[en] Pleomorphic adenomas are benign epithelial tumors originating from the major and minor salivary glands. Extensive cytogenetic studies have demonstrated that they frequently show chromosome abnormalities involving chromosome 8, with consistent breakpoints at 8q12. In previous studies, we have shown that these breakpoints are located in a 9-cM interval between MOS/D8S285 and D8S260. Here, we describe directional chromosome walking studies starting from D8S260 as well as D8S285. Using the CEPH and ICRF YAC libraries, these studies resulted in the construction of two nonoverlapping YAC contigs of about 2 and 5 Mb, respectively. Initial fluorescence in situ hybridization (FISH) analysis suggested that the majority of 8q12 breakpoints clustered within the 2-Mb contig, which was mapped to the centromeric part of chromosome band 8q12. This contig has at least double coverage and consists of 34 overlapping YAC clones. The localization of the YACs was confirmed by FISH analysis. On the basis of mapping data of landmarks with an average spacing of 65 kb as well as restriction enzyme analysis, a long-range physical map was established for the chromosome region spanned by the 2-Mb contig. The relative positions of various known genes and expressed sequence tags within this contig were also determined. Subsequent FISH analyses of pleomorphic adenomas using YACs as well as cosmids revealed that all but two of the 8q12 breakpoints in the primary tumors tested mapped within a 300-kb interval between the MOS proto-oncogene and STS EM156. The target gene affected by the chromosome aberrations mapping within this interval was recently shown to be the PLAG1 gene, which encodes a novel zinc finger protein.
Disciplines :
Oncology
Author, co-author :
Kas, Koen; Center for Human Genetics, University of Leuven, and Flanders Interuniversity Institute for Biotechnology, Belgium
Röijer, Eva; Laboratory of Cancer Genetics, Department of Pathology, Göteborg University, S-413 45 Göteborg, Sweden
Voz, Marianne ; Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire ; Laboratory for Molecular Oncology, Center for Human Genetics, University of Leuven, B-3000 Leuven, Belgium
Meyen, Eva; Laboratory for Molecular Oncology, Center for Human Genetics, University of Leuven, B-3000 Leuven, Belgium
Stenman, Göran; Laboratory of Cancer Genetics, Department of Pathology, Göteborg University, S-413 45 Göteborg, Sweden
Van de Ven, Wim J. M.; Laboratory for Molecular Oncology, Center for Human Genetics, University of Leuven, B-3000 Leuven, Belgium
Language :
English
Title :
A 2-Mb YAC contig and physical map covering the chromosome 8q12 breakpoint cluster region in pleomorphic adenomas of the salivary glands.
The authors thank C. Huysmans, J. Geurts, and M. M. Behrendt for their contributions. We thank Nils Mandahl for providing tumor material from a lipoblastoma. This work was supported in part by the EU through the Biomed 1 program Molecular Cytogenetics of Solid Tumours, the Geconcerteerde Onderzoekacties 1997-2001, the Fonds voor Wetenschappelijk Onderzoek Vlaanderen (FWO), the ASLK-programma voor Kankeronderzoek, the Swedish Cancer Society, and the IngaBritt and Arne Lundbergs Research Foundation. K. Kas is a postdoc of the FWO. M. Voz has a stipend from the FWO program Kom op tegen Kanker.
Adam-Klages, S., Adam, D., Wiegmann, K., Struve, S., Kolanus, W., Schneider-Mergener, J., and Kronke, M. (1996). FAN, a novel WD-repeat protein, couples the p55 TNF-receptor to neutral sphingo-myelinase. Cell 86: 937-947.
Albertsen, H. M., Abderrahim, H., Cann, H. M., Dausset, J., Le Paslier, D., and Cohen, D. (1990). Construction and characterization of a yeast artificial chromosome library containing seven haploid human genome equivalents. Proc. Natl. Acad. Sci. USA 87: 4256-4260.
