May 2011
Volume 52, Issue 6
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Clinical Trials  |   May 2011
Genomic Identification of Significant Targets in Ciliochoroidal Melanoma
Author Affiliations & Notes
  • Tara A. McCannel
    From the Department of Ophthalmology, University of California, Los Angeles, The Jules Stein Eye Institute, Los Angeles, California; and
  • Barry L. Burgess
    From the Department of Ophthalmology, University of California, Los Angeles, The Jules Stein Eye Institute, Los Angeles, California; and
  • Stanley F. Nelson
    the Department of Human Genetics, University of California, Los Angeles, Los Angeles, California.
  • Ascia Eskin
    the Department of Human Genetics, University of California, Los Angeles, Los Angeles, California.
  • Bradley R. Straatsma
    From the Department of Ophthalmology, University of California, Los Angeles, The Jules Stein Eye Institute, Los Angeles, California; and
  • Corresponding author: Tara A. McCannel, The Jules Stein Eye Institute, 100 Stein Plaza, Los Angeles, CA 90095; [email protected]
Investigative Ophthalmology & Visual Science May 2011, Vol.52, 3018-3022. doi:https://doi.org/10.1167/iovs.10-5864
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      Tara A. McCannel, Barry L. Burgess, Stanley F. Nelson, Ascia Eskin, Bradley R. Straatsma; Genomic Identification of Significant Targets in Ciliochoroidal Melanoma. Invest. Ophthalmol. Vis. Sci. 2011;52(6):3018-3022. https://doi.org/10.1167/iovs.10-5864.

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Abstract

Purpose.: To identify genomic targets for ciliochoroidal melanoma diagnosis, prognosis, and therapy.

Methods.: Fifty-eight ciliochoroidal melanomas were analyzed by high-resolution, genome-wide, single nucleotide polymorphism (SNP) mapping arrays. The 58 SNP arrays were compared to 48 HapMap normals representing both sexes and assessed with a systematic statistical method, Genomic Identification of Significant Targets in Cancer (GISTIC), to identify significant ciliochoroidal chromosomal abnormalities including chromosome-arm–sized as well as focal events of amplification and deletion. The 58 SNP arrays were also analyzed to assess copy number.

Results.: The 58 ciliochoroidal melanomas analyzed by GISTIC showed large regions of chromosome amplification on 6p and 8q in addition to focal amplification peaks on 1q31.3, 4p16.2, 9p23, and 9q33.1. The melanomas also showed large regions of deletion on 1p and all of 3, 6q, 8p, and 16q, as well as focal deletion peaks on 2p12, 2q14.3, 4q26, 5q21.1, 7q21.11, 8p21.3, 9p21.1, 13q21.31, 13q31.3, and 16q23.3. For each large region and focal peak, the statistical significance was computed, and known genes were specified.

Conclusions.: High-resolution analysis of ciliochoroidal melanoma cytogenetic aberration patterns supports the utility of systematic characterization of the cancer genome by corroborating known melanoma-related genomic aberrations and identifying additional melanoma-related genomic abnormalities that can be used to identify potential targets for diagnosis, prognosis and therapy. (ClinicalTrials.gov number, NCT00344799.)

