title: Detailed genome-wide SNP analysis of major salivary carcinomas localizes subtype-specific chromosome sites and oncogenes of potential clinical significance.
abstract: The molecular genetic alterations underlying the development and diversity of salivary gland carcinomas are largely unknown. To characterize these events, comparative genomic hybridization analysis was performed, using a single-nucleotide polymorphism microarray platform, of 60 fresh-frozen specimens that represent the main salivary carcinoma types: mucoepidermoid carcinoma (MEC), adenoid cystic carcinoma (ACC), and salivary duct carcinoma (SDC). The results were correlated with the clinicopathologic features and translocation statuses to characterize the genetic alterations. The most commonly shared copy number abnormalities (CNAs) in all types were losses at chromosomes 6q23-26 and the 9p21 region. Subtype-specific CNAs included a loss at 12q11-12 in ACC and a gain at 17q11-12 in SDC. Focal copy number losses included 1p36.33-p36-22 in ACC, 9p13.2 in MEC, and 3p12.3-q11-2, 6q21-22.1, 12q14.1, and 12q15 in SDC. Tumor-specific amplicons were identified at 11q23.3 (PVRL1) in ACC, 11q13.3 (NUMA1) in MEC, and 6p21.1 (CCND3), 9p13.2 (PAX5), 12q15 (CNOT2/RAB3IP), 12q21.1 (GLIPR1L1), and 17q12 (ERBB2/CCL4) in SDC. A comparative CNA analysis of fusion-positive and fusion-negative ACCs and MECs revealed relatively lower CNAs in fusion-positive tumors than in fusion-negative tumors in both tumor types. An association between CNAs and high grade and advanced stage was observed in MECs only. These findings support the pathogenetic segregation of these entities and define novel chromosomal sites for future identification of biomarkers and therapeutic targets.
authors.affiliation: Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA. lzhangli@mdanderson.org
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Yoshitsugu
authors.initials: Y
authors.lastname: Mitani
authors.forename: Carlos
authors.initials: C
authors.lastname: Caulin
authors.forename: Pulivarthi H
authors.initials: PH
authors.lastname: Rao
authors.forename: Merrill S
authors.initials: MS
authors.lastname: Kies
authors.forename: Pierre
authors.initials: P
authors.lastname: Saintigny
authors.forename: Nianxiang
authors.initials: N
authors.lastname: Zhang
authors.forename: Randal S
authors.initials: RS
authors.lastname: Weber
authors.forename: Scott M
authors.initials: SM
authors.lastname: Lippman
authors.forename: Adel K
authors.initials: AK
authors.lastname: El-Naggar
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003528:Carcinoma, Adenoid Cystic / Q000235:genetics / Q000473:pathology; D044584:Carcinoma, Ductal / Q000235:genetics / Q000473:pathology; D018277:Carcinoma, Mucoepidermoid / Q000235:genetics / Q000473:pathology; D002874:Chromosome Mapping / Q000379:methods; D055028:Comparative Genomic Hybridization / Q000379:methods; D056915:DNA Copy Number Variations; D005260:Female; D055106:Genome-Wide Association Study / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009857:Oncogenes; D020641:Polymorphism, Single Nucleotide; D012468:Salivary Gland Neoplasms / Q000235:genetics* / Q000473:pathology; D055815:Young Adult