Altschul, S. F., Gish, W., Miller, W., Myers, E. W., and Lipman, D. J. (1990). Basic local alignment search tool. J. Mol. Biol. 215: 403-410.
Blunt, T., Finnie, N. J., Taccioli, G. E., Smith, G. C. MG. C., Demengeot, J., Gottlieb, T. M., Mizuta, R., Varghese, A. J., Alt, F. W., Jeggo, P. A., and Jackson, S. P. (1995). Defective DNA-dependent protein kinase activity is linked to V(D)J recombination and DNA repair defects associated with the murine scid mutation. Cell 80: 813-823.
Bullerdiek, J., Wobst, G., Meyer-Bolte, K., Chilla, R., Haubrich, J., Thode, B., and Bartnitzke, S. (1993). Cytogenetic subtyping of 220 salivary gland pleomorphic adenomas: Correlation to occurrence, histological subtype, and in vitro cellular behavior. Cancer Genet. Cytogenet. 65: 27-31.
Brunton, L. L., and Lupton, S. D. (1990). An STS in the human IL7 gene located at 8q12-13. Nucleic Acids Res. 18: 1315.
Chu, G., Vollrath, D., and Davis, R. W. (1986). Separation of large DNA molecules by contour-clamped homogeneous electric fields. Science 234: 1582-1585.
Chumakov, I., Rigault, P., Guillou, S., Ougen, P., Billaut, A., Guasconi, G., Gervy, P., LeGall, I., Soularue, P., Grinas, L., Bougueleret, L., Bellanné-Chantelot, C., Lacroix, B., Barillot, E., Gesnouin, P., Pook, S., Vaysseix, G., Frelat, G., Schmitz, A., Sambucy, J. L., Bosch, A., Estivill, X., Weissenbach, J., Vignal, A., Riethman, H., Cox, D., Patterson, D., Gardiner, K., Hattori, M., Sakaki, Y., Ichikawa, H., Ohki, M., Le Paslier, D., Heilig, R., Antonarakis, S., and Cohen, D. (1992). Continuum of overlapping clones spanning the entire human chromosome 21q. Nature 359: 380-387.
Cohen, D., Chumakov, I., and Weissenbach, J. (1993). A first-generation physical map of the human genome. Nature 366: 698-701.
Cohen, J. C. C., Cali, J. J., Jelinek, D. F., Mehrabian, M., Sparkes, R. S., Lusis, A. J., Russell, D. W., and Hobbs, H. H. (1992). Cloning of the human cholesterol 7α-hydroxylase gene (CYP7) and localization to chromosome 8q11-q12. Genomics 14: 153-161.
Corey, S. J., and Shapiro, D. N. (1994). Localization of the human gene for Src-related protein tyrosine kinase LYN to chromosome 8q11-12: A lymphoid signaling cluster? Leukemia 8: 1914-1917.
Craig, J. M., and Bickmore, W. A. (1993). Chromosome bands - Flavours to savour. BioEssays 15: 349-354.
Dal Cin, P., Sciot, R., De Wever, I., Van Damme, B., and Van Den Berghe, H. (1994). New discrimative chromosomal marker in adipose tissue tumors. The chromosome 8q11-q13 region in lipoblastoma. Cancer Genet. Cytogenet. 78: 232-235.
Dib, C., Faure, S., Fizames, C., Samson, D., Drouot, N., Vignal, A., Millasseau, P., Marc, S., Kazan, J., Seboun, E., Lathrop, M., Gyapay, G., Morissette, J., and Weissenbach, J. (1996). A comprehensive genetic map of the human genome based on 5264 microsatellites. Nature 380: 152-154.