Comprehensive knowledge of the genomic alterations responsible for cancer is the foundation for understanding tumor biology, developing diagnostics, assessing prognosis, and formulating targeted therapeutics. Elucidation of the human genome and availability of high-resolution, genome-wide DNA arrays have prompted development of statistical methods to assess chromosomal abnormalities associated with cancer. 1 4  
Beroukhim et al. 3 developed a statistical method for analysis of chromosomal aberrations, called Genomic Identification of Significant Targets in Cancer (GISTIC), that identifies aberrations more likely to promote or drive” cancer pathogenesis. With analysis of a set of high-resolution, whole-genome DNA arrays from a specific type of cancer, GISTIC identifies regions of the genome that are aberrant more often than would be expected by chance, with greater weight given to high-amplitude events (for example, high-level copy number gains or homozygous deletions) that are less likely to be random. 
In GISTIC, each genomic aberration is assigned a G-score that considers the amplitude of the aberration and the frequency of occurrence in a set of samples. 3,5 False-discovery rate q-values are then calculated for the aberrant regions, and regions with q-values below a user-defined threshold are considered significant. 
For each significant region of aberration, a peak region is determined, which is the part of the region with the greatest amplitude and frequency of aberration. Moreover, a wide peak is established by using a leave-one-out algorithm to allow for errors in the boundaries for a single sample. Each significant aberrant region is also tested to determine whether it results primarily from broad events (longer than half a chromosome arm), focal events, or significant levels of both. With this methodology, GISTIC outputs the genomic location and calculated q-value for the aberrant regions, identifies the samples that exhibit each significant amplification or deletion, and lists the known genes located in each wide peak region. 3 5  
GISTIC has been applied to sets of high-resolution, genome-wide DNA arrays to identify cancer oncogenes and suppressor genes in a range of cancers including breast cancer, 2 colorectal cancer, 2 glioma, 3 B-cell lymphoma, 4 and lung adenocarcinoma. 6 We report the application of GISTIC to identification of cancer-related genes (oncogenes and suppressor genes) in ciliochoroidal melanoma. 
Materials and Methods
In 58 eyes of 58 patients with a clinical diagnosis of ciliochoroidal melanoma (melanoma arising from the choroid and/or the ciliary body), transscleral fine needle aspiration biopsy (FNAB) was performed immediately before iodine-125 plaque placement (53 eyes) or immediately (<5 minutes) after enucleation (five eyes). Biopsy material was analyzed for cytopathology, cytogenetic characteristics, and gene expression profiles and prepared for cell culture. 7 9  
This research was approved by the Institutional Review Board of the University of California, Los Angeles (UCLA), and work was in compliance with the Health Insurance Portability and Accountability Act of 1996 (HIPAA). The research also adhered to the tenets of the Declaration of Helsinki. Before treatment, evaluation of each patient included comprehensive ophthalmic examination, ultrasonography, photography, optical coherence tomography, and fluorescein angiography. All patients had systemic evaluation, usually by an oncologist at the Jonsson Comprehensive Cancer Center, which showed no clinical evidence of ciliochoroidal melanoma metastasis or other cancer. In addition, patients were offered psychologic support by a clinical psychologist or social worker with particular expertise in ciliochoroidal melanoma. 10  
Isolation of DNA for Microarray Analysis and Single-Nucleotide Polymorphism Analysis
Pooled FNAB aspirates were stabilized (RNAprotect Cell Reagent; Qiagen, Valencia, CA) and pelleted, and DNA and RNA were simultaneously isolated from the same sample (AllPrep DNA/RNA Mini Kit; Qiagen), per the manufacturer's instructions. Isolated DNA was quantified (model ND-1000; NanoDrop, Wilmington, DE). No DNA sample was subjected to whole-genome amplification techniques. The DNA copy number was assessed by using high-resolution, genome-wide single nucleotide polymorphism (SNP) gene mapping arrays (250k NSPI; Affymetrix, Santa Clara, CA). Probe preparation, hybridization, and reading were performed by the UCLA DNA Microarray Facility within the Jonsson Comprehensive Cancer Center Gene Expression Shared Resource in accordance with standard manufacturer's protocols. Copy number variation was computed with allied software (Genotyping Console 4.0; Affymetrix). 
GISTIC Analysis
The 58 ciliochoroidal melanomas assessed for chromosomal aberrations by the mapping arrays and quantitated (Genotyping Console 4.0; Affymetrix) were analyzed by using GISTIC to identify significant ciliochoroidal melanoma cytogenetic aberrations, including broad and focal events of amplification and deletion. 3,5  
Briefly, aberrations were assigned a G-score that considered the amplitude of the aberration as well as the frequency of its occurrence across samples. False-discovery rate q-values were calculated for aberrant regions, and q-values below the default threshold were considered significant. For each significant region, a peak region was identified, which represented part of the aberrant region with greatest amplitude and frequency of alteration. In addition, a wide peak was identified using a leave-one-out algorithm. Each significantly aberrant region was tested to determine whether it resulted primarily from a broad event (longer than half a chromosome arm), a focal event, or significant levels of both. The statistical module reported the genomic locations and calculated q-values for the aberrant regions. In addition, the module identified the samples that exhibited each significant amplification or deletion and listed known genes located in each wide peak and peak region. 
For GISTIC analysis, CEL files were analyzed with GenePattern from the Broad Institute (Massachusetts Institute of Technology, Cambridge, MA). First, the CEL files were submitted to SNPFileCreator, where PM/MM Difference Model (dChipSNP) 11 modeling was used. Next, the 58 CEL files were compared to 48 normal HapMap (www.hapmap.org) CEL files with CopyNumberDivideByNormals. The copy number data were then segmented by using GLAD (Gain and Loss Analysis of DNA). 12 Last, segmented copy number data were analyzed with GISTIC by using the Human Genome of May 2004 (build hg17) and default parameters. 
In dChipSNP, the arrays were normalized by invariant set normalization, and signal intensities were computed using 48 HapMap samples as a normal reference. The arrays were then genotyped (BRLMM Analysis Tool; Genotyping Console 4.0; Affymetrix). Copy number was inferred by using median smoothing. 
Results
GISTIC analysis of 58 ciliochoroidal melanoma samples showed statistically significant large regions and focal peaks of chromosome amplification and deletion. Broad regions of amplification were identified on 6p and 8q; focal amplification peaks were shown on 1q31.3, 4p16.2, 9p23, and 9q33.1 (Fig. 1B). Genes known to be present in the large regions and the focal peaks of amplification are listed in Table 1. Unknown genes were also likely to be within the regions and peaks of amplification. 
Figure 1.
 
