Deletion of 1p32-p36 is the most frequent genetic change and poor prognostic marker in adenoid cystic carcinoma of the salivary glands.
OBJECTIVE
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.


METHODS
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.
Rao
Pulivarthi H
PH
Texas Children's Cancer Center, Baylor College of Medicine, The University of Texas M. D. Anderson Cancer Center and Spectral Genomics, Houston, Texas, USA. prao@bcm.tmc.edu
Roberts
Diana
D
Zhao
Yi-Jue
YJ
Bell
Diana
D
Harris
Charles P
CP
Weber
Randal S
RS
El-Naggar
Adel K
AK
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics*; D003528:Carcinoma, Adenoid Cystic / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012468:Salivary Gland Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D017384:Sequence Deletion / Q000235:genetics*
D014408:Biomarkers, Tumor