Doerflinger, N., Linder, C., Ouahchi, K., Gyapay, G., Weissenbach, J., Le Paslier, D., Rigault, P., Belal, S., Ben Hamida, C., Hentati, F., Ben Hamida, M., Pandolfo, M., DiDonato, S., Sokol, R., Kayden, H., Landrieu, P., Durr, A., Brice, A., Goutieres, F., Kohlschutter, A., Sabouraud, P., Benomar, A., Yahyaoui, M., Mandel, J.-L., and Koenig, M. (1995). Ataxia with Vitamin E deficiency: Refinement of genetic localization and analysis of linkage disequilibrium by using new markers in 14 families. Am. J. Hum. Genet. 56: 1116-1124.
Elfving, P. (1996). Cytogenetic studies of normal kidney tissue and renal cell carcinoma. Thesis, Lund University, Lund.
Eyre, H., Akkari, P. A., Wilton, S. D., Gallen, D. C., Baker, E., and Laing, N. G. (1995). Assignment of the human skeletal muscle atropomyosin gene (TPM1) to band 15q22 by fluorescence in situ hybridization. Cytogenet. Cell Genet. 69: 15-17.
Feinberg, A. P., and Vogelstein, B. (1984). A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal. Biochem. 132: 6-13.
Geurts, J., Schoenmakers, H. F. P. M., Mols, R., and Van de Ven, W. J. M. (1994). Improved procedure for rapid isolation and sequencing of DNA insert termini in yeast artificial chromosomes. Methods Mol. Cell. Biol. 4: 257-265.
Green, E. D., and Olson, M. V. (1990). Systematic screening of yeast artificial-chromosome libraries by use of the polymerase chain reaction. Proc. Natl. Acad. Sci. USA 87: 1213-1217.
Gyapay, G., Morissette, J., Vignal, A., Dib, C., Fizames, C., Millasseau, P., Marc, S., Bernardi, G., Lathrop, M., and Weissenbach, J. (1994). The 1993-94 Généthon human genetic linkage map. Nature Genet. 7: 246-339.
Hrynchak, M., White, V., Berean, K., and Horsman, D. (1994). Cyto-genetic findings in seven lacrimal gland neoplasms. Cancer Genet. Cytogenet. 75: 133-138.
Kas, K., Voz, M., Röijer, E., Aström, A.-K., Meyen, E., Stenman, G., and Van de Ven, W. J. M. (1997). Promotor swapping between the genes for a novel zinc finger protein and β-catenin in pleomorphic adenomas with t(3;8)(p21;q12) translocations. Nature Genet. 15: 170-174.
Mitelman, F. (1994). "Catalog of Chromosome Aberrations in Cancer," 5th ed., Wiley-Liss, New York.
Mock, B. A., Stoye, J., Spence, J., Jackson, I., Eppig, J. T., Fiedorek, F. T., Jr., and Neumann, P. E. (1996). Encyclopedia of the mouse genome V, Mouse chromosome 4. Mamm. Genome 6: S73-S96.
Nelson, D. L., Ledbetter, S. A., Corbo, L., Victoria, M. F., Ramirez-Solis, R., Webster, T. D., Ledbetter, D. H., and Caskey, C. T. (1989). Alu polymerase chain reaction: A method for rapid isolation of human-specific sequences from complex DNA sources. Proc. Natl. Acad. Sci. USA 86: 6686-6690.
Röijer, E., Kas, K., Klawitz, I., Bullerdiek, J., Van de Ven, W., and Stenman, G. (1996). Identification of a Yeast Artificial Chromosome spanning the 8q12 translocation breakpoint in pleomorphic adenomas with t(3;8)(p21;q12). Genes Chromosomes Cancer 17: 166-171.
Röijer, E., Kas, K., Van de Ven, W., and Stenman, G. (1997). Mapping of the 8q12 translocation breakpoint to a 40-kb region in a pleomorphic adenoma with an ins(8;3)(q12;p21.3p14.1). Cytogenet. Cell. Genet. 76: 23-26.
Rychlik, W., and Rhoads, R. E. (1989). A computer program for choosing optimal oligonucleotides for filter hybridization, sequencing and in vitro amplification of DNA. Nucleic Acids Res. 17: 8543-8551.
