Objective: Overrepresentations of chromosomal material on the long arm of chromosome 3 frequently occur in squamous cell carcinoma of the head and neck. This experimental study was conducted for further fine mapping of these overrepresentations by interphase fluorescence in situ hybridization (FISH) of tumor cells in cell lines. Methods: Seven cell lines derived from squamous cell carcinomas of the head and neck were investigated by comparative genomic hybridization to analyze unbalanced chromosomal aberrations. Overrepresentations of chromosomal material on the telomeric part of the long arm of chromsome 3 were further analyzed by interphase FISH using YAC contig clones. Results: Chromosomal aberrations which frequently occurred were overrepresentations on 5p (n = 4), 7p (n = 5), 11q13 (n = 3), 15q (n = 5), 17q (n = 3), 19q (n = 2), 20q (n = 2) and 22q (n = 3). Reoccurring losses of chromosomal material were found in 3p (n = 3), 7q (n = 2), 18q (n = 3) and 19p (n = 2). Gains of chromosomal material on chromosome 3q were found in 4 out of 7 cell lines, with a high copy number of amplifications occurring in the chromosomal region of 3q26.3–28. Further experiments revealed a physical mapping of this amplification to a narrow band of 13.8 Mbp on chromosome 3q, whose amplification borders were represented by the YAC clones 754_f_3 centomeric and 955_b_2 telomeric. Conclusions: By FISH, the amplification of chromosomal material on 3q could be fine mapped on a narrow band on 3q26.3–27. This aberration can be considered as a breakpoint in tumorigenesis. Putative candidate oncogenes and tumor suppressor genes located in this region might be a target for mutations leading to tumor progression.

1.
Carey TE, Van Dyke DL, Worsham MJ: Nonrandom chromosome aberrations and clonal populations in head and neck cancer. Anticancer Res 1993;13:2561–2568.
2.
Van Dyke DL, Worsham MJ, Beninger MS, et al: Recurrent cytogenetic abnormalities in squamous cell carcinoma of the head and neck region. Genes Chromosomes Cancer 1994;9:192–206.
3.
Sidransky D: Molecular markers in cancer: Can we make better predictions? Int J Cancer 1995;64:1–2.
4.
Bockmuhl U, Schwendel A, Dietel M, Petersen I: Distinct patterns of chromosomal alterations in high- and low-grade head and neck squamous cell carcinomas. Cancer Res 1996;56:5325–5329.
5.
Heselmeyer K, Schrock E, du Manoir S, Blegen H, Shah K, Steinbeck R, Auer G, Ried T: Gain of chromosome 3q defines the transition from severe dysplasia to invasive carcinoma of the uterine cervix. Proc Natl Acad Sci USA 1996;93:479–484.
6.
Heselmeyer K, Macville M, Schrock E, Blegen H, Hellstrom AC, Shah K, Auer G, Ried T: Advanced-staged cervical carcinomas are defined by a recurrent pattern of chromosomal aberrations revealing high genetic instability and a consistent gain of chromosome arm 3q. Genes Chromosomes Cancer 1997;19:233–240.
7.
Carey TE: Establishment of Epidermoid Carcinoma Cell Lines. Dordrecht, Kluwer Academic, 1991, pp 287–314.
8.
Telenius H, Carter NP, Bebb CE, Nordenskjold T, Ponder BA, Tunnacliffe A: Degenerate oligonucleotide-primed PCR: General amplification of target DNA by a single degenerate primer. Genomics 1992;13:718–725.
9.
Welkoborsky HJ, Jacob R, Riazimand SH, Bernauer HS, Mann WJ, Carey TE: Cytogenetical, immunohistochemical and cytometrical characterization of seven new cell lines of squamous cell carcinomas of the head and neck. Laryngoscope, submitted.
10.
Du Manoir S, Schröck E, Bentz M, Speicher MR, Joos S, Ried T, Lichter P, Cremer T: Quantitative analysis of comparative genomic hybridization. Cytometry 1995;19:27–41.
11.
Hermsen MAJA, Joenje H, Arwert F, Welters MJP, Braakhuis BJM, Bagnay M, Westerveld A, Slater R: Centromeric breakage as a major cause of cytogenetic abnormalities in oral squamous cell carcinomas. Genes Chromosomes Cancer 1996;15:1–9.
12.
