Molecular characterization of head and neck tumors by analysis of telomerase activity and a panel of microsatellite markers.
Head and neck cancer is a frequent malignancy with a complex, and up to now not clear etiology. The reactivation of telomerase activity and losses or gains of specific chromosomal regions, which point to deletions of tumor suppressor genes or amplification of oncogenes are supposed to be the molecular processes during the development and progression of head and neck cancer. Therefore, we analyzed telomerase activity and microsatellite markers using a genome wide panel of 28 microsatellite markers in 38 head and neck squamous-cell carcinomas (HNSCC). Our microsatellite marker set included distinct chromosomal areas that all likely harbor genes contributing to the carcinogenesis of HNSCC. DNA or protein lysates were obtained from primary tumors and compared to peripheral lymphocytes or corresponding normal tissue. At least one genomic alteration [loss of heterozygosity (LOH), or microsatellite instability (MSI)] was found in 31 of the 38 cases (82%). Most frequently we detected an LOH in the chromosomal region 9p12-21 where at least the tumor suppressor genes (TSG) p16INK4A, p14ARF and p15INKB are localized. The comparison between grade two and grade three tumors showed a highly changed frequency of LOH in the chromosomal region 7q31, where a putative TSG is predicted. Telomerase activity was present in 31/37 (83.8%) tumor samples independent of the histopathological staging and grading of the tumors. These molecular characterizations of HNSCC may be a further hint for the involvement of additional, so far unknown, TSGs in the tumor progression and will elucidate the regulation of telomerase.
Fiedler
Wolfgang
W
Institute of Human Genetics and Anthropology, Friedrich-Schiller-University, D-07740 Jena, Germany.
Hoppe
Constance
C
Schimmel
Bettina
B
Koscielny
Sven
S
Dahse
Regine
R
Bereczki
Zsuzsa
Z
Claussen
Uwe
U
Ernst
Günther
G
von Eggeling
Ferdinand
F
D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism; D005819:Genetic Markers; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics; D008214:Lymphocytes / Q000378:metabolism; D018895:Microsatellite Repeats / Q000235:genetics*; D019098:Telomerase / Q000378:metabolism*
D005819:Genetic Markers; D019098:Telomerase