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Genome‐Wide Profiling of Oral Squamous Cell Carcinoma by Array‐Based Comparative Genomic Hybridization
Author(s) -
Sparano Anthony,
Quesnelle Kelly M.,
Kumar Madhu S.,
Wang Yan,
Sylvester Albert J.,
Feldman Michael,
Sewell Duane A.,
Weinstein Gregory S.,
Brose Marcia S.
Publication year - 2006
Publication title -
the laryngoscope
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.181
H-Index - 148
eISSN - 1531-4995
pISSN - 0023-852X
DOI - 10.1097/01.mlg.0000205141.54471.7f
Subject(s) - comparative genomic hybridization , biology , mlh1 , carcinogenesis , gene , cancer , genetics , genome , cancer research , candidate gene , fanconi anemia , dna mismatch repair , dna repair
Objectives: 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.