Bergamo NA, Rogatto SR, Poli-Frederico RC, Reis PP, Kowalski LP, Zielenska M, Squire JA: Comparative genomic hybridization analysis detects frequent over-representation of DNA sequences at 3q, 7p and 8q in head and neck carcinomas. Cancer Genet Cytogenet 2000;119:48–55.
13.
Bockmühl U, Petersen S, Schmidt S, Wolf G, Jahnke V, Dietel M, Petersen I: Patterns of chromosomal alterations in metastasizing and non-metastasizing primary head and neck carcinomas. Cancer Res 1997;57:5213–5216.
14.
Welkoborsky HJ, Bernauer HS, Riazimand HS, Jacob R, Mann WJ, Hinni ML: Pattern of chromosomal aberrations in metastasizing and non-metastasizing squamous cell carcinomas of the oro- and hypopharynx. Ann Otol Rhinol Laryngol 2000;110:401–410.
15.
Speicher M, Howe C, Crotty P, du Manoir S, Costa J, Ward D: Comparative genomic hybridization detects novel deletions and amplifications in head and neck squamous cell carcinomas. Cancer Res 1995;55:1010–1013.
16.
Brzoska P, Levin NA, Fu KK, Kaplan MJ, Singer MI, Gray JW, Christman MF: Frequent novel DNA copy number increase in squamous cell head and neck tumors. Cancer Res 1995;55:3055–3059.
17.
Bjorkqvist AM, Husgafvel-Pursiainen K, Anttila S, Karjaleinen A, Tammilehto L, Mattson K, Vainio H, Knuutila S: DNA gains in 3q occur frequently in squamous cell carcinoma of the lung, but not in adenocarcinoma. Genes Chromosomes Cancer 1998;22:79–82.
18.
Weber RG, Scheer M, Born IA, Joos S, Cobbers JM, Hofele C, Reifenberger G, Zoller JE, Lichter P: Reccurrent chromosomal imbalances detected in biopsy material from oral premalignant and malignant lesions by combined tissue microdissection, universal DNA amplification, and comparative genomic hybridization. Am J Pathol 1998;153:295–303.
19.
Jin C, Jin Y, Wennerberg J, Dictor M, Mertens F: Nonrandom pattern of cytogenetic abnormalities in squamous cell carcinoma of the larynx. Genes Chromosomes Cancer 2000;28:66–76.
20.
Oga A, Kong G, Tae K, Lee Y, Sasaki K: Comparative genomic hybridization analysis reveals 3q gain resulting in genetic alteration in 3q in advanced oral squamous cell carcinoma. Cancer Genet Cytogenet 2001;127:24–29.
21.
Brass N, Heckel D, Sahin U, Pfreundschuh M, Sybrecht GW, Meese E: Translation initiation factor elF-4gamma is encoded by an amplified gene and induces an immune response in squamous cell lung carcinoma. Hum Mol Genet 1997;6:33–39.
22.
Levin NA, Brzoska PM, Warnock ML, Gray JW, Christman MF: Identification of novel regions of altered DNA copy number in small cell lung tumors. Genes Chromosomes Cancer 1995;13:175–185.
23.
Kettunen E, el-Rifai W, Bjorkqvist AM, Wolff H, Karjalainen A, Antia S, Mattson K, Husgafvel-Pursiainen K, Knuutila S: A broad amplification pattern at 3q in squamous cell lung cancer – a fluorescence in situ hybridization study. Cancer Genet Cytogenet 2000;117:66–70.
24.
Sugita M, Tanaka N, Davidson S, Sekiya S, Varella-Garcia M, West J, Drabkin HA, Gemmill RM: Molecular definition of a small amplification domain within 3q26 in tumors of the cervix, ovary and lung. Cancer Genet Cytogenet 2000;117:9–18.
25.
Sreekantaiah C, Rao PH, Xu L, Sacks PG, Schantz SP, Chaganti RS: Consistent chromosomal losses in head and neck squamous cell carcinoma cell lines. Genes Chromosomes Cancer 1994;11:29–39.
26.
Thein AT, Han X, Heyderman E, Fox M, Steele SJ, Parrington JM: Molecular cytogenetic analysis of five newly established cervical cancer lines using G banding and fluorescence in situ hybridization. Cancer Genet Cytogenet 1996;91:28–36.
27.
Komiyama T, Matsumura K, Tsuchida N: Comparison of DNA copy numbers in original oral squamous cell carcinomas and corresponding cell lines by comparative genomic hybridization. Jpn J Cancer Res 1997;88:476–483.
28.