(A) Global chromosomal gain and loss data of 58 ciliochoroidal melanomas inferred from Log2 ratios by dChipSNP. 11 Red: regions of gain; blue: regions of loss. Log2ratios are inferred by the median-smoothing method in dChipSNP. (B, C) GISTIC analysis of aberrations as well as the frequency of its occurrence across samples. Amplifications are shown in (B) as red peaks and deletions are shown in (C) as blue peaks. False-discovery rate q-values, at the bottom of the figures, are significant for values < 0.25 (represented as a vertical green line). Right: the peak region or significant gene(s) corresponding to the greatest amplitude in each locus. Left: broad and focal regions of amplification and deletion. Chromosomes 1 through 22 are identified on the left and horizontal dotted lines represent the location of the centromeres. G-scores at the top weigh the amplitude of aberration as well as the frequency of its occurrence across samples.
Figure 1.
 
(A) Global chromosomal gain and loss data of 58 ciliochoroidal melanomas inferred from Log2 ratios by dChipSNP. 11 Red: regions of gain; blue: regions of loss. Log2ratios are inferred by the median-smoothing method in dChipSNP. (B, C) GISTIC analysis of aberrations as well as the frequency of its occurrence across samples. Amplifications are shown in (B) as red peaks and deletions are shown in (C) as blue peaks. False-discovery rate q-values, at the bottom of the figures, are significant for values < 0.25 (represented as a vertical green line). Right: the peak region or significant gene(s) corresponding to the greatest amplitude in each locus. Left: broad and focal regions of amplification and deletion. Chromosomes 1 through 22 are identified on the left and horizontal dotted lines represent the location of the centromeres. G-scores at the top weigh the amplitude of aberration as well as the frequency of its occurrence across samples.
Table 1.
 
Description of the Six Regions of Amplification Identified by GISTIC
Table 1.
 
