Cytogenetic and molecular observations in human and experimental salivary gland tumors

Sandros, Jens; Stenman, Göran; Mark, Joachim

doi:10.1016/0165-4608(90)90042-9

Cited by 128 publications

(107 citation statements)

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“…Extensive cytogenetic studies have revealed a highly speci®c pattern of chromosomal abnormalities (Sandros et al, 1990;Bullerdiek et al, 1993). In addition to a large group of adenomas with a normal stemline (about 30%), there are several subgroups characterized by mainly structural deviations and, in particular, reciprocal translocations.…”

Section: Introductionmentioning

confidence: 99%

The recurrent translocation t(5;8)(p13;q12) in pleomorphic adenomas results in upregulation of PLAG1 gene expression under control of the LIFR promoter

et al. 1998

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We have previously shown that the PLAG1 gene on chromosome 8q12 is consistently rearranged in pleomorphic adenomas of the salivary glands with t(3;8)(p21;q12) translocations. The t(3;8) results in promoter swapping between the PLAG1 gene, which encodes a novel zinc ®nger protein, and the constitutively expressed gene for b-catenin (CTNNB1), a protein with roles in cell-cell adhesion and the WG/WNT signalling pathway. In order to assess the importance of other translocation partner genes of PLAG1, and their possible relationship to CTNNB1, we have characterized a second recurrent translocation, i.e. the t(5;8)(p13;q12). This translocation leads to ectopic expression of a chimeric transcript consisting of sequences from the ubiquitously expressed gene for the leukemia inhibitory factor receptor (LIFR) and PLAG1. As for the t(3;8), the fusions occurred in the 5'-noncoding regions of both genes, exchanging regulatory control elements while preserving the coding sequences. The results of the current as well as previous studies indicate that ectopic expression of PLAG1 under the control of promoters of distinct translocation partner genes is a general pathogenetic mechanism for pleomorphic adenomas with 8q12 aberrations.

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Section: Introductionmentioning

confidence: 99%

The recurrent translocation t(5;8)(p13;q12) in pleomorphic adenomas results in upregulation of PLAG1 gene expression under control of the LIFR promoter

et al. 1998

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“…This is consistent with a previous survey of mammary tumor phenotypes in MMTV-Ras, MMTVMyc, and/or MMTV-Neu transgenic mice, where tumor morphology was closely correlated with the activated oncogene expressed (Cardiff et al, 1991). Accumulating cytogenetic and molecular biologic data indicate that specific human salivary tumors are often associated with predictable molecular perturbations (reviewed in Cerilli et al, 1999;El-Naggar et al, 1997;Johns et al, 1996;Sandros et al, 1990).…”

Section: Dardick Et Almentioning

confidence: 99%

Submandibular Gland Adenocarcinoma of Intercalated Duct Origin in Smgb-Tag Mice

Dardick

Paulus

et al. 2000

Laboratory Investigation

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SUMMARY:A line of transgenic mice that develops submandibular gland adenocarcinoma of intercalated duct origin was established. In these mice, the oncogene SV40 T antigen (Tag) is expressed from the neonatal submandibular gland secretory protein b (Smgb) gene promoter. This hybrid gene directs expression of the oncoprotein to neonatal submandibular gland proacinar and terminal tubule cells and to intercalated ducts of the adult gland. Transgene expression resulted in duct luminal cell hyperplasia as early as 20 to 30 days postnatally, which progressed to dysplasia by 3 to 4 months of age. Marked dysplasia and in situ carcinoma were evident at 4 to 6 months of age. All histologic changes were more pronounced in males. Submandibular gland adenocarcinoma developed stochastically in more than half of the adult male mice by 12 months of age (average age: 10.8 months, range: 6 to 13.5 months). Tag expression persisted in in situ carcinoma and all tumors. Using a combination of immunocytochemical and ultrastructural criteria, submandibular gland dysplasia and tumors were found to originate from intercalated ducts. The dysplastic ducts and adenocarcinoma in Smgb-Tag mice were morphologically similar to previously reported Tag-induced dysplasias of striated ducts and granular convoluted tubules and a Tag-induced adenocarcinoma of striated duct origin. These findings demonstrate that salivary gland dysplasias and tumors of similar histologic appearance can arise from distinct differentiated cell types. Analysis of the molecular changes accompanying tumor formation in Smgb-Tag mice could increase knowledge of human salivary gland tumorigenesis. (Lab Invest 2000, 80:1657-1670.

