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DNA Copy Number Gains at Loci of Growth Factors and Their Receptors in Salivary Gland Adenoid Cystic Carcinoma

Authors' Affiliations: ¹ Department of Oral and Maxillofacial Surgery/Oral Pathology, Academic Centre for Dentistry Amsterdam, ² Department of Pathology, ³ Department of Otolaryngology-Head and Neck Surgery, ⁴ Department of Biostatistics, and ⁵ Department of Mathematics, VU University Medical Center, Amsterdam, the Netherlands

Requests for reprints: Hedy Vékony, VU University Medical Center, Cancer Center Amsterdam, Room 2.21, P.O. Box 7057, 1007 MB Amsterdam, the Netherlands. Phone: 31-20-444-2317; E-mail: h.vekony{at}vumc.nl.

Purpose: Adenoid cystic carcinoma (ACC) is a malignant salivary gland tumor with a high mortality rate due to late, distant metastases. This study aimed at unraveling common genetic abnormalities associated with ACC. Additionally, chromosomal changes were correlated with patient characteristics and survival.

Experimental Design: Microarray-based comparative genomic hybridization was done to a series of 18 paraffin-embedded primary ACCs using a genome-wide scanning BAC array.

Results: A total of 238 aberrations were detected, representing more gains than losses (205 versus 33, respectively). Most frequent gains (>60%) were observed at 9q33.3-q34.3, 11q13.3, 11q23.3, 19p13.3-p13.11, 19q12-q13.43, 21q22.3, and 22q13.33. These loci harbor numerous growth factor [fibroblast growth factor (FGF) and platelet-derived growth factor (PDGF)] and growth factors receptor (FGFR3 and PDGFRß) genes. Gains at the FGF(R) regions occurred significantly more frequently in the recurred/metastasized ACCs compared with indolent ACCs. Furthermore, patients with 17 or more chromosomal aberrations had a significantly less favorable outcome than patients with fewer chromosomal aberrations (log-rank = 5.2; P = 0.02).

Conclusions: Frequent DNA copy number gains at loci of growth factors and their receptors suggest their involvement in ACC initiation and progression. Additionally, the presence of FGFR3 and PDGFRß in increased chromosomal regions suggests a possible role for autocrine stimulation in ACC tumorigenesis.

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