROD2
PNMT
MED1
PSMD3
THRA
TCAP
NR1D1
MED24
STARD3
CASC3
IKZF3
RAPGEFL1
CDK12
GSDMB
PPP1R1B
MIEN1
PGAP3
ORMDL3
ZPBP2
WIPF2
GSDMA
MSL1
SNORD124
LRRC3C
MIR4728
Genes in Wide Peak

This is the comprehensive list of amplified genes in the wide peak for 18q11.2.

Table S10.  Genes in bold are cancer genes as defined by The Sanger Institute: Cancer Gene Census[7].

Genes
SS18
ZNF521
hsa-mir-320c-2
AQP4
GATA6
LAMA3
NPC1
RBBP8
TAF4B
RIOK3
CABYR
C18orf8
IMPACT
HRH4
CTAGE1
CHST9
TMEM241
CABLES1
OSBPL1A
TTC39C
PSMA8
CHST9-AS1
ANKRD29
KCTD1
LOC728606
LOC729950
MIR320C2
MIR4741

Figure 2.  Genomic positions of deleted regions: the X-axis represents the normalized deletion signals (top) and significance by Q value (bottom). The green line represents the significance cutoff at Q value=0.25.

Table 2.  Get Full Table Deletions Table - 1 significant deletions found. Click the link in the last column to view a comprehensive list of candidate genes. If no genes were identified within the peak, the nearest gene appears in brackets.

Cytoband Q value Residual Q value Wide Peak Boundaries # Genes in Wide Peak
9p21.3 1.029e-14 1.029e-14 chr9:21969802-21994304 1
Genes in Wide Peak

This is the comprehensive list of deleted genes in the wide peak for 9p21.3.

Table S11.  Genes in bold are cancer genes as defined by The Sanger Institute: Cancer Gene Census[7].

Genes
CDKN2A
Arm-level results

Table 3.  Get Full Table Arm-level significance table - 23 significant results found. The significance cutoff is at Q value=0.25.

Arm # Genes Amp Frequency Amp Z score Amp Q value Del Frequency Del Z score Del Q value
1p 2121 0.05 0.104 0.965 0.05 0.104 0.734
1q 1955 0.12 3.05 0.00515 0.03 -1.02 0.999
2p 924 0.04 -2.45 0.999 0.02 -3.02 0.999
2q 1556 0.07 -0.431 0.999 0.03 -1.81 0.999
3p 1062 0.17 1.46 0.191 0.55 14.2 0
3q 1139 0.51 12.9 0 0.25 3.75 0.000512
4p 489 0.06 -2.14 0.999 0.21 2.24 0.0554
4q 1049 0.02 -2.63 0.999 0.15 1.49 0.193
5p 270 0.24 2.58 0.018 0.16 0.387 0.608
5q 1427 0.06 -0.696 0.999 0.28 7.14 6.09e-12
6p 1173 0.09 -0.343 0.999 0.07 -0.952 0.999
6q 839 0.06 -1.77 0.999 0.09 -0.931 0.999
7p 641 0.18 1.48 0.191 0.08 -1.45 0.999
7q 1277 0.12 0.947 0.404 0.09 0.00818 0.764
8p 580 0.26 3.22 0.00317 0.39 7.26 3.87e-12
8q 859 0.48 11.3 0 0.18 1.54 0.193
9p 422 0.23 2.12 0.0561 0.36 6.06 6.63e-09
9q 1113 0.29 5.9 2.49e-08 0.17 2.08 0.0749
10p 409 0.06 -2.29 0.999 0.19 1.52 0.193
10q 1268 0.03 -2.09 0.999 0.12 1.05 0.348
11p 862 0.09 -0.953 0.999 0.14 0.727 0.439
11q 1515 0.24 5.41 3.17e-07 0.22 4.74 6.97e-06
12p 575 0.19 1.79 0.113 0.05 -2.41 0.999
12q 1447 0.12 1.15 0.311 0.04 -1.5 0.999
13q 654 0.09 -1.19 0.999 0.16 0.948 0.361
14q 1341 0.17 3.01 0.00524 0.06 -1.14 0.999
15q 1355 0.05 -1.25 0.999 0.13 1.32 0.234
16p 872 0.10 -0.603 0.999 0.05 -2.01 0.999
16q 702 0.05 -2.25 0.999 0.09 -1.17 0.999
17p 683 0.09 -1.18 0.999 0.15 0.701 0.439
17q 1592 0.05 -1.09 0.999 0.03 -1.79 0.999
18p 143 0.18 0.499 0.687 0.18 0.738 0.439
18q 446 0.10 -1.08 0.999 0.35 5.99 8.57e-09
19p 995 0.04 -2.02 0.999 0.15 1.46 0.193
19q 1709 0.05 -0.667 0.999 0.12 1.88 0.109
20p 355 0.27 3.55 0.00128 0.10 -1.18 0.999
20q 753 0.26 4.2 0.000109 0.04 -2.35 0.999
21q 509 0.02 -3.16 0.999 0.17 1 0.351
22q 921 0.09 -0.607 0.999 0.12 0.246 0.672
Xq 1312 0.20 3.46 0.00153 0.18 2.84 0.0114
Methods & Data
Input
Description
  • Segmentation File: The segmentation file contains the segmented data for all the samples identified by GLAD, CBS, or some other segmentation algorithm. (See GLAD file format in the Genepattern file formats documentation.) It is a six column, tab-delimited file with an optional first line identifying the columns. Positions are in base pair units.The column headers are: (1) Sample (sample name), (2) Chromosome (chromosome number), (3) Start Position (segment start position, in bases), (4) End Position (segment end position, in bases), (5) Num markers (number of markers in segment), (6) Seg.CN (log2() -1 of copy number).

