Use of single nucleotide polymorphism arrays to identify a novel region of loss on chromosome 6q in squamous cell carcinomas of the oral cavity.
BACKGROUND
A subset of patients with oral cavity squamous cell carcinoma(SCC), often of young age yet lacking a history of carcinogen exposure, has been identified, with no clear etiology for tumor development.


METHODS
To identify somatic genetic alterations unique to this patient population, we performed a high throughput single nucleotide polymorphism (SNP) analysis, quantitative PCR of the E6 and E7 regions of human papillomavirus (HPV) 16, sequencing of the IVSF-4+ locus of the FANC-C gene, and microsatellite analysis for 18 nonsmoking patients, age 23 to 57 years (median age, 39 years). We compared these results with oral SCC from 17 patients 47 to 81 (median, 64) years of age with significant tobacco exposure (>40 pack-years) to identify unique genetic alterations for each group.


RESULTS
SNP analysis demonstrated variable rates of allelic imbalance (AI) and no significant difference in terms of AI patterns between the two groups. However, we found an elevated rate of AI in chromosomal arms 6q (47% [17 of 36]) by performing microsatellite analysis of both groups. Only one tumor demonstrated the presence of HPV 16, and none of the tumors demonstrated mutations in the IVSF-4+ region of FANC-C.


CONCLUSIONS
Despite variable marker density, SNP array analysis is an emerging technique for genome-wide assessment and is a useful tool for discovery of novel sites of allelic loss in oral SCC, including a novel region of allelic loss on chromosome 6q.
Tong
Betty C
BC
Department of Otolaryngology-Head and Neck Surgery, Head and Neck Cancer Research Division, Johns Hopkins Medical School, 818 Ross Research Building, 720 Rutland Avenue, Baltimore, Maryland 21205-2196, USA.
Dhir
Karan
K
Ha
Patrick K
PK
Westra
William H
WH
Alter
Blanche P
BP
Sidransky
David
D
Koch
Wayne M
WM
Califano
Joseph A
JA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D022981:Allelic Imbalance; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D004273:DNA, Neoplasm / Q000032:analysis; D006801:Humans; D018895:Microsatellite Repeats; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D012907:Smoking / Q000235:genetics
D004273:DNA, Neoplasm