Description of the Six Regions of Amplification Identified by GISTIC
Chromosome Region, Location,* and Peak Width
1q31.3 4p16.2 6p24.3 8q24.13 9p23 9q33.1
Chr1: 182188599–196365692 Chr4: 1–9443448 Chr6: 5869500–11661049 Chr8: 122244031–123530468 Chr9: 11064234–11087561 Chr9: 116949236–116981194
14.18 mb 9.44 mb 5.79 mb 1.29 mb 23.3 kb 32.0 kb
F13B GLRX2 ADD1 C4orf8 TMEM175 BMP6 HAS2 [PTPRD] ASTN2
CFH UCHL5 ADRA2C KIAA0232 ABLIM2 DSP
CFHR1 FLJ20054 ATP5I C4orf6 TMEM128 F13A1
CFHR2 C1orf27 CRMP1 TETRAN MGC21675 GCNT2
PDC LHX9 CTBP1 MAEA TMEM129 MAK
PLA2G4A RGS18 DGKQ PCGF3 MRFAP1 NEDD9
PTGS2 CDC73 EVC SPON2 HTRA3 RREB1
PTPRC CFHR5 FGFR3 TACC3 MRFAP1L1 SSR1
RGS1 HMCN1 GAK MXD4 EVC2 TFAP2A
RGS2 ATP6V1G3 GRK4 CPLX1 OTOP1 GCM2
RGS13 NEK7 HD SLC26A1 ZNF595 LY86
TROVE2 DENND1B HGFAC MAN2B2 JAKMIP1 EEF1E1
TPR ASPM IDUA D4S234E FAM53A SLC35B3
B3GALT2 C1orf99 LETM1 GPR78 C4orf23 NRN1
PRG4 FAM5C LRPAP1 STX18 ZNF509 TMEM14C
CFHR4 KCNT2 MSX1 FGFRL1 ZNF721 ELOVL2
CFHR3 ZBTB41 MYL5 CYTL1 ZNF718 PAK1IP1
OCLM C1orf53 PDE6B SH3TC1 CCDC96 MUTED
CRB1 RGS21 PPP2R2C PIGG CRIPAK TXNDC5
RGS12 CNO DOK7 TMEM14B
RNF4 STK32B RNF212 RIOK1
S100P LYAR NAT8L C6orf151
SH3BP2 TBC1D14 LOC345222 NO145
WFS1 SORCS2 POLN C6orf218
WHSC1 KIAA1530 DUB3 OFCC1
WHSC2 ZFYVE28 FLJ46481 CAGE1
ZNF141 AFAP LOC389199 HERVFRD
SLBP TNIP2 FLJ45966
ACOX3 C4orf15 DEFB131
CPZ GRPEL1 LOC650293
C4orf9 MFSD7
Deletions of large regions were identified on 1p, all of 3, 6q, 8p, 16q; focal deletion peaks were shown on 2p12, 2q14.3, 4q26, 5q21.1, 7q21.11, 8p21.3, 9p21.1, 13q21.31, 13q31.3, and 16q23.3 (Fig. 1C). Genes known to be present in the large regions and focal peaks of deletion were identified (Table 2). In all likelihood, unknown genes were also located in the deleted regions and peaks. 
Table 2.
 
Description of 13 Regions of Deletion Identified by GISTIC
Table 2.
 
