LowPass Copy number analysis (GISTIC2)
Breast Invasive 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/C1S46QH8
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 19 tumor samples used in this analysis: 15 significant arm-level results, 2 significant focal amplifications, and 2 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 - 2 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
8p11.23 0.16436 0.16436 chr8:36121788-39714022 33
20q13.2 0.21956 0.21956 chr20:46463398-63025520 200
Genes in Wide Peak

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

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

Genes
FGFR1
WHSC1L1
ADRB3
ADAM3A
EIF4EBP1
ADAM2
STAR
TACC1
ADAM18
ADAM9
ASH2L
BAG4
ERLIN2
PROSC
DDHD2
GPR124
LSM1
BRF2
PLEKHA2
ZNF703
RAB11FIP1
TM2D2
PPAPDC1B
GOT1L1
LETM2
KCNU1
HTRA4
ADAM32
ADAM5P
RNF5P1
C8orf86
LOC728024
LOC100130964
Genes in Wide Peak

This is the comprehensive list of amplified genes in the wide peak for 20q13.2.

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

Genes
GNAS
SS18L1
hsa-mir-647
hsa-mir-4326
hsa-mir-124-3
hsa-mir-133a-2
hsa-mir-3195
hsa-mir-1257
hsa-mir-646
hsa-mir-298
hsa-mir-4325
hsa-mir-1302-5
hsa-mir-1259
hsa-mir-3194
ATP5E
BMP7
CDH4
CEBPB
CHRNA4
COL9A3
CSE1L
CSTF1
CTSZ
CYP24A1
EDN3
EEF1A2
NPBWR2
KCNB1
KCNG1
KCNQ2
LAMA5
MC3R
MYT1
NFATC2
NTSR1
OPRL1
PCK1
PFDN4
PPP1R3D
PSMA7
PTGIS
PTK6
PTPN1
RPS21
SNAI1
SRMS
STAU1
AURKA
TAF4
TCEA2
TFAP2C
TPD52L2
UBE2V1
ZNF217
RAE1
BCAS1
STX16
TNFRSF6B
DPM1
VAPB
B4GALT5
SPATA2
OSBPL2
ATP9A
ARFRP1
RGS19
SYCP2
ARFGEF2
TCFL5
ADRM1
OGFR
DIDO1
HRH3
SLC9A8
ADNP
SPO11
PRPF6
GTPBP5
GMEB2
SNORD12C
MOCS3
SLCO4A1
STMN3
SLMO2
TH1L
C20orf43
RTEL1
SOX18
YTHDF1
LIME1
UCKL1
C20orf11
PCMTD2
C20orf20
PPP4R1L
RBM38
BCAS4
DDX27
ZFP64
ARFGAP1
DOK5
RNF114
SLC2A4RG
PMEPA1
CASS4
SALL4
ZNFX1
RAB22A
ZNF512B
PREX1
COL20A1
CDH26
SLC17A9
LOC63930
FAM217B
C20orf195
PPDPF
BIRC7
NPEPL1
DNAJC5
TUBB1
ZBP1
CABLES2
PARD6B
ZGPAT
PRIC285
FAM210B
PHACTR3
BHLHE23
NKAIN4
TSHZ2
C20orf85
ZNF831
C20orf166
GATA5
ZBTB46
GCNT7
CBLN4
CTCFL
SAMD10
ABHD16B
LINC00266-1
FAM65C
C20orf151
LOC149773
GNAS-AS1
LSM14B
APCDD1L
C20orf201
FAM209A
C20orf166-AS1
LINC00176
LINC00494
LOC284751
C20orf197
LOC284757
TMEM189
TMEM189-UBE2V1
FAM209B
SUMO1P1
MIR1-1
MIR124-3
MIR133A2
MIR296
ZNFX1-AS1
SNORD12
MIR645
MIR647
HAR1A
HAR1B
UCKL1-AS1
SNORD12B
MIR298
MIR941-1
MIR941-4
MIR941-2
MIR941-3
LOC100127888
DPH3P1
LINC00029
LOC100144597
FLJ16779
MIR1914
MIR1257
MIR4325
MIR3194
MIR4326
MIR3196
MTRNR2L3
LOC100505815
LOC100506384
RTEL1-TNFRSF6B
SLMO2-ATP5E
STX16-NPEPL1
MIR4756
MIR4758
MIR4532
MIR4533
MIR5095
LOC100652730

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 - 2 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
8p21.3 0.17922 0.17922 chr8:1-26298992 211
11q22.3 0.17922 0.17922 chr11:78569205-135006516 414
Genes in Wide Peak

This is the comprehensive list of deleted genes in the wide peak for 8p21.3.