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“…1,2 Extensive cytogenetic studies have revealed that these tumors have highly specific chromosome abnormalities namely 3p21, 8q12 and 12q13-15 rearrangements and trisomy 8. [3][4][5][6] Among them, 8q12 deviations constitute the largest cytogenetic subgroup, the most frequent structural aberration being the reciprocal translocation t(3;8)(p21;q12). Molecular characterization of the t(3;8) translocation allowed the identification of two genes, PLAG1 and CTNNB1 involved at 8q12 and 3p21, respectively.…”

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PLAG1 gene alterations in salivary gland pleomorphic adenoma and carcinoma ex-pleomorphic adenoma: a combined study using chromosome banding, in situ hybridization and immunocytochemistry

et al. 2005

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Pleomorphic adenoma is the most common benign tumor of the salivary glands. It has marked histological diversity with epithelial, myoepithelial and mesenchymal-type cells arranged in a variety of architectural and differentiation patterns. Pleomorphic adenoma gene 1 (PLAG1), shown to be consistently rearranged in pleomorphic adenomas, is activated by chromosomal translocations involving 8q12, the chromosome region that is most frequently affected in these tumors. In this study, we evaluated PLAG1 involvement in salivary gland tumorigenesis by determining the frequency of its alterations in a selected group of 20 salivary gland tumors: 16 pleomorphic adenomas and four carcinomas ex-pleomorphic adenoma, having in common the presence of karyotypic chromosome 8 deviations, either structural, with 8q12 rearrangements, or numerical, with gain of chromosome 8. PLAG1 status was analyzed using in situ hybridization techniques, on metaphase cells, by fluorescence detection and/or interphase cells in paraffin sections, by chromogenic detection. Except for one pleomorphic adenoma case (5%) that lacked PLAG1 involvement, 17 tumors (85%), (14 pleomorphic adenomas and three carcinomas ex-pleomorphic adenoma) showed intragenic rearrangements of PLAG1 and the remaining two cases (10%), (one pleomorphic adenoma and one carcinoma ex-pleomorphic adenoma), had chromosome trisomy 8 only. To further investigate the role of PLAG1 on pleomorphic adenomas tumorigenesis, as well as the putative morphogenesis mechanism, we attempted to identify the cell types (epithelial vs myoepithelial) carrying 8q12/PLAG1 abnormalities by a combined phenotypic/genotypic analysis in four cases (three pleomorphic adenoma and one carcinoma ex-pleomorphic adenoma) characterized by 8q12 translocations and PLAG1 rearrangement. In these cases, both cells populations carried PLAG1 rearrangements. This finding further supports the pluripotent single-cell theory, which postulates that the tumor-initiated, modified myoepithelial cell, evolves into the varied somatic cell phenotypes present in pleomorphic adenoma, and reinforces the role of PLAG1 on the tumorigenesis of benign and malignant pleomorphic adenoma.

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Cytogenetic and molecular observations in human and experimental salivary gland tumors

Cited by 128 publications

References 38 publications

The recurrent translocation t(5;8)(p13;q12) in pleomorphic adenomas results in upregulation of PLAG1 gene expression under control of the LIFR promoter

The recurrent translocation t(5;8)(p13;q12) in pleomorphic adenomas results in upregulation of PLAG1 gene expression under control of the LIFR promoter

Submandibular Gland Adenocarcinoma of Intercalated Duct Origin in Smgb-Tag Mice

PLAG1 gene alterations in salivary gland pleomorphic adenoma and carcinoma ex-pleomorphic adenoma: a combined study using chromosome banding, in situ hybridization and immunocytochemistry

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