  • Markers File: The markers file identifies the marker names and positions of the markers in the original dataset (before segmentation). It is a three column, tab-delimited file with an optional header. The column headers are: (1) Marker Name, (2) Chromosome, (3) Marker Position (in bases).

  • Reference Genome: The reference genome file contains information about the location of genes and cytobands on a given build of the genome. Reference genome files are created in Matlab and are not viewable with a text editor.

  • CNV Files: There are two options for the cnv file. The first option allows CNVs to be identified by marker name. The second option allows the CNVs to be identified by genomic location. Option #1: A two column, tab-delimited file with an optional header row. The marker names given in this file must match the marker names given in the markers file. The CNV identifiers are for user use and can be arbitrary. The column headers are: (1) Marker Name, (2) CNV Identifier. Option #2: A 6 column, tab-delimited file with an optional header row. The 'CNV Identifier' is for user use and can be arbitrary. 'Narrow Region Start' and 'Narrow Region End' are also not used. The column headers are: (1) CNV Identifier, (2) Chromosome, (3) Narrow Region Start, (4) Narrow Region End, (5) Wide Region Start, (6) Wide Region End

  • Amplification Threshold: Threshold for copy number amplifications. Regions with a log2 ratio above this value are considered amplified.

  • Deletion Threshold: Threshold for copy number deletions. Regions with a log2 ratio below the negative of this value are considered deletions.

  • Cap Values: Minimum and maximum cap values on analyzed data. Regions with a log2 ratio greater than the cap are set to the cap value; regions with a log2 ratio less than -cap value are set to -cap. Values must be positive.

  • Broad Length Cutoff: Threshold used to distinguish broad from focal events, given in units of fraction of chromosome arm.

  • Remove X-Chromosome: Flag indicating whether to remove data from the X-chromosome before analysis. Allowed values= {1,0} (1: Remove X-Chromosome, 0: Do not remove X-Chromosome.

  • Confidence Level: Confidence level used to calculate the region containing a driver.

  • Join Segment Size: Smallest number of markers to allow in segments from the segmented data. Segments that contain fewer than this number of markers are joined to the neighboring segment that is closest in copy number.

  • Arm Level Peel Off: Flag set to enable arm-level peel-off of events during peak definition. The arm-level peel-off enhancement to the arbitrated peel-off method assigns all events in the same chromosome arm of the same sample to a single peak. It is useful when peaks are split by noise or chromothripsis. Allowed values= {1,0} (1: Use arm level peel off, 0: Use normal arbitrated peel-off).