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

Genes
PCM1
hsa-mir-320a
hsa-mir-548v
hsa-mir-383
hsa-mir-598
hsa-mir-1322
hsa-mir-4286
hsa-mir-124-1
hsa-mir-597
hsa-mir-548i-3
hsa-mir-596
NAT1
NAT2
ANGPT2
ASAH1
ATP6V1B2
BLK
BMP1
POLR3D
BNIP3L
CTSB
DEFA1
DEFA3
DEFA4
DEFA5
DEFA6
DEFB1
DEFB4A
EGR3
EPB49
CLN8
FDFT1
FGL1
GATA4
GFRA2
GNRH1
LOXL2
LPL
MSR1
MSRA
NEFM
NEFL
NKX3-1
PDGFRL
PPP2R2A
PPP3CC
SFTPC
SLC7A2
SLC18A1
STC1
TUSC3
TNKS
ADAM7
TNFRSF10D
TNFRSF10C
TNFRSF10B
TNFRSF10A
FGF17
DOK2
MTMR7
MYOM2
DLGAP2
MFHAS1
ENTPD4
ARHGEF10
PHYHIP
KBTBD11
SORBS3
NPM2
DLC1
SPAG11B
ADAM28
LZTS1
XPO7
RHOBTB2
PSD3
SLC39A14
FBXO25
FGF20
ADAMDEC1
CNOT7
ZDHHC2
SLC25A37
KCTD9
PINX1
PIWIL2
INTS10
AGPAT5
CSGALNACT1
HR
DEFB103B
BIN3
MTUS1
KIAA1456
KIAA1967
SH2D4A
PDLIM2
CSMD1
EBF2
FAM160B2
MTMR9
MCPH1
PPP1R3B
NUDT18
DOCK5
FLJ14107
REEP4
SOX7
FAM167A
SLC35G5
LINC00208
C8orf12
FAM86B1
ERI1
LONRF1
CHMP7
RP1L1
CLDN23
VPS37A
NKX2-6
SGCZ
DEFB104A
LOC157273
SGK223
PEBP4
CDCA2
LOC157627
C8orf42
ERICH1
TDH
C8orf48
ZNF596
DEFT1P
R3HCC1
PRSS55
C8orf74
LGI3
DEFB105A
DEFB106A
DEFB107A
DEFB109P1
DEFB130
NEIL2
LOC254896
FLJ10661
XKR6
LOC286059
LOC286083
EFHA2
LOC286114
LOC340357
LOC349196
USP17L2
XKR5
FAM90A25P
LOC389641
LOC392196
MIR124-1
MIR320A
DEFB103A
OR4F21
FAM90A13
FAM90A5
FAM90A7
FAM90A8
FAM90A18
FAM90A9
FAM90A10
DEFA10P
MIR383
DEFB107B
DEFB104B
DEFB106B
DEFB105B
C8orf58
DEFB135
DEFB136
DEFB134
DEFB109P1B
RPL23AP53
FAM90A14
FAM86B2
SPAG11A
MIR596
MIR597
MIR598
DEFA1B
FAM90A20
FAM90A19
ZNF705D
FAM66B
LOC100128993
ZNF705G
FAM66E
LOC100132396
FAM66D
FAM66A
LOC100133267
LOC100287015
DEFT1P2
DEFB4B
MIR1322
MIR548I3
MIR3926-2
MIR3926-1
LOC100506990
LOC100507156
MIR4659A
MIR4660
MIR4659B
LOC100652791
Genes in Wide Peak

This is the comprehensive list of deleted genes in the wide peak for 11q22.3.