Sambrook, J., Fritsch, E. F., and Maniatis, T. (1989). "Molecular Cloning: A Laboratory Manual," Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.
Sandros, J., Stenman, G., and Mark, J. (1990). Cytogenetic and molecular observations in human and experimental salivary gland tumors. Cancer Genet. Cytogenet. 44: 153-167.
Sapru, M., Gu, J., Gu, X., Smith, D., Yu, C.-E., Wells, D., and Wagner, M. (1994). A panel of radiation hybrids for chromosome 8. Genomics 21: 208-216.
Sawyer, J. R., Parsons, E. A., Crowson, M. L., Smith, S., Erickson, S., and Bell, J. M. (1994). Potential diagnostic implications of breakpoints in the long arm of chromosome 8 in lipoblastoma. Cancer Genet. Cytogenet. 76: 39-42.
Schoenmakers, E. F. P. M., Kools, P. F. J., Mois, R., Kazmierczak, B., Bartnitzke, S., Bullerdiek, J., Dal Cin, P., De Jong, P. J., Van den Berghe, H., and Van de Ven, W. J. M. (1994). Physical mapping of chromosome 12q breakpoints in lipoma, pleomorphic salivary gland adenoma, uterine leiomyoma, and myxoid liposarcoma. Genomics 20: 210-222.
Schoenmakers, E. F. P. M., Wanschura, S., Mols, R., Bullerdiek, J., Van den Berghe, H., and Van de Ven, W. J. M. (1995). Recurrent rearrangements in the high mobility group protein gene, HMGI-C, in benign mesenchymal tumours. Nature Genet. 10: 436-444.
Seifert, G., Miehlke, A., Haubrich, J., and Chilla, R. (1986). Diseases of the salivary glands. In "Pathology Diagnosis. Treatment. Facial Nerve Surgery," pp. 182-194, Thieme, Stuttgart/New York. [Translated by P. M. Stell]
Tachibana, K., Umezawa, A., Kato, S., and Takano, T. (1988). Nucleotide sequence of a new YPT1-related human cDNA which belongs to the ras gene superfamily. Nucleic Acids Res. 16: 10368.
Testa, J. R., Parsa, N. Z., Le Beau, M. M., and Vande Woude, G. F. (1988). Localization of the proto-oncogene MOS to 8q11-q12 by in situ chromosomal hybridization. Genomics 3: 44-47.
Tomfohrde, J., Wood, S., Schertzer, M., Wagner, M. J., Wells, D. E., Parrish, J., Sadler, L. A., Blanton, S. H., Daiger, S. P., Wang, Z., Wilkie, P. J., and Weber, J. L. (1992). Human chromosome 8 linkage map based on short tandem repeat polymorphisms: Effect of genotyping errors. Genomics 14: 144-152.
Van Ommen, G. J. (1993). First report of the HUGO YAC committee. In "Genome Priority Reports" (A. J. Cuticchia, P. L. Parson, and H. P. Klinger, Eds.), Vol. 1, pp. 885-888, Karger, Basel.
Waldron, C. A. (1991). Mixed tumor (Pleomorphic adenoma) and myoepithelioma. In "Surgical Pathology of the Salivary Glands" (G. L. Ellis, P. L. Auclair, and D. R. Gnepp, Eds.), pp. 165-186, Saunders, Philadelphia.
Wood, S., Schertzer, M., Drabkin, H., Patterson, D., Longmire, J. L., and Deaven, L. L. (1992). Characterization of a human chromosome 8 cosmid library constructed from flow-sorted chromosomes. Cytogenet. Cell Genet. 59: 243-247.
Yasuda, K., Espinosa, R., III, Takeda, J., Le Beau, M. M., and Bell, G. I. (1994). Localization of the kappa opioid receptor gene to human chromosome band 8q11.2. Genomics 19: 596-597.
