This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Takebayashi, S. Articles by Carey, T. E. Search for Related Content PubMed PubMed Citation Articles by Takebayashi, S. Articles by Carey, T. E.

Identification of New Minimally Lost Regions on 18q in Head and Neck Squamous Cell Carcinoma¹

Laboratory of Head and Neck Cancer Biology, The University of Michigan, Ann Arbor, Michigan 48109-0506 [S. T., T. O., K. Y. J., A. M., T. E. C.]; Department of Otorhinolaryngology, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan [H. M.]; Department of Obstetrics and Gynecology, Loyola University, Chicago, Illinois 60153 [S. G. F.]; and Department of Otorhinolaryngology-Head and Neck Surgery, Department of Medical Biochemistry, Turku University, FIN-20521 Turku, Finland [R. G.]

Loss of heterozygosity (LOH) on 18q predicts poor survival in head and neck squamous cell carcinomas (HNSCCs). Several putative tumor suppressor genes, such as DCC, DPC4/Smad4, and MADR2/Smad2, are mapped to 18q, but thus far, the important gene locus in HNSCC is not known. To identify possible gene loci on 18q, we performed LOH studies using tumor DNA from 57 HNSCC primary tumor cell lines and DNA isolated from fibroblasts or lymphoblastoid cells from the same patients. Forty-two highly polymorphic microsatellite markers spaced not more than 5 cM apart (mean distance, 1.82 cM) spanning the region from D18S44 in 18q11.1 to D18S1141 in 18q23 were used. D18S71 in 18p11.21 on 18p was also used to determine whether the short arm was retained. Forty-three of 57 (75%) HNSCC lines showed LOH or isolated allelic imbalance (AI) for at least one locus on 18q. Although many of the cell lines had large distal 18q deletions with a breakpoint between 18q11.1 and 18q12.2 to qter, three loci were identified that were lost in 70% or more of the cases. The minimally lost regions (MLRs) range in size from 1.5–15.79 cM. The most proximal is centered on D18S39 (1.56 cM) in band 18q21.1, with LOH or isolated AI in 28 of 38 (74%) of informative cases. The largest (15.8 cM) begins at D18S61 (28 of 40; 70%) in band 18q22.2 and extends through D18S50 in 18q23. The third is centered on D18S70 (30 of 40; 75%) in band 18q23 (3.67 cM). Of these MLRs, only the one centered on D18S39 has been implicated previously in HNSCC. D18S70, the most frequently lost marker, was the only marker consistently lost in three tumor cell lines with very minimal losses, UM-SCC-19, UM-SCC-67, and UM-SCC-73A. In addition, UM-SCC-91 exhibited AI only at this locus, and UT-SCC-4 had AI at D18S70 and D18S39 only. Close physical mapping of these three regions may pinpoint one or more previously unidentified tumor suppressor genes.

This article has been cited by other articles:

				M. Takkunen, R. Grenman, M. Hukkanen, M. Korhonen, A. Garcia de Herreros, and I. Virtanen Snail-dependent and -independent Epithelial-Mesenchymal Transition in Oral Squamous Carcinoma Cells J. Histochem. Cytochem., November 1, 2006; 54(11): 1263 - 1275. [Abstract] [Full Text] [PDF]

				B. S. Henson, R. R. Neubig, I. Jang, T. Ogawa, Z. Zhang, T. E. Carey, and N. J. D'Silva Galanin Receptor 1 Has Anti-proliferative Effects in Oral Squamous Cell Carcinoma J. Biol. Chem., June 17, 2005; 280(24): 22564 - 22571. [Abstract] [Full Text] [PDF]

				A. Baez, A. Cantor, S. Fonseca, M. Marcos-Martinez, L. A. Mathews, C. A. Muro-Cacho, and T. Munoz-Antonia Differences in Smad4 Expression in Human Papillomavirus Type 16-Positive and Human Papillomavirus Type 16-Negative Head and Neck Squamous Cell Carcinoma Clin. Cancer Res., May 1, 2005; 11(9): 3191 - 3197. [Abstract] [Full Text] [PDF]

				J. Akervall, X. Guo, C.-N. Qian, J. Schoumans, B. Leeser, E. Kort, A. Cole, J. Resau, C. Bradford, T. Carey, et al. Genetic and Expression Profiles of Squamous Cell Carcinoma of the Head and Neck Correlate with Cisplatin Sensitivity and Resistance in Cell Lines and Patients Clin. Cancer Res., December 15, 2004; 10(24): 8204 - 8213. [Abstract] [Full Text] [PDF]

				M. A. Ginos, G. P. Page, B. S. Michalowicz, K. J. Patel, S. E. Volker, S. E. Pambuccian, F. G. Ondrey, G. L. Adams, and P. M. Gaffney Identification of a Gene Expression Signature Associated with Recurrent Disease in Squamous Cell Carcinoma of the Head and Neck Cancer Res., January 1, 2004; 64(1): 55 - 63. [Abstract] [Full Text] [PDF]

				C. R. Bradford Genetic Markers of Head and Neck Cancer: Identifying New Molecular Targets Arch Otolaryngol Head Neck Surg, March 1, 2003; 129(3): 366 - 367. [Full Text] [PDF]

				D J Smiraglia, L T Smith, J C Lang, L J Rush, Z Dai, D E Schuller, and C Plass Differential targets of CpG island hypermethylation in primary and metastatic head and neck squamous cell carcinoma (HNSCC) J. Med. Genet., January 1, 2003; 40(1): 25 - 33. [Abstract] [Full Text] [PDF]

				M. P. Tabor, R. H. Brakenhoff, V. M. M. van Houten, J. A. Kummer, M. H. J. Snel, P. J. F. Snijders, G. B. Snow, C. R. Leemans, and B. J. M. Braakhuis Persistence of Genetically Altered Fields in Head and Neck Cancer Patients: Biological and Clinical Implications Clin. Cancer Res., June 1, 2001; 7(6): 1523 - 1532. [Abstract] [Full Text] [PDF]

				C. A. Muro-Cacho, K. Rosario-Ortiz, S. Livingston, and T. Munoz-Antonia Defective Transforming Growth Factor {beta} Signaling Pathway in Head and Neck Squamous Cell Carcinoma as Evidenced by the Lack of Expression of Activated Smad2 Clin. Cancer Res., June 1, 2001; 7(6): 1618 - 1626. [Abstract] [Full Text] [PDF]