Lydiatt WM, Davidson BJ, Schantz SP, Caruana S, Chaganti RS: 9p21 deletion correlates with recurrence in head and neck cancer. Head Neck 1998;20:113–118.
29.
Miracca EC, Yamamoto L, Contado D, de Souza Silva Takimoto M, Kowalski LP, Nagai MA: Distinct chromosomal deleted regions defining different subsets of head and neck tumors. Diagn Mol Pathol 2000;9:229–233.
30.
Yamane K, Kawabata M, Tsuruo T: A DNA-topoisomerase-II-binding protein with eight repeating regions similar to DNA repair enzymes and to cell cycle regulator. Eur J Biochem 1997;250:794–799.
31.
Westwick JK, Lee RJ, Lambert QT, Symons M, Pestell RG, Der CJ, Whitehead IP: Transforming potential of Dbl family proteins correlates with transcription from the cyclin D1 promoter but not with activation of Jun NH2-terminal kinase, p38/Mpk2, serum response factor, or c-Jun. J Biol Chem 1998;273:16739–16747.
32.
Volinia S, Hiles I, Ormondroyd E, Nizetic D, Antonacci R, Rocchi M, Waterfield MD: Molecular cloning, cDNA sequence, and chromosomal localization of the human phosphatidylinositol 3-kinase p110 alpha (PIK3CA) gene. Genomics 1994;24:472–477.
33.
Yang Y, Lijam N, Sussman DJ, Tsang M: Genomic organization of mouse Dishevelled genes. Gene 1996;21:121–123.
34.
Tsang M, Lijam N, Yang Y, Beier DR, Wynshaw-Boris A, Sussman DJ: Isolation and characterization of mouse dishevelled-3. Dey Dyn 1996;207:253–262.
35.
Yi J, Beckerle MC: The human TRIP6 gene encodes a LIM domain protein and maps to chromosome 7q22, a region associated with tumorigenesis. Genomics 1998;49:314–316.
36.
Chen W, Iida S, Louie DC, Dalla-Favera R, Chaganti RS: Heterologous promoters fused to Bcl6 by chromosomal translocations affecting band 3q27 cause its deregulated expression during B-cell differentiation. Blood 1998;91:603–607.
37.
Ohno H, Fukuhara S: Significance of rearrangement of the Bcl6 gene in B-cell lymphoid neoplasms. Leuk Lymphoma 1997;27:53–63.
38.
Deweindt C, Albagli O, Bernardin F, Dhordain R, Quief S, Lantoine D, Kerckaert JP, Leprince D: The LAZ3/Bcl6 oncogene encodes a sequence-specific transcriptional inhibitor: A novel function for the BTB/POZ domain as an autonomous repressing domain. Cell Growth Differ 1995;6:1495–1503.
39.
Cullmann G, Fien K, Kobayashi R, Stillman B: Characterization of the five replication factor C genes of Saccharomyces cerevisiae. Mol Cell Biol 1995;15:4661–4671.
40.
Azim AC, Knoll JH, Marfatia SM, Peel DJ, Bryant PJ, Chishti AH: DLG1: Chromosome location of the closest human homologue of the Drosophila discs large tumor suppressor gene. Genomics 1995;30:613–616.
41.
Craig AW, Haghighat A, Yu AT, Sonenberg N: Interaction of polyadenylate-binding protein with the elF4A homologue PAIP enhances translation. Nature 1998;392:520–523.
42.
Reubi JC, Schaer JC, Waser B, Hoeger C, Rivier J: A selective analog for the somatostatin sst1-receptor subtype expressed by human tumors. Eur J Pharmacol 1998;345:103–110.
43.
Sharma K, Srikant CB: Induction of wild-type p53, Bax, and acidic endonuclease during somatostatin-signaled apoptosis in MCF-7 human breast cancer. Int J Cancer 1998;76:259–266.
44.
Yamaguchi K, Wu L, Caballero OL, Hibi K, Trink B, Resto V, Cairns P, Okami K, Koch WM, Sidransky D, Jen J: Frequent gain of the p40/p51/p63 gene locus in primary head and neck squamous cell carcinoma. Int J Cancer 2000;86:684–689.
45.
Hibi K, Trink B, Patturajan M, Westra WH, Caballero OL, Hill DE, Ratovitski EA, Jen J, Sidransky D: AIS is an oncogene amplified in squamous cell carcinoma. Proc Natl Acad Sci USA 2000;97:5462–5467.
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