DNA copy number gains at loci of growth factors and their receptors in salivary gland adenoid cystic carcinoma.
OBJECTIVE
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.


METHODS
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 PDGFRbeta) 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 PDGFRbeta in increased chromosomal regions suggests a possible role for autocrine stimulation in ACC tumorigenesis.
Vékony
Hedy
H
Department of Oral and Maxillofacial Surgery/Oral Pathology, Academic Centre for Dentistry Amsterdam, the Netherlands. h.vekony@vumc.nl
Ylstra
Bauke
B
Wilting
Saskia M
SM
Meijer
Gerrit A
GA
van de Wiel
Mark A
MA
Leemans
C René
CR
van der Waal
Isaäc
I
Bloemena
Elisabeth
E
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003528:Carcinoma, Adenoid Cystic / Q000235:genetics / Q000473:pathology*; D004273:DNA, Neoplasm / Q000378:metabolism*; D005260:Female; D005346:Fibroblast Growth Factors / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000378:metabolism; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D012468:Salivary Gland Neoplasms / Q000235:genetics / Q000473:pathology*
D004273:DNA, Neoplasm; D036341:Intercellular Signaling Peptides and Proteins; D010982:Platelet-Derived Growth Factor; D005346:Fibroblast Growth Factors; C496365:FGFR3 protein, human; D051498:Receptor, Fibroblast Growth Factor, Type 3; D020797:Receptor, Platelet-Derived Growth Factor beta