Original articleMultiple reciprocal translocations in salivary gland mucoepidermoid carcinomas
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.
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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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