  • Maximum Sample Segments: Maximum number of segments allowed for a sample in the input data. Samples with more segments than this threshold are excluded from the analysis.

  • Gene GISTIC: When enabled (value = 1), this option causes GISTIC to analyze deletions using genes instead of array markers to locate the lesion. In this mode, the copy number assigned to a gene is the lowest copy number among the markers that represent the gene.

Values

List of inputs used for this run of GISTIC2. All files listed should be included in the archived results.

  • Segmentation File = /xchip/cga/gdac-prod/tcga-gdac/jobResults/PrepareGisticDNASeq/HNSC-TP/8143049/segmentationfile.txt

  • Markers File = /xchip/cga/gdac-prod/tcga-gdac/jobResults/PrepareGisticDNASeq/HNSC-TP/8143049/markersfile.txt

  • Reference Genome = /xchip/cga/reference/gistic2/hg19_with_miR_20120227.mat

  • CNV Files = /xchip/cga/reference/gistic2/CNV.hg19.bypos.111213.txt

  • Amplification Threshold = 0.3

  • Deletion Threshold = 0.3

  • Cap Values = 2

  • Broad Length Cutoff = 0.5

  • Remove X-Chromosome = 0

  • Confidence Level = 0.99

  • Join Segment Size = 10

  • Arm Level Peel Off = 1

  • Maximum Sample Segments = 10000

  • Gene GISTIC = 0

Table 4.  Get Full Table First 10 out of 108 Input Tumor Samples.

Tumor Sample Names
TCGA-BA-4074-01A-01D-1431-02
TCGA-BA-4075-01A-01D-1431-02
TCGA-BA-4076-01A-01D-1431-02
TCGA-BA-4077-01B-01D-1431-02
TCGA-BA-4078-01A-01D-1431-02
TCGA-BA-5149-01A-01D-1509-02
TCGA-BA-5151-01A-01D-1431-02
TCGA-BA-5153-01A-01D-1431-02
TCGA-BA-5555-01A-01D-1509-02
TCGA-BA-5557-01A-01D-1509-02

Figure 3.  Segmented copy number profiles in the input data

Output
All Lesions File (all_lesions.conf_##.txt, where ## is the confidence level)

The all lesions file summarizes the results from the GISTIC run. It contains data about the significant regions of amplification and deletion as well as which samples are amplified or deleted in each of these regions. The identified regions are listed down the first column, and the samples are listed across the first row, starting in column 10.

Region Data

Columns 1-9 present the data about the significant regions as follows:

  1. Unique Name: A name assigned to identify the region.

  2. Descriptor: The genomic descriptor of that region.

  3. Wide Peak Limits: The 'wide peak' boundaries most likely to contain the targeted genes. These are listed in genomic coordinates and marker (or probe) indices.

  4. Peak Limits: The boundaries of the region of maximal amplification or deletion.

  5. Region Limits: The boundaries of the entire significant region of amplification or deletion.

  6. Q values: The Q value of the peak region.

  7. Residual Q values: The Q value of the peak region after removing ('peeling off') amplifications or deletions that overlap other, more significant peak regions in the same chromosome.

  8. Broad or Focal: Identifies whether the region reaches significance due primarily to broad events (called 'broad'), focal events (called 'focal'), or independently significant broad and focal events (called 'both').

  9. Amplitude Threshold: Key giving the meaning of values in the subsequent columns associated with each sample.

Sample Data

Each of the analyzed samples is represented in one of the columns following the lesion data (columns 10 through end). The data contained in these columns varies slightly by section of the file. The first section can be identified by the key given in column 9 - it starts in row 2 and continues until the row that reads 'Actual Copy Change Given.' This section contains summarized data for each sample. A '0' indicates that the copy number of the sample was not amplified or deleted beyond the threshold amount in that peak region. A '1' indicates that the sample had low-level copy number aberrations (exceeding the low threshold indicated in column 9), and a '2' indicates that the sample had high-level copy number aberrations (exceeding the high threshold indicated in column 9).The second section can be identified the rows in which column 9 reads 'Actual Copy Change Given.' The second section exactly reproduces the first section, except that here the actual changes in copy number are provided rather than zeroes, ones, and twos.The final section is similar to the first section, except that here only broad events are included. A 1 in the samples columns (columns 10+) indicates that the median copy number of the sample across the entire significant region exceeded the threshold given in column 9. That is, it indicates whether the sample had a geographically extended event, rather than a focal amplification or deletion covering little more than the peak region.

