Genome-wide profiling of oral squamous cell carcinoma by array-based comparative genomic hybridization.
OBJECTIVE
Array-based comparative genomic hybridization (aCGH) was used to develop a genome-wide molecular profile of oral squamous cell carcinoma (OSCC). Copy number alterations (CNAs) were identified by chromosomal region, mapped to specific genes, and compared with several previously documented CNAs associated with head and neck squamous cell carcinoma (HNSCC). The status of 512 commonly altered cancer genes was assessed and evaluated as potential correlates of tumor behavior.


METHODS
Tumor tissue DNA was isolated for aCGH from 21 prospectively collected fresh-frozen OSCC specimens. aCGH was performed at 0.9-Mb resolution to identify distinct regions of genomic alteration and their associated genes. Cancer genes commonly altered were then correlated with clinicopathologic tumor data.


RESULTS
Genomic regions most frequently amplified (>35%) were located on 3q, 5p, 8q, 9q, and 20q, although regions most frequently deleted (>40%) involved chromosomes 3p, 8p, 13q, and 18q. Minimal regions of CNA identified, by aCGH narrowed larger, previously documented CNAs associated with HNSCC to significantly smaller regions, yielding shorter lists of candidate genes. Cancer-related genes altered in greater than 25% OSCC samples were identified (22 amplified, 17 deleted). Several genes associated with the Fanconi anemia DNA-damage response pathway were frequently altered, including BRCA1, BRCA2, FANCD2, and FANCG. Other cancer-related genes linked to hereditary cancer syndromes include VHL, MLH1, XPC, and RB1.


CONCLUSIONS
Genome-wide aCGH can be used to detect and map CNAs in OSCC tissue specimens with high resolution. These data implicate several candidate genes and gene pathways in the tumorigenesis of sporadic OSCC.
Sparano
Anthony
A
Department of Otorhinolaryngology, Head and Neck, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Quesnelle
Kelly M
KM
Kumar
Madhu S
MS
Wang
Yan
Y
Sylvester
Albert J
AJ
Feldman
Michael
M
Sewell
Duane A
DA
Weinstein
Gregory S
GS
Brose
Marcia S
MS
D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D002869:Chromosome Aberrations / Q000706:statistics & numerical data; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D052138:Genes, Neoplasm; D020022:Genetic Predisposition to Disease; D016678:Genome; D006801:Humans; D008297:Male; D009062:Mouth Neoplasms / Q000235:genetics* / Q000473:pathology; D009693:Nucleic Acid Hybridization; D009857:Oncogenes / Q000235:genetics*; D011446:Prospective Studies; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D046509:Tissue Culture Techniques
D004273:DNA, Neoplasm