Cancer Genetics and Cytogenetics 152 (2004) 15–22 Multiple reciprocal translocations in salivary gland mucoepidermoid carcinomas Giovanni Tonon, Kristen Stover Gehlhaus, Raluca Yonescu, Frederic J. Kaye, Ilan R. Kirsch* Genetics Branch, National Cancer Institute, NNMC, 8901 Wisconsin Avenue, Bldg. 8, Room 5101, Bethesda, MD 20889-5105 Received 1 August 2003; received in revised form 6 October 2003; accepted 10 October 2003 Abstract Mucoepidermoid carcinoma, the most common human malignant salivary gland tumor, can arise from both major and minor salivary glands, including sites within the pulmonary tracheobronchial tree. We performed comparative genomic hybridization (CGH) and spectral karyotyping (SKY) on two tumor cell lines: H3118, derived from tumor originating in the parotid gland, and H292, from tumor in the lung. In both cell lines, CGH showed a partial gain within the short arm of chromosome 7 and SKY revealed the presence of the previously reported reciprocal translocation t(11;19)(q21;p12). Additional chromosomal rearrangements were found in both cell lines, including three more reciprocal translocations in cell line H292 [t(1;16), t(6;8)×2] and three other recipro- cal translocations in cell line H3118 [t(1;7), t(3;15), and t(7;15)]. A review of the literature of other reported cases of mucoepidermoid carcinomas analyzed with standard G-banding techniques, as well as distinct benign salivary gland tumors, such as pleomorphic adenomas and Warthin tumor, confirmed the presence of a karyotype dominated by reciprocal translocations. Four chromosomal bands were involved in chromosomal translocations in both cell lines: 1q32, 5p15, 7q22, and 15q22. Fluorescence in situ hybridization studies showed that the breakpoints in these four bands were often within a few megabases of each other. The involvement of similar chromosomal bands in breakpoints in these two cell lines suggests that these regions may be predisposed or selected for chromosomal rearrangements in this tumor type. The presence of multiple reciprocal translocations in both benign and malignant salivary gland tumors may also suggest a particular mechanism within mucous or serous glands mediating chromosomal rearrangements.  2004 Elsevier Inc. All rights reserved. 1. Introduction Mucoepidermoid carcinoma (MEC) is the most frequent malignant tumor of the salivary glands. In approximately half of the cases, it involves one of the major salivary glands, principally the parotid; when affecting the minor glands, it usually originates in the oval palate, less often in the larynx, trachea, or bronchoalveolar tract. MEC consists of three cellular populations: mucous, epi- thelial (squamous), and intermediate cells; the latter are the only replicating cell type and thus may be responsible for tumor formation [1]. The mucous and epithelial cells do not appear to proliferate and may be derived from the intermedi- ate cells. The origin of the intermediate cell type has not * Corresponding author. Tel.: (301) 402-6382; fax: (301) 496-0047. E-mail address: kirschi@exchange.nih.gov (I.R. Kirsch). 0165-4608/04/$ – see front matter  2004 Elsevier Inc. All rights reserved. doi:10.1016/j.cancergencyto.2003.10.007 been conclusively established, although it is probably de- rived from the striated duct [2,3]. MECs are subdivided histologically into low and high grade. The low-grade tumors are usually curable, whereas patients with high-grade tumors often experience recurrence of the disease and have a poor prognosis [4,5]. Radiation exposure is among the major risk factors for this tumor. This association was first noticed in atomic bomb survivors and then confirmed by several other studies [6–9]. A comprehensive cytogenetic analysis of MEC is not available. Moreover, except for one reported case in which multicolor combined binary ratio labeling fluorescence in situ hybridization (COBRA-FISH) was performed [10], all the previously described MEC karyotypes are based on G- banding analysis [11]. To our knowledge, no comparative genomic hybridization (CGH) analyses for this tumor have been published. The reciprocal t(11;19)(q21;p13) is the major chromo- somal abnormality in MEC; sometimes it is the only