Amplification Genes File (amp_genes.conf_##.txt, where ## is the confidence level)

The amp genes file contains one column for each amplification peak identified in the GISTIC analysis. The first four rows are:

  1. Cytoband

  2. Q value

  3. Residual Q value

  4. Wide Peak Boundaries

These rows identify the lesion in the same way as the all lesions file.The remaining rows list the genes contained in each wide peak. For peaks that contain no genes, the nearest gene is listed in brackets.

Deletion Genes File (del_genes.conf_##.txt, where ## is the confidence level)

The del genes file contains one column for each deletion peak identified in the GISTIC analysis. The file format for the del genes file is identical to the format for the amp genes file.

Gistic Scores File (scores.gistic)

The scores file lists the Q values [presented as -log10(q)], G scores, average amplitudes among aberrant samples, and frequency of aberration, across the genome for both amplifications and deletions. The scores file is viewable with the Genepattern SNPViewer module and may be imported into the Integrated Genomics Viewer (IGV).

Segmented Copy Number (raw_copy_number.{fig|pdf|png} )

The segmented copy number is a pdf file containing a colormap image of the segmented copy number profiles in the input data.

Amplification Score GISTIC plot (amp_qplot.{fig|pdf|png|v2.pdf})

The amplification pdf is a plot of the G scores (top) and Q values (bottom) with respect to amplifications for all markers over the entire region analyzed.

Deletion Score GISTIC plot (del_qplot.{fig|pdf|png|v2.pdf})

The deletion pdf is a plot of the G scores (top) and Q values (bottom) with respect to deletions for all markers over the entire region analyzed.

Tables (table_{amp|del}.conf_##.txt, where ## is the confidence level)

Tables of basic information about the genomic regions (peaks) that GISTIC determined to be significantly amplified or deleted. These describe three kinds of peak boundaries, and list the genes contained in two of them. The region start and region end columns (along with the chromosome column) delimit the entire area containing the peak that is above the significance level. The region may be the same for multiple peaks. The peak start and end delimit the maximum value of the peak. The extended peak is the peak determined by robust, and is contained within the wide peak reported in {amp|del}_genes.txt by one marker.

Broad Significance Results (broad_significance_results.txt)

A table of per-arm statistical results for the data set. Each arm is a row in the table. The first column specifies the arm and the second column counts the number of genes known to be on the arm. For both amplification and deletion, the table has columns for the frequency of amplification or deletion of the arm, and a Z score and Q value.

Broad Values By Arm (broad_values_by_arm.txt)

A table of chromosome arm amplification levels for each sample. Each row is a chromosome arm, and each column a sample. The data are in units of absolute copy number -2.

All Data By Genes (all_data_by_genes.txt)

A gene-level table of copy number values for all samples. Each row is the data for a gene. The first three columns name the gene, its NIH locus ID, and its cytoband - the remaining columns are the samples. The copy number values in the table are in units of (copy number -2), so that no amplification or deletion is 0, genes with amplifications have positive values, and genes with deletions are negative values. The data are converted from marker level to gene level using the extreme method: a gene is assigned the greatest amplification or the least deletion value among the markers it covers.

Broad Data By Genes (broad_data_by_genes.txt)

A gene-level table of copy number data similar to the all_data_by_genes.txt output, but using only broad events with lengths greater than the broad length cutoff. The structure of the file and the methods and units used for the data analysis are otherwise identical to all_data_by_genes.txt.