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

Genes
BIRC3
ATM
CBL
DDX6
DDX10
FLI1
MLL
PAFAH1B2
POU2AF1
SDHD
PICALM
PCSK7
ARHGEF12
MAML2
hsa-mir-3167
hsa-mir-100
hsa-mir-4301
hsa-mir-34c
hsa-mir-1260b
hsa-mir-548l
hsa-mir-1304
hsa-mir-1261
hsa-mir-3166
hsa-mir-4300
hsa-mir-708
ACAT1
ACRV1
BIRC2
APLP2
APOA1
APOA4
APOC3
ARCN1
FXYD2
CXCR5
CASP1
CASP4
CASP5
CD3D
CD3E
CD3G
CTSC
CHEK1
CRYAB
DLAT
DLG2
DPAGT1
DRD2
ETS1
FDX1
FUT4
SLC37A4
GRIA4
GRIK4
GRM5
GUCY1A2
H2AFX
HMBS
HSPA8
HSPB2
HTR3A
IL10RA
IL18
STT3A
KCNJ1
KCNJ5
VWA5A
MCAM
MMP1
MMP3
MMP7
MMP8
MMP10
MMP12
MMP13
MRE11A
MTNR1B
NCAM1
NFRKB
NNMT
NPAT
NRGN
OPCML
PGR
PPP2R1B
PRCP
PTS
PVRL1
RDX
RPS25
SC5DL
SCN2B
SCN4B
ST3GAL4
SLN
SORL1
SRPR
ST14
TAGLN
TECTA
THY1
TRPC6
TYR
UPK2
ZBTB16
ZNF202
CUL5
FZD4
BARX2
OR7E2P
JRKL
EED
ZNF259
MTMR2
USP2
HTR3B
ZW10
MMP20
UBE4A
MED17
EI24
FEZ1
CEP57
ARHGAP32
C2CD2L
NAALAD2
RBM7
MPZL2
YAP1
HYOU1
ATP5L
ME3
GPR83
SRSF8
ADAMTS8
PRSS23
TREH
CEP164
IGSF9B
ENDOD1
EXPH5
PHLDB1
SIK2
NCAPD3
SIK3
VSIG2
BACE1
TRIM29
RAB38
CADM1
PANX1
POU2F3
HINFP
REXO2
ODZ4
OR8G2
OR8B8
OR8G1
TIMM8B
OR8B2
CHORDC1
ACAD8
B3GAT1
RAB30
DCPS
C11orf54
ZBTB44
THYN1
DDX25
NOX4
NTM
CDON
SIDT2
TRAPPC4
C11orf73
CWC15
PCF11
SPA17
FXYD6
CNTN5
SIAE
C11orf71
ROBO4
SLC35F2
RAB39A
BTG4
FAM55D
SYTL2
ANKRD49
TTC12
C11orf57
ELMOD1
FOXRED1
KDM4D
SCN3B
VPS11
TMEM126B
TEX12
CRTAM
TMPRSS4
IFT46
C11orf75
PRDM10
TRIM49
DSCAML1
GRAMD1B
KIAA1377
ARHGAP20
USP28
CREBZF
CARD18
CCDC90B
CCDC81
AASDHPPT
PKNOX2
TP53AIP1
MMP27
ABCG4
ROBO3
C11orf1
TMEM135
TAF1D
RNF26
FAM118B
DYNC2H1
NLRX1
C11orf61
CCDC82
ALG9
CLMP
PDZD3
C11orf63
CCDC15
PDGFD
TMPRSS5
PUS3
MFRP
JAM3
BCO2
TMEM133
TMPRSS13
TMEM126A
DCUN1D5
KIAA1826
KIRREL3
BUD13
TMEM25
RPUSD4
TBRG1
UBASH3B
C11orf70
DIXDC1
KIAA1731
ZC3H12C
GLB1L2
ESAM
ALKBH8
FDXACB1
C11orf52
VPS26B
GLB1L3
TIRAP
CARD16
C1QTNF5
TMEM123
PANX3
APOA5
SLC36A4
FAT3
TRIM64
TMEM45B
C11orf93
PIH1D2
FAM55A
FAM55B
AMICA1
FAM76B
SESN3
PIWIL4
ARHGAP42
KBTBD3
CWF19L2
KDELC2
LAYN
TTC36
AMOTL1
CCDC67
PATE1
C11orf65
ADAMTS15
MPZL3
FOLH1B
C11orf45
HYLS1
TMEM218
SLC37A2
OR8B12
OR8G5
OR10G8
OR10G9
OR10S1
OR6T1
OR4D5
TBCEL
TMEM136
SPATA19
C11orf82
CCDC83
HEPACAM
OAF
FAM181B
CCDC89
ANGPTL5
ANKK1
RNF214
LOC283143
BCL9L
FOXR1
CCDC153
OR8D1
OR8D2
OR8B4
KIRREL3-AS3
LOC283174
LOC283177
CCDC84
TMEM225
OR8D4
ANKRD42
C11orf53
LOC341056
HEPHL1
C11orf34
VSTM5
TRIM77P
FOLR4
KDM4DL
BSX
OR6X1
OR6M1
OR10G4
OR10G7
OR8B3
OR8A1
LOC399939
LOC399940
C11orf87
C11orf92
C11orf88
MIR100HG
PATE2
PATE4
FLJ39051
SNX19
MIRLET7A2
MIR100
MIR125B1
MIR34B
MIR34C
DDI1
BLID
CARD17
LINC00167
SCARNA9
HEPN1
TRIM64B
TRIM53P
TRIM49L2
UBTFL1
LOC643037
LOC643733
LOC643923
CLDN25
LOC649133
RPL23AP64
SNORA8
SNORA1
SNORA18
SNORA40
SNORA25
SNORA32
SNORD5
SNORD6
TRIM49L1
MIR708
LOC100128239
LOC100132078
PATE3
LOC100288077
LOC100288346
MIR1304
SNORA70E
BACE1-AS
MIR4300
MIR4301
MIR3167
MIR1260B
LOC100499227
MIR3920
MIR3656
LOC100506233
LOC100506368
CASP12
LOC100507392
LOC100526771
HSPB2-C11orf52
FXYD6-FXYD2
MIR4697
MIR4490
MIR4493
MIR4491
MIR4492
MIR4693
LOC100652768
Arm-level results

