LowPass Copy number analysis (GISTIC2)
Uterine Corpus Endometrioid Carcinoma (Primary solid tumor)
15 January 2014  |  analyses__2014_01_15
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/C17W69P5
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 2.0.20 (Firehose task version: 126).

Summary

There were 106 tumor samples used in this analysis: 18 significant arm-level results, 9 significant focal amplifications, and 0 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 - 9 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
3p11.1 9.3672e-09 5.1904e-08 chr3:90313861-94104854 5
19q12 0.00044789 0.00044789 chr19:29091305-30435531 10
17q12 0.0084206 0.0084206 chr17:37709781-38055678 12
1q21.3 0.036125 0.036125 chr1:120274286-151725787 146
3q26.2 0.053981 0.053981 chr3:168331862-168989980 2
3p25.2 0.088444 0.12837 chr3:10361004-13865852 28
8q24.21 0.1396 0.1396 chr8:129172563-129873439 0 [MIR1208]
18q11.2 0.14133 0.14133 chr18:13144299-24737313 55
11q13.3 0.15375 0.15375 chr11:67249837-71299215 53
Genes in Wide Peak

This is the comprehensive list of amplified genes in the wide peak for 3p11.1.

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

Genes
PROS1
NSUN3
ARL13B
DHFRL1
STX19
Genes in Wide Peak

This is the comprehensive list of amplified genes in the wide peak for 19q12.

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

Genes
CCNE1
UQCRFS1
URI1
POP4
PLEKHF1
C19orf12
LOC148145
LOC284395
VSTM2B
LOC100505835
Genes in Wide Peak

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

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

Genes
ERBB2
GRB7
NEUROD2
PNMT
TCAP
STARD3
IKZF3
PPP1R1B
MIEN1
PGAP3
ZPBP2
MIR4728
Genes in Wide Peak

This is the comprehensive list of amplified genes in the wide peak for 1q21.3.

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

Genes
ARNT
BCL9
NOTCH2
PDE4DIP
hsa-mir-554
hsa-mir-4257
hsa-mir-3118-3
hsa-mir-3118-2
hsa-mir-3118-1
CTSK
CTSS
ECM1
ENSA
FCGR1A
FCGR1B
FMO5
GJA5
GJA8
HMGCS2
MCL1
PDZK1
PI4KB
PRKAB2
PSMB4
PSMD4
RFX5
VPS72
TUFT1
HIST2H2AA3
HIST2H2AC
HIST2H2BE
HIST2H4A
PIP5K1A
ANXA9
ITGA10
PEX11B
SELENBP1
PRPF3
SEC22B
CHD1L
SETDB1
SV2A
RBM8A
SF3B4
PIAS3
SEMA6C
POLR3C
TXNIP
MTMR11
MLLT11
ADAM30
CD160
CELF3
VPS45
POGZ
RPRD2
CA14
NBPF14
PHGDH
RNF115
TMOD4
CERS2
BOLA1
APH1A
PLEKHO1
ACP6
GPR89B
MRPS21
ADAMTSL4
C1orf56
GOLPH3L
FAM63A
CDC42SE1
OTUD7B
FAM91A2
CGN
ZNF687
PRUNE
SCNM1
TNFAIP8L2
C1orf54
TARS2
SNX27
ANP32E
REG4
HORMAD1
POLR3GL
GNRHR2
GABPB2
HIST2H3C
LIX1L
C1orf51
HFE2
ANKRD35
BNIPL
PPIAL4A
PDIA3P
NBPF11
NUDT17
RIIAD1
NBPF15
ANKRD34A
HIST2H2AB
HIST2H3A
HIST2H2BC
HIST2H2BA
NBPF7
LOC375010
NOTCH2NL
FLJ39739
LOC388692
LYSMD1
NBPF9
HIST2H2BF
HIST2H4B
PPIAL4G
PPIAL4D
LOC645166
EMBP1
SRGAP2P2
PPIAL4B
LOC653513
GPR89A
PPIAL4C
HIST2H3D
FAM72B
MIR554
HIST2H2AA4
FAM72D
LOC728855
LOC728875
NBPF24
GPR89C
NBPF16
PDZK1P1
PPIAL4F
LOC728989
PPIAL4E
PFN1P2
LOC100130000
NBPF10
FCGR1C
LOC100286793
LOC100289211
MIR4257
TNFAIP8L2-SCNM1
Genes in Wide Peak

This is the comprehensive list of amplified genes in the wide peak for 3q26.2.

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

Genes
MECOM
EGFEM1P
Genes in Wide Peak

This is the comprehensive list of amplified genes in the wide peak for 3p25.2.

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

Genes
PPARG
RAF1
hsa-mir-885
ATP2B2
FBLN2
HRH1
RPL32
SEC13
SLC6A1
SLC6A11
SYN2
TIMP4
WNT7A
VGLL4
IQSEC1
ATG7
CAND2
NUP210
MKRN2
TMEM40
HDAC11
TSEN2
TAMM41
LOC285370
LOC285375
SNORA7A
MIR885
LOC100129480
Genes in Wide Peak