Description of 13 Regions of Deletion Identified by GISTIC
Chromosome Region, Location,* and Peak Width
1p31.2 2p12 2q14.3 3p14.3 4q26 5q21.1 6q16.1
Chr1: 66658328–66691989 Chr2: 81577056–81593777 Chr2: 123770089–123806320 Chr3: 20894925–55444658 Chr4: 97140936–118241698 Chr5: 100747054–100797923 Chr6: 96489300–96528053
33.7 kb 16.7 kb 36.2 kb 34.55 mb 21.10 mb 50.9 kb 38.8 kb
[SGIP1] [CTNNA2] [CNTNAP5] 288 genes from ZNF659 through CACNA2D3 83 genes from MGC46496 through UGT8 [ST8SIA4] [FUT9]
Chromosome Region, Location,* and Peak Width
7q21.11 8p21.3 8p23.1 9p21.1 13q21.31 13q31.3 16q23.3
Chr7: 83836878–83863047 Chr8: 19408244–35523310 Chr8: 5834549–6092262 Chr9: 29394373–29403193 Chr13: 64467750–64470216 Chr13: 93289062–93317950 Chr16: 82446130–88827254
26.2 kb 16.12 mb 258 kb 8.8 kb 2.5 kb 28.9 kb 6.38 mb
[SEMA3A] 96 genes from ChGn through RNF122 [MCPH1] [LRRN6C] [PCDH9] GPC6 80 genes from OSGIN1 through PRDM7 (telomere)
Discussion
Somatic mutations in the DNA of tumor cells underlie most cancers and are of fundamental importance in understanding the biology of ciliochoroidal melanoma. Thus, we used high-resolution, genome-wide arrays to characterize DNA in 58 choroidal melanomas and used GISTIC analysis of the 58 samples to elucidate large regions and focal peaks of DNA amplification and deletion. Only with systematic statistical assessment of a reasonably large group of samples is the presence and frequency of recurrent genomic aberrations evident. GISTIC is of particular value in identifying narrow regions and focal peaks of amplification and deletion that are not apparent in study of single samples or small clusters of samples. 
In addition to identifying the aberrations, a further challenge is to distinguish between cancer promoter or driver mutations that are functionally important (that is, mutations that confer a biological advantage that enables the tumor to initiate, grow, persist, or metastasize) and passenger mutations that are antecedent or random events that carry no propensity for growth or tumor formation. Although the GISTIC methodology is more likely to identify driver mutations that recur because of affirmative selection during tumor evolution, GISTIC may identify passenger mutations based on biases in DNA mutation or repair processes. 3  
Emphasizing the tendency of GISTIC to identify driver genes is recognition of deletions of all of 3,and of 1p, 6q, 8p, and 16q, together with chromosomal amplification of 6p and 8q. These regional amplifications and deletions have been generally associated with metastasis in our integrative analysis of ciliochoroidal melanomas 9 and identified in other analyses of uveal melanomas as associated with an unfavorable prognosis for metastasis. 13 18 Illustrating this corroboration, Trolet et al. 18 studied cytogenetic factors associated with uveal melanoma metastasis and showed that the best rate of correlation for uveal melanoma metastasis with a set of five regions combined: gains of 6p and 8q and losses of all of 3 and of 8p and 16q. All five of these chromosomal regions, as well as additional regions and focal peaks, were identified as significant genomic aberrations by GISTIC. 
Further illustrating the potential value of GISTIC is focal regions of aberration identified on 8p, 13q, and 16q. During a review of reports that examined chromosomal instability in uveal melanomas, we found that Onken et al. 19 had identified LZTS1 through an analysis of 12 SNPs in 8p. They reported the identification of a region of deletion and hypermethylation at 8p12-8p22, encompassing the LZTS1 locus. Against the broad background of 8p loss, our global GISTIC analysis similarly defined a focal region of deletion centered on 8p21.3, which included the LZTS1 locus. Among the 58 samples, the highest frequency of deletion on chromosome 8 occurs at p23.2 in a 258-kb region where no known genes exist. This deletion was identified in 20 (35%) of the samples and encompasses bases 5,834,549-6,092,262. 
Two regions of significant focal deletion were identified on chromosome 13 at q21.31 and q31.3. The former occurred in a 10-kb region a containing no known genes and the latter was a specific 28.9-kb deletion centered within the glypican 6 (GPC6) gene. GPC6 is a cell surface heparan sulfate proteoglycan with wide expression in adult tissues. Lau et al. 20 identified this gene as a potential tumor suppressor in Chinese sporadic retinoblastoma patients with nonrandom allelic loss of heterozygosity at 13q31. 20 Preliminary investigation of the expression of this gene in our ciliochoroidal melanomas has failed to detect its transcription; this warrants further examination. 
Perhaps the most intriguing deletions indentified by GISTIC were those found in the telomeric region of 16q. Copy number analysis found that seven samples had near complete loss of the 16q arm. GISTIC corroborated that finding and identified a further nine samples that had focal deletion of the telomeric 6.38-mb region of 16q. Significantly, the deletion of highest frequency commences at the locus of oxidative stress–induced growth inhibitor 1 (OSGIN1 or, alternatively, OKL38). Three different studies have identified this gene as a negative regulator of cell growth, as having a proapoptotic function, and have shown that its downregulation may lead to tumorigenesis or progression of a number of different carcinomas. 21 23 Loss of heterozygosity of the telomeric region of 16q is significant for other genes that have been shown to be involved in the progression of melanocytic lesions including melanocortin-1 receptor (MC1R). 
Of distinct relevance is the clinical course of patients who were the sources of the ciliochoroidal melanoma biopsy samples in this report. Within 2 years of primary melanoma treatment, 6 of 58 patients developed clinical evidence of melanoma metastasis. Of those six patients, four had the deletion of 16q identified by GISTIC. 
Strengths of this report relate to the cohort of 58 ciliochoroidal melanomas evaluated in a uniform manner with high-resolution, genome-wide DNA arrays and gene microarrays and application, for the first time to our knowledge, of GISTIC to ciliochoroidal melanoma. Although all samples were obtained through fine-needle aspiration biopsy of primary tumors, heterogeneity was not a relevant factor to GISTIC as used, because GISTIC was performed to identify focal amplifications or deletions on all samples irrespective of the primary chromosomal aberration. Limitations must consider the possible failure of the GISTIC methodology to detect rare cancer-promoter genes and the likelihood that GISTIC methodology selects passenger genes as well as driver genes. Overall, chromosomal copy number aberrations are only one part of the full spectrum of cytogenetic, gene expression and epigenetic events that contribute to choroidal melanoma and melanoma metastasis. Other parts of this complex process must be assessed to advance knowledge regarding ciliochoroidal melanoma. 
In summary, we report a series of ciliochoroidal melanoma biopsy samples evaluated for chromosomal aberrations by high-resolution, genome-wide DNA array as well as microarrays and analyzed by the statistical procedures of GISTIC. The analysis identified cytogenetic aberrations of amplification and deletion that warrant study as potential targets for ciliochoroidal melanoma diagnosis, prognosis, and therapy. 
Footnotes
 Supported by the George and Ruth E. Moss Trust, the American Association of Cancer Research, and an unrestricted grant from Research to Prevent Blindness.
Footnotes
 Disclosure: T.A. McCannel, None; B.L. Burgess, None; S.F. Nelson, None; A. Eskin, None; B.R. Straatsma, None
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Figure 1.
 
