Concurrent loss of heterozygosity and copy number analysis in adenoid cystic carcinoma by SNP genotyping arrays.
Adenoid cystic carcinoma (ACC) is one of the most common malignancies to arise in the salivary glands, yet very little is known of the genetic alterations that are involved in the pathogenesis of this disease. To further examine the genetic changes that underlie ACC, we analyzed genomic DNA obtained from 22 primary ACC and two ACC-derived cell lines by high-density oligonucleotide single-nucleotide polymorphism genotyping arrays (Affymetrix GeneChip Human Mapping 100K Set). Allelotype calls were analyzed by the Haplotype Correction version of the Linkage Disequilibrium Hidden Markov Model to determine loss of heterozygosity using information derived only from tumor samples. Comparison of data obtained from matched tumor-normal samples suggested that only deletion calls of >3 Mb were reliable. Within these parameters, ACC samples revealed a mean of three deletions per tumor, and no consensus areas of deletion were observed across the majority of tumors. Similarly, copy number analysis of primary hybridization data revealed no consensus areas of gene amplification. This is in contrast to a much higher rate of genomic alterations detected in a cohort of squamous carcinomas analyzed by the same methods. Our data show that most ACC have predominantly stable genomes, which is consistent with the theory that telomere crisis does not play a significant role in early stages of ACC tumor progression. Our data suggest that gene mutation and/or epigenetic events that cannot be detected by assay of gross alteration of chromosomal structure are likely to underlie the malignant transformation events of this tumor type.
Yu
Yongtao
Y
Department of Pathology, University of Virginia, Charlottesville, VA 22908, USA.
Baras
Alexander S
AS
Shirasuna
Kanemitsu
K
Frierson
Henry F
HF
Moskaluk
Christopher A
CA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003528:Carcinoma, Adenoid Cystic / Q000235:genetics* / Q000556:secondary; D045744:Cell Line, Tumor; D002872:Chromosome Deletion; D004252:DNA Mutational Analysis / Q000379:methods*; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D018628:Gene Dosage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012468:Salivary Gland Neoplasms / Q000235:genetics* / Q000473:pathology
D004273:DNA, Neoplasm