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. 2006 Nov 29:7:299.
doi: 10.1186/1471-2164-7-299.

Genome-wide loss of heterozygosity and copy number alteration in esophageal squamous cell carcinoma using the Affymetrix GeneChip Mapping 10 K array

Nan Hu  1 , Chaoyu Wang, Ying Hu, Howard H Yang, Li-Hui Kong, Ning Lu, Hua Su, Quan-Hong Wang, Alisa M Goldstein, Kenneth H Buetow, Michael R Emmert-Buck, Philip R Taylor, Maxwell P Lee
Affiliations

Genome-wide loss of heterozygosity and copy number alteration in esophageal squamous cell carcinoma using the Affymetrix GeneChip Mapping 10 K array

Nan Hu et al. BMC Genomics. .

Abstract

Background: Esophageal squamous cell carcinoma (ESCC) is a common malignancy worldwide. Comprehensive genomic characterization of ESCC will further our understanding of the carcinogenesis process in this disease.

Results: Genome-wide detection of chromosomal changes was performed using the Affymetrix GeneChip 10 K single nucleotide polymorphism (SNP) array, including loss of heterozygosity (LOH) and copy number alterations (CNA), for 26 pairs of matched germ-line and micro-dissected tumor DNA samples. LOH regions were identified by two methods--using Affymetrix's genotype call software and using Affymetrix's copy number alteration tool (CNAT) software--and both approaches yielded similar results. Non-random LOH regions were found on 10 chromosomal arms (in decreasing order of frequency: 17p, 9p, 9q, 13q, 17q, 4q, 4p, 3p, 15q, and 5q), including 20 novel LOH regions (10 kb to 4.26 Mb). Fifteen CNA-loss regions (200 kb to 4.3 Mb) and 36 CNA-gain regions (200 kb to 9.3 Mb) were also identified.

Conclusion: These studies demonstrate that the Affymetrix 10 K SNP chip is a valid platform to integrate analyses of LOH and CNA. The comprehensive knowledge gained from this analysis will enable improved strategies to prevent, diagnose, and treat ESCC.

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Figures

Figure 1
Figure 1
Chromosome 9. Each column in the picture represents an individual case and shows genotyping in germ-line DNA and matched micro-dissected tumor; LOH is shown in red, retention in blue, and homozygous or "no call" in grey. B indicates blood DNA and T indicates tumor DNA (from matched, micro-dissected sample). To the left of the picture, columns show (from left to right): microsatellite markers, cartoon of the chromosome, and SNPs examined in the 10 K SNP chip. To the right of the picture, red bars show deletion regions (as defined from our conservative "LOH/Model A"), blue bars show regions with CNA losses (from CNAT), and green bars show regions with CNA gains (from CNAT).
Figure 2
Figure 2
Chromosome 13. Each column in the picture represents an individual case and shows genotyping in germ-line DNA and matched micro-dissected tumor; LOH is shown in red, retention in blue, and homozygous or "no call" in grey. B indicates blood DNA and T indicates tumor DNA (from matched, micro-dissected sample). To the left of the picture, columns show (from left to right): microsatellite markers, cartoon of the chromosome, and SNPs examined in the 10 K SNP chip. To the right of the picture, red bars show deletion regions (as defined from our conservative "LOH/Model A"), blue bars show regions with CNA losses (from CNAT), and green bars show regions with CNA gains (from CNAT).
Figure 3
Figure 3
Chromosome 17. Each column in the picture represents an individual case and shows genotyping in germ-line DNA and matched micro-dissected tumor; LOH is shown in red, retention in blue, and homozygous or "no call" in grey. B indicates blood DNA and T indicates tumor DNA (from matched, micro-dissected sample). To the left of the picture, columns show (from left to right): microsatellite markers, cartoon of the chromosome, and SNPs examined in the 10 K SNP chip. To the right of the picture, red bars show deletion regions (as defined from our conservative "LOH/Model A"), blue bars show regions with CNA losses (from CNAT), and green bars show regions with CNA gains (from CNAT).
Figure 4
Figure 4
Chromosome 3. Each column in the picture represents an individual case and shows genotyping in germ-line DNA and matched micro-dissected tumor; LOH is shown in red, retention in blue, and homozygous or "no call" in grey. B indicates blood DNA and T indicates tumor DNA (from matched, micro-dissected sample). To the left of the picture, columns show (from left to right): microsatellite markers, cartoon of the chromosome, and SNPs examined in the 10 K SNP chip. To the right of the picture, red bars show deletion regions (as defined from our conservative "LOH/Model A"), blue bars show regions with CNA losses (from CNAT), and green bars show regions with CNA gains (from CNAT).
Figure 5
Figure 5
Chromosome 7. Each column in the picture represents an individual case and shows genotyping in germ-line DNA and matched micro-dissected tumor; LOH is shown in red, retention in blue, and homozygous or "no call" in grey. B indicates blood DNA and T indicates tumor DNA (from matched, micro-dissected sample). To the left of the picture, columns show (from left to right): microsatellite markers, cartoon of the chromosome, and SNPs examined in the 10 K SNP chip. To the right of the picture, red bars show deletion regions (as defined from our conservative "LOH/Model A"), blue bars show regions with CNA losses (from CNAT), and green bars show regions with CNA gains (from CNAT).
Figure 6
Figure 6
Chromosome 8. Each column in the picture represents an individual case and shows genotyping in germ-line DNA and matched micro-dissected tumor; LOH is shown in red, retention in blue, and homozygous or "no call" in grey. B indicates blood DNA and T indicates tumor DNA (from matched, micro-dissected sample). To the left of the picture, columns show (from left to right): microsatellite markers, cartoon of the chromosome, and SNPs examined in the 10 K SNP chip. To the right of the picture, red bars show deletion regions (as defined from our conservative "LOH/Model A"), blue bars show regions with CNA losses (from CNAT), and green bars show regions with CNA gains (from CNAT).
Figure 7
Figure 7
Comparison of SNPs with cLOH (from our less conservative "cLOH/Model B") and CNAs (from CNAT software using pooled DNA from normal controls).
See this image and copyright information in PMC

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