Table 3.  Get Full Table Arm-level significance table - 15 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 0.12 0.367 0.978 0.12 0.367 0.621
1q 1955 0.71 8.16 4.44e-15 0.29 1.59 0.203
2p 924 0.00 -1.89 0.978 0.11 -0.79 0.884
2q 1556 0.00 -1.6 0.978 0.11 -0.328 0.884
3p 1062 0.00 -1.83 0.978 0.11 -0.697 0.884
3q 1139 0.11 -0.643 0.978 0.00 -1.79 0.964
4p 489 0.00 -2.02 0.978 0.16 -0.496 0.884
4q 1049 0.12 -0.53 0.978 0.12 -0.53 0.884
5p 270 0.18 -0.422 0.978 0.12 -0.907 0.884
5q 1427 0.18 0.44 0.978 0.12 -0.167 0.871
6p 1173 0.13 -0.251 0.978 0.24 0.889 0.44
6q 839 0.00 -1.69 0.978 0.32 1.54 0.203
7p 641 0.29 1.05 0.976 0.14 -0.478 0.884
7q 1277 0.22 0.861 0.978 0.07 -0.902 0.884
8p 580 0.00 -1.57 0.978 0.47 3.02 0.0167
8q 859 0.50 3.14 0.0167 0.42 2.16 0.0889
9p 422 0.15 -0.484 0.978 0.35 1.47 0.203
9q 1113 0.00 -1.52 0.978 0.37 2.46 0.0463
10p 409 0.18 -0.332 0.978 0.12 -0.828 0.884
10q 1268 0.00 -1.73 0.978 0.11 -0.55 0.884
11p 862 0.25 0.75 0.978 0.20 0.221 0.688
11q 1515 0.19 0.636 0.978 0.19 0.636 0.515
12p 575 0.15 -0.398 0.978 0.35 1.6 0.203
12q 1447 0.19 0.572 0.978 0.19 0.572 0.515
13q 654 0.09 -0.854 0.978 0.44 2.71 0.0335
14q 1341 0.00 -1.6 0.978 0.21 0.806 0.467
15q 1355 0.00 -1.54 0.978 0.26 1.47 0.203
16p 872 0.56 2.97 0.02 0.71 5.26 1.47e-06
16q 702 0.00 -1.18 0.978 0.68 5.51 7.19e-07
17p 683 0.00 -1.61 0.978 0.42 2.56 0.0419
17q 1592 0.12 -0.0382 0.978 0.18 0.595 0.515
18p 143 0.23 0.0284 0.978 0.38 1.41 0.212
18q 446 0.14 -0.59 0.978 0.29 0.89 0.44
19p 995 0.12 -0.471 0.978 0.18 0.0811 0.748
19q 1709 0.12 0.0594 0.978 0.18 0.714 0.5
20p 355 0.39 1.82 0.341 0.08 -1.1 0.886
20q 753 0.33 1.61 0.429 0.08 -1.01 0.886
21q 509 0.12 -0.87 0.978 0.12 -0.87 0.884
22q 921 0.00 -1.66 0.978 0.32 1.63 0.203
Xq 1312 0.21 0.706 0.978 0.31 1.86 0.156
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/BRCA-TP/8143030/segmentationfile.txt

  • Markers File = /xchip/cga/gdac-prod/tcga-gdac/jobResults/PrepareGisticDNASeq/BRCA-TP/8143030/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 19 Input Tumor Samples.

Tumor Sample Names
TCGA-A2-A0EU-01A-22D-A060-02
TCGA-A7-A0D9-01A-31D-A060-02
TCGA-AO-A0JF-01A-11D-A060-02
TCGA-AO-A0JJ-01A-11D-A060-02
TCGA-AO-A0JL-01A-11D-A060-02
TCGA-AR-A0TU-01A-31D-A106-02
TCGA-B6-A0RE-01A-11D-A060-02
TCGA-B6-A0RG-01A-11D-A060-02
TCGA-B6-A0RI-01A-11D-A060-02
TCGA-B6-A0X4-01A-11D-A106-02

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)