Detailed Genome-Wide SNP Analysis of Major Salivary Carcinomas Localizes Subtype-Specific Chromosome Sites and Oncogenes of Potential Clinical Significance

作者：Zhang Li; Mitani Yoshitsugu; Caulin Carlos; Rao Pulivarthi H; Kies Merrill S; Saintigny Pierre; Zhang Nianxiang; Weber Randal S; Lippman Scott M; El Naggar Adel K^*

来源：American Journal Of Pathology, 2013, 182(6): 2048-2057.

DOI：10.1016/j.ajpath.2013.02.020

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 SOC. 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 SOC. A comparative CNA analysis of fusion-positive and fusion-negative ACCs and MECs revealed relatively tower 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.

• 出版日期2013-6