(A) Global chromosomal gain and loss data of 58 ciliochoroidal melanomas inferred from Log2 ratios by dChipSNP. 11 Red: regions of gain; blue: regions of loss. Log2ratios are inferred by the median-smoothing method in dChipSNP. (B, C) GISTIC analysis of aberrations as well as the frequency of its occurrence across samples. Amplifications are shown in (B) as red peaks and deletions are shown in (C) as blue peaks. False-discovery rate q-values, at the bottom of the figures, are significant for values < 0.25 (represented as a vertical green line). Right: the peak region or significant gene(s) corresponding to the greatest amplitude in each locus. Left: broad and focal regions of amplification and deletion. Chromosomes 1 through 22 are identified on the left and horizontal dotted lines represent the location of the centromeres. G-scores at the top weigh the amplitude of aberration as well as the frequency of its occurrence across samples.
Figure 1.
 
(A) Global chromosomal gain and loss data of 58 ciliochoroidal melanomas inferred from Log2 ratios by dChipSNP. 11 Red: regions of gain; blue: regions of loss. Log2ratios are inferred by the median-smoothing method in dChipSNP. (B, C) GISTIC analysis of aberrations as well as the frequency of its occurrence across samples. Amplifications are shown in (B) as red peaks and deletions are shown in (C) as blue peaks. False-discovery rate q-values, at the bottom of the figures, are significant for values < 0.25 (represented as a vertical green line). Right: the peak region or significant gene(s) corresponding to the greatest amplitude in each locus. Left: broad and focal regions of amplification and deletion. Chromosomes 1 through 22 are identified on the left and horizontal dotted lines represent the location of the centromeres. G-scores at the top weigh the amplitude of aberration as well as the frequency of its occurrence across samples.
Table 1.
 
Description of the Six Regions of Amplification Identified by GISTIC
Table 1.
 