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

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

Genes
SS18
ZNF521
hsa-mir-320c-2
hsa-mir-1-2
hsa-mir-320c-1
hsa-mir-3156-2
AQP4
C18orf1
GATA6
LAMA3
MC2R
MC5R
NPC1
RBBP8
ROCK1
SNRPD1
TAF4B
RNMT
RIOK3
CABYR
C18orf8
IMPACT
MIB1
HRH4
CTAGE1
GREB1L
CHST9
TMEM241
CABLES1
ESCO1
OSBPL1A
FAM210A
TTC39C
PSMA8
CHST9-AS1
ANKRD29
ZNF519
ABHD3
CYP4F35P
KCTD1
ANKRD30B
POTEC
MIR1-2
MIR133A1
CXADRP3
ANKRD20A5P
LOC644669
LOC728606
LOC729950
LOC100288122
MIR320C1
MIR320C2
MIR3156-2
MIR4526
MIR4741
Genes in Wide Peak

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

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

Genes
CCND1
hsa-mir-548k
hsa-mir-3164
ALDH3B1
ALDH3B2
CHKA
CPT1A
DHCR7
CTTN
FGF3
FGF4
GSTP1
IGHMBP2
KRTAP5-9
LRP5
NDUFV1
NDUFS8
PPFIA1
FADD
AIP
PITPNM1
MTL5
FGF19
CDK2AP2
TCIRG1
SHANK2
MYEOV
GAL
SUV420H1
CABP2
C11orf24
ANO1
NADSYN1
PPP6R3
KRTAP5-8
UNC93B1
ACY3
MRGPRD
MRGPRF
MRPL21
TPCN2
ORAOV1
NUDT8
TBX10
KRTAP5-10
DOC2GP
FLJ42102
KRTAP5-7
KRTAP5-11
FAM86C2P
MIR548K
MIR3664
MIR4691

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.

Arm-level results

Table 2.  Get Full Table Arm-level significance table - 18 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 0.07 0.355 0.877 0.01 -2.05 0.996
1q 1955 0.40 14.7 0 0.02 -1.49 0.996
2p 924 0.18 4.62 1.27e-05 0.00 -2.5 0.996
2q 1556 0.14 3.4 0.0015 0.01 -2.03 0.996
3p 1062 0.12 2.06 0.0711 0.03 -1.33 0.996
3q 1139 0.15 3.64 0.00077 0.02 -1.66 0.996
4p 489 0.01 -2.43 0.994 0.01 -2.43 0.996
4q 1049 0.01 -2.3 0.994 0.03 -1.55 0.996
5p 270 0.08 0.324 0.877 0.06 -0.4 0.996
5q 1427 0.02 -1.75 0.994 0.08 0.564 0.881
6p 1173 0.10 1.28 0.288 0.02 -1.76 0.996
6q 839 0.07 -0.0121 0.918 0.02 -1.88 0.996
7p 641 0.15 3.11 0.00374 0.04 -0.943 0.996
7q 1277 0.15 3.44 0.00147 0.05 -0.371 0.996
8p 580 0.27 7.76 5.63e-14 0.12 1.95 0.182
8q 859 0.28 8.66 0 0.04 -0.997 0.996
9p 422 0.03 -1.46 0.994 0.12 1.82 0.182
9q 1113 0.02 -1.65 0.994 0.16 4.03 0.000566
10p 409 0.22 6.05 5.95e-09 0.04 -1.23 0.996
10q 1268 0.23 6.67 1.26e-10 0.06 -0.16 0.996
11p 862 0.04 -1.09 0.994 0.06 -0.347 0.996
11q 1515 0.07 0.242 0.888 0.04 -0.919 0.996
12p 575 0.10 1.39 0.258 0.00 -2.66 0.996
12q 1447 0.07 0.142 0.888 0.01 -2.17 0.996
13q 654 0.03 -1.54 0.994 0.06 -0.427 0.996
14q 1341 0.03 -1.39 0.994 0.06 -0.24 0.996
15q 1355 0.01 -2.16 0.994 0.09 0.911 0.603
16p 872 0.03 -1.45 0.994 0.08 0.417 0.967
16q 702 0.00 -2.5 0.994 0.20 5.28 2.63e-06
17p 683 0.01 -2.19 0.994 0.13 2.62 0.059
17q 1592 0.04 -0.813 0.994 0.11 1.9 0.182
18p 143 0.06 -0.352 0.994 0.11 1.44 0.33
18q 446 0.04 -1.06 0.994 0.12 1.87 0.182
19p 995 0.07 0.14 0.888 0.06 -0.235 0.996
19q 1709 0.06 0.0169 0.918 0.09 1.19 0.427
20p 355 0.11 1.38 0.258 0.02 -1.9 0.996
20q 753 0.09 1.07 0.381 0.00 -2.65 0.996
21q 509 0.03 -1.62 0.994 0.03 -1.62 0.996
22q 921 0.02 -1.81 0.994 0.10 1.19 0.427
Xq 1312 0.04 -0.88 0.994 0.11 1.8 0.182
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/UCEC-TP/6154884/segmentationfile.txt

  • Markers File = /xchip/cga/gdac-prod/tcga-gdac/jobResults/PrepareGisticDNASeq/UCEC-TP/6154884/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 3.  Get Full Table First 10 out of 106 Input Tumor Samples.

Tumor Sample Names
TCGA-A5-A0G5-01A-11D-A043-02
TCGA-A5-A0GB-01A-11D-A043-02
TCGA-A5-A0GD-01A-11D-A043-02
TCGA-A5-A0GE-01A-11D-A043-02
TCGA-A5-A0GJ-01A-11D-A043-02
TCGA-A5-A0GN-01A-11D-A043-02
TCGA-A5-A0GW-01A-11D-A043-02
TCGA-A5-A0GX-01A-11D-A043-02
TCGA-A5-A0R6-01A-11D-A101-02
TCGA-A5-A0R7-01A-31D-A101-02

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)