PURPOSE: 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. EXPERIMENTAL DESIGN: 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. RESULTS: 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. CONCLUSIONS: 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.
PURPOSE: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. EXPERIMENTAL DESIGN: 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. RESULTS: 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. CONCLUSIONS: 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.
Authors: Li Zhang; Yoshitsugu Mitani; Carlos Caulin; Pulivarthi H Rao; Merrill S Kies; Pierre Saintigny; Nianxiang Zhang; Randal S Weber; Scott M Lippman; Adel K El-Naggar Journal: Am J Pathol Date: 2013-04-10 Impact factor: 4.307
Authors: Philip J Stephens; Helen R Davies; Yoshitsugu Mitani; Peter Van Loo; Adam Shlien; Patrick S Tarpey; Elli Papaemmanuil; Angela Cheverton; Graham R Bignell; Adam P Butler; John Gamble; Stephen Gamble; Claire Hardy; Jonathan Hinton; Mingming Jia; Alagu Jayakumar; David Jones; Calli Latimer; Stuart McLaren; David J McBride; Andrew Menzies; Laura Mudie; Mark Maddison; Keiran Raine; Serena Nik-Zainal; Sarah O'Meara; Jon W Teague; Ignacio Varela; David C Wedge; Ian Whitmore; Scott M Lippman; Ultan McDermott; Michael R Stratton; Peter J Campbell; Adel K El-Naggar; P Andrew Futreal Journal: J Clin Invest Date: 2013-06-17 Impact factor: 14.808