Description of the Six Regions of Amplification Identified by GISTIC
Chromosome Region, Location,* and Peak Width
1q31.3 4p16.2 6p24.3 8q24.13 9p23 9q33.1
Chr1: 182188599–196365692 Chr4: 1–9443448 Chr6: 5869500–11661049 Chr8: 122244031–123530468 Chr9: 11064234–11087561 Chr9: 116949236–116981194
14.18 mb 9.44 mb 5.79 mb 1.29 mb 23.3 kb 32.0 kb
F13B GLRX2 ADD1 C4orf8 TMEM175 BMP6 HAS2 [PTPRD] ASTN2
CFH UCHL5 ADRA2C KIAA0232 ABLIM2 DSP
CFHR1 FLJ20054 ATP5I C4orf6 TMEM128 F13A1
CFHR2 C1orf27 CRMP1 TETRAN MGC21675 GCNT2
PDC LHX9 CTBP1 MAEA TMEM129 MAK
PLA2G4A RGS18 DGKQ PCGF3 MRFAP1 NEDD9
PTGS2 CDC73 EVC SPON2 HTRA3 RREB1
PTPRC CFHR5 FGFR3 TACC3 MRFAP1L1 SSR1
RGS1 HMCN1 GAK MXD4 EVC2 TFAP2A
RGS2 ATP6V1G3 GRK4 CPLX1 OTOP1 GCM2
RGS13 NEK7 HD SLC26A1 ZNF595 LY86
TROVE2 DENND1B HGFAC MAN2B2 JAKMIP1 EEF1E1
TPR ASPM IDUA D4S234E FAM53A SLC35B3
B3GALT2 C1orf99 LETM1 GPR78 C4orf23 NRN1
PRG4 FAM5C LRPAP1 STX18 ZNF509 TMEM14C
CFHR4 KCNT2 MSX1 FGFRL1 ZNF721 ELOVL2
CFHR3 ZBTB41 MYL5 CYTL1 ZNF718 PAK1IP1
OCLM C1orf53 PDE6B SH3TC1 CCDC96 MUTED
CRB1 RGS21 PPP2R2C PIGG CRIPAK TXNDC5
RGS12 CNO DOK7 TMEM14B
RNF4 STK32B RNF212 RIOK1
S100P LYAR NAT8L C6orf151
SH3BP2 TBC1D14 LOC345222 NO145
WFS1 SORCS2 POLN C6orf218
WHSC1 KIAA1530 DUB3 OFCC1
WHSC2 ZFYVE28 FLJ46481 CAGE1
ZNF141 AFAP LOC389199 HERVFRD
SLBP TNIP2 FLJ45966
ACOX3 C4orf15 DEFB131
CPZ GRPEL1 LOC650293
C4orf9 MFSD7
Table 2.
 
Description of 13 Regions of Deletion Identified by GISTIC
Table 2.
 
Description of 13 Regions of Deletion Identified by GISTIC
Chromosome Region, Location,* and Peak Width
1p31.2 2p12 2q14.3 3p14.3 4q26 5q21.1 6q16.1
Chr1: 66658328–66691989 Chr2: 81577056–81593777 Chr2: 123770089–123806320 Chr3: 20894925–55444658 Chr4: 97140936–118241698 Chr5: 100747054–100797923 Chr6: 96489300–96528053
33.7 kb 16.7 kb 36.2 kb 34.55 mb 21.10 mb 50.9 kb 38.8 kb
[SGIP1] [CTNNA2] [CNTNAP5] 288 genes from ZNF659 through CACNA2D3 83 genes from MGC46496 through UGT8 [ST8SIA4] [FUT9]
Chromosome Region, Location,* and Peak Width
7q21.11 8p21.3 8p23.1 9p21.1 13q21.31 13q31.3 16q23.3
Chr7: 83836878–83863047 Chr8: 19408244–35523310 Chr8: 5834549–6092262 Chr9: 29394373–29403193 Chr13: 64467750–64470216 Chr13: 93289062–93317950 Chr16: 82446130–88827254
26.2 kb 16.12 mb 258 kb 8.8 kb 2.5 kb 28.9 kb 6.38 mb
[SEMA3A] 96 genes from ChGn through RNF122 [MCPH1] [LRRN6C] [PCDH9] GPC6 80 genes from OSGIN1 through PRDM7 (telomere)
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