Genomic profiling of adenoid cystic carcinomas

Objectives: Salivary gland tumours are rare neoplasms that show various morphological patterns as well as a diverse clinical behaviour. Their classification depends solely on histopathological features. The precise genetic alterations that underlie these neoplasms have been poorly characterized. A better understanding of these aberrations in salivary gland tumour development and progression could significantly improve classification and prognostication of these tumours. One high-resolution technique that detects and maps changes in copy number of DNA sequences is microarray based comparative genomic hybridization (arrayCGH). It provides a global overview of chromosomal gains and losses throughout the whole genome of a tumour and allows subsequent associations to be made with clinical outcome.

Methods: Archival formalin-fixed paraffin-embedded tissue samples from 18 primary adenoid cystic carcinomas (ACCs) were used. ACC were localized in the major salivary glands (parotid n=8, submandibular n=8, sublingual n=1) or elsewhere in the oral cavity (n=1). The male-female ratio was 1:2, the mean age at diagnosis was 51 (range 25-81) and the mean follow-up time was 72 (range 7-128) months. Eight patients (45%) developed either a recurrence or a metastasis. Six patients (33%) died of disease. DNA was isolated and the chromosomal aberrations in these tumours were analysed by arrayCGH using a 5K BAC array platform. To detect chromosomal regions that statistically significantly differ between patients with and without metastases, the Wilcoxon two-sample statistic with ties was used.

Results: In all ACCs, chromosomal aberrations were observed, with gains being far more frequent than losses. A 5 Mbp gain at chromosome 5q31.3-32 was related to the occurrence of metastases.

Conclusions: Adenoid cystic carcinomas show frequent chromosomal aberrations with arrayCGH. A discrete region at 5q31.3-32 seems to be correlated to the development of metastases. Currently, the genes of interest in this region are further mapped.