Focal Data By Genes (focal_data_by_genes.txt)

A gene-level table of copy number data similar to the all_data_by_genes.txt output, but using only focal events with lengths greater than the focal length cutoff. The structure of the file and the methods and units used for the data analysis are otherwise identical to all_data_by_genes.txt.

All Thresholded By Genes (all_thresholded.by_genes.txt)

A gene-level table of discrete amplification and deletion indicators at for all samples. There is a row for each gene. The first three columns name the gene, its NIH locus ID, and its cytoband - the remaining columns are the samples. A table value of 0 means no amplification or deletion above the threshold. Amplifications are positive numbers: 1 means amplification above the amplification threshold; 2 means amplifications larger to the arm level amplifications observed for the sample. Deletions are represented by negative table values: -1 represents deletion beyond the threshold; -2 means deletions greater than the minimum arm-level deletion observed for the sample.

Sample Cutoffs (sample_cutoffs.txt)

A table of the per-sample threshold cutoffs (in units of absolute copy number -2) used to distinguish the high level amplifications (+/-2) from ordinary amplifications (+/-1) in the all_thresholded.by_genes.txt output file. The table contains three columns: the sample identifier followed by the low (deletion) and high (amplification) cutoff values. The cutoffs are calculated as the minimum arm-level amplification level less the deletion threshold for deletions and the maximum arm-level amplification plus the amplification threshold for amplifications.

Focal Input To Gistic (focal_input.seg.txt)

A list of copy number segments describing just the focal events present in the data. The segment amplification/deletion levels are in units of (copy number -2), with amplifications positive and deletions negative numbers. This file may be viewed with IGV.

Gene Counts vs. Copy Number Alteration Frequency (freqarms_vs_ngenes.{fig|pdf})

An image showing the correlation between gene counts and frequency of copy number alterations.

Confidence Intervals (regions_track.conf_##.bed, where ## is the confidence level)

A file indicating the position of the confidence intervals around GISTIC peaks that can be loaded as a track in a compatible viewer browser such as IGV or the UCSC genome browser.

GISTIC

GISTIC identifies genomic regions that are significantly gained or lost across a set of tumors. It takes segmented copy number ratios as input, separates arm-level events from focal events, and then performs two tests: (i) identifies significantly amplified/deleted chromosome arms; and (ii) identifies regions that are significantly focally amplified or deleted. For the focal analysis, the significance levels (Q values) are calculated by comparing the observed gains/losses at each locus to those obtained by randomly permuting the events along the genome to reflect the null hypothesis that they are all 'passengers' and could have occurred anywhere. The locus-specific significance levels are then corrected for multiple hypothesis testing. The arm-level significance is calculated by comparing the frequency of gains/losses of each arm to the expected rate given its size. The method outputs genomic views of significantly amplified and deleted regions, as well as a table of genes with gain or loss scores. A more in depth discussion of the GISTIC algorithm and its utility is given in [1], [3], and [5].

CNV Description

Regions of the genome that are prone to germ line variations in copy number are excluded from the GISTIC analysis using a list of germ line copy number variations (CNVs). A CNV is a DNA sequence that may be found at different copy numbers in the germ line of two different individuals. Such germ line variations can confound a GISTIC analysis, which finds significant somatic copy number variations in cancer. A more in depth discussion is provided in [6]. GISTIC currently uses two CNV exclusion lists. One is based on the literature describing copy number variation, and a second one comes from an analysis of significant variations among the blood normals in the TCGA data set.

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] Beroukhim et al, Assessing the significance of chromosomal aberrations in cancer: Methodology and application to glioma, Proc Natl Acad Sci U S A. Vol. 104:50 (2007)
[3] Mermel et al, GISTIC2.0 facilitates sensitive and confident localization of the targets of focal somatic copy-number alteration in human cancers, Genome Biology Vol. 12:4 (2011)
[5] Beroukhim et al., The landscape of somatic copy-number alteration across human cancers, Nature Vol. 463:7283 (2010)
[6] McCarroll, S. A. et al., Integrated detection and population-genetic analysis of SNPs and copy number variation, Nat Genet Vol. 40(10):1166-1174 (2008)