Original article
Multiple reciprocal translocations in salivary gland mucoepidermoid carcinomas

https://doi.org/10.1016/j.cancergencyto.2003.10.007Get rights and content

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 reciprocal 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.

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, epithelial (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 intermediate cells. The origin of the intermediate cell type has not been conclusively established, although it is probably derived 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], [7], [8], [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 chromosomal abnormality in MEC; sometimes it is the only chromosomal rearrangement. This same translocation is also seen in Warthin tumor, a benign salivary gland tumor. We recently cloned the t(11;19) breakpoint and identified the fusion protein, MECT1-MAML2, resulting from this translocation [12], but little is known about other genomic and chromosomal aberrations present in MEC. For this reason, we used spectral karyotyping (SKY), CGH, and FISH to analyze two cell lines, H292 and H3118, derived from a lung and a parotid MEC, respectively.

Section snippets

Materials and methods

Tumor cell lines were generated at the U.S. National Naval Medical Center (Bethesda, MD) with institutionally approved tissue-procurement protocols, as previously described [12], [13], [14].

For preparation of the metaphase cells, we used standard cytogenetic procedures [15].

The spectral karyotyping hybridization protocol has been described in detail elsewhere [16], [17]. Slides were hybridized simultaneously with a spectral karyotyping probe mixture containing 24 distinctly labeled

Results

H292 was hyperdiploid (range 47–51) and H3118 was near-diploid (range 43–52) (Fig. 1). No variation in ploidy was evident in either cell line. H292 showed 12 clonal translocations (6 reciprocal), no deletions, and two isochromosomes; H3118 showed 11 translocations (8 reciprocal), 5 deletions, and 2 isochromosomes. No insertions were detectable in either cell line. In H292, a duplication at 1q31 was found. The only reciprocal translocation common to both cell lines was t(11;19)(q21;p13), which

Discussion

The presence of multiple reciprocal translocations (RTs) is the most striking finding of this study. This specific kind of chromosomal rearrangement is a common feature of hematological tumors and a subset of sarcomas. In some instances, RTs are present in multiple copies [11]. In contrast, karyotypes in epithelial cancers present numerous nonreciprocal rearrangements, but rarely show RTs [27]. Reciprocal translocations have been recently described in epithelial cancers, but these are usually

Acknowledgments

We wish to thank Dr. M.A. Pujana, Dr. X. Estivill, Dr. P.H.B. Sorensen, and Dr. B.D. Nelkin for providing specific probes for NTRK3. Dr. M. Kuehl, Dr. S. Lababidi, and Dr. A. Roschke are gratefully acknowledged for helpful discussion and Dr. S. Guerzoni for constant inspiration.

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