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


CONCLUSIONS
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.
Hu
Nan
N
Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, NCI, USA. nh38k@nih.gov <nh38k@nih.gov>
Wang
Chaoyu
C
Hu
Ying
Y
Yang
Howard H
HH
Kong
Li-Hui
LH
Lu
Ning
N
Su
Hua
H
Wang
Quan-Hong
QH
Goldstein
Alisa M
AM
Buetow
Kenneth H
KH
Emmert-Buck
Michael R
MR
Taylor
Philip R
PR
Lee
Maxwell P
MP
D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D002869:Chromosome Aberrations; D002874:Chromosome Mapping / Q000379:methods; D002877:Chromosomes, Human; D004938:Esophageal Neoplasms / Q000235:genetics*; D005260:Female; D018628:Gene Dosage / Q000502:physiology*; D015894:Genome, Human; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D020641:Polymorphism, Single Nucleotide