Deletion of 1p32-p36 Is the Most Frequent Genetic Change and Poor Prognostic Marker in Adenoid Cystic Carcinoma of the Salivary Glands

Texas Children's Cancer Center, Baylor College of Medicine, The University of Texas M. D. Anderson Cancer Center and Spectral Genomics, Houston, Texas, USA.
Clinical Cancer Research (Impact Factor: 8.72). 09/2008; 14(16):5181-7. DOI: 10.1158/1078-0432.CCR-08-0158
Source: PubMed


Adenoid cystic carcinoma (ACC) is a relatively uncommon salivary gland malignancy known for its protean phenotypic features and pernicious clinical behavior. Currently, no effective therapy is available for patients with advanced nonresectable, recurrent, and/or metastatic disease. The purpose of this study is to identify prognostic factors other than tumor stage that can be used to predict the outcome of the patients with ACC.
We used comparative genomic hybridization (CGH) to identify copy number aberrations in 53 primary ACCs. Array CGH and fluorescence in situ hybridization analysis was used to validate CGH results on selected cases. We correlated these copy number aberrations with clinicopathologic factors using Pearson's chi2 or by the two-tailed Fisher exact test. The disease-specific survival and disease-free intervals were generated by the Kaplan-Meier product limit method.
Chromosomal losses (n = 134) were more frequent than gains (n = 74). The most frequent genetic change was the loss of 1p32-p36 in 44% of the cases followed by 6q23-q27, and 12q12-q14. The most frequently gained chromosomal regions were 8 and 18. Of the chromosomal aberrations, loss of 1p32-p36 was the only abnormality significantly associated with patient's outcome.
This study, for the first time, identifies loss of 1p32-p36 as a significant aberration in ACC. Molecular characterization of 1p32-36 region using the available genomic technologies may lead to the identification of new genes critical to the development of novel therapeutic targets for this disease copy number aberration.

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    • "Epigenetic changes, which are defined as modifications of the chromatin structure without alteration of the primary DNA sequence (Jaenisch & Bird, 2003), may be induced by external factors and are potentially reversible. LOH at human chromosome 1p32 is frequent in various cancers, including lung cancer (Chizhikov et al, 2001; Fong et al, 1996), breast cancer (el-Rifai et al, 1999), meningioma (Kim et al, 2009; Sulman et al, 1998), adenoid cystic carcinoma (Rao et al, 2008) and oligodendroglia (Husemann et al, 1999). Thus, this region of chromosome 1 is expected to contain one or more tumour suppressor genes. "
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