Deletion of1p32-p36 Is the Most Frequent Genetic Change and
Poor Prognostic Marker in Adenoid Cystic Carcinoma of
the Salivary Glands
Pulivarthi H. Rao,1Diana Roberts,3Yi-Jue Zhao,1Diana Bell,3Charles P. Harris,4
Randal S.Weber,2and Adel K. El-Naggar3
Purpose: Adenoid cystic carcinoma (ACC) is a relatively uncommon salivary gland malignancy
knownforitsproteanphenotypic features andpernicious clinicalbehavior. Currently, no effective
therapy is available for patients with advanced nonresectable, recurrent, and/or metastatic dis-
ease.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
with clinicopathologic factors using Pearson’s m2or by the two-tailed Fisher exact test. The
disease-specific survival and disease-free intervals were generated by the Kaplan-Meier product
Results: Chromosomal losses (n = 134) were more frequent than gains (n = 74). The most
frequent genetic change was the loss of1p32-p36 in 44% of the cases followed by 6q23-q27,
and12q12-q14.The most frequently gained chromosomal regions were 8 and18. Of thechromo-
somal aberrations, loss of 1p32-p36 was the only abnormality significantly associated with
Conclusions:This study, for the first time, identifies loss of1p32-p36 as a significant aberration
in ACC. Molecular characterization of 1p32-36 region using the available genomic technologies
for this disease copy numberaberration.
Adenoid cystic carcinoma (ACC) is an uncommon salivary
gland malignancy characterized by heterogeneous phenotypic
features and persistently progressive biological behavior
(1–6). Histopathologically, ACC manifests three histologic
patterns, including the solid, cribriform, and tubular forms, in
variable combination and dominance (7). The solid pattern is
typically associated with aggressive clinical course. ACCs are
known for their proclivity to perineural invasion, which
significantly contribute to the intractable nature of this disease
(1, 8, 9). Surgical resection with and without postoperative
radiotherapy remains the primary treatment modality for the
management of this disease. However, patients with advanced
local presentation, recurrence, and/or distant metastasis have
limited therapeutic options (8, 9). Therefore, elucidation of
molecular events that predict the malignant risk is critical in
understanding the biology, clinical behavior, and manage-
ment of ACC.
Previous conventional cytogenetic studies of ACC, although
limited in numbers and scope, have revealed translocations
involving chromosome 6q with multiple chromosomal part-
ners (10, 11). Subsequent analysis, using comparative genomic
hybridization (CGH) of these tumors have reported recurrent
chromosomal gains of 16p, 17q, 19, and 22q13 and losses at
6q23-qter, 12q12-q13, 13q21-q22, and 19 (12, 13). Recently,
an array CGH study of 18 paraffin-embedded primary ACCs
have reported frequent gains at 9q33.3-q34.3, 11q13.3,
11q23.3, 19q13.3-p13.11, 19q12-q13.43, 21q22.3, and
22q13.33 (14). Several molecular genetic studies also have
been attempted to define the genetic alterations and identified
frequent loss of heterozygosity at 6q, 12q12-q13, and 17p
chromosomal regions, suggesting the presence of putative
tumor suppressor genes on these chromosomes (15–19). Gene
expression studies of ACC have identified a gene signature that
is associated with early development, cell cycle regulation,
apoptosis, myoepithelial differentiation, and extracellular
matrix (20, 21). In addition, overexpression of transcriptional
Imaging, Diagnosis, Prognosis
Departments of2Pathology,3Head and Neck Surgery,The University ofTexas M. D.
Anderson Cancer Centerand4Spectral Genomics, Houston,Texas
Received1/20/08; revised 4/12/08; accepted 4/16/08.
Grant support: National Cancer Institute Specialized Program of Research
Excellence in head and neck cancer grant (P.H. Rao and A.E. Naggar) and in part
by the Kenneth D. Mu « ller Professorship and the National Cancer Institute grant
CA-16672 (A.E. Naggar).
The costs of publicationof this articlewere defrayedinpart by the paymentof page
charges.This article must therefore be hereby marked advertisement in accordance
with18 U.S.C. Section1734 solely toindicatethis fact.
Requests for reprints: Pulivarthi H. Rao,Texas Children’s Cancer Center, Baylor
College of Medicine, 6621Fannin Street, MC 3-3320, Houston,TX 77030. Phone:
832-824-4820; Fax: 832-825-4038; E-mail: firstname.lastname@example.org.
F2008 American Association for Cancer Research.
www.aacrjournals.org Clin Cancer Res 2008;14(16) August15, 20085181
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