Loss of expression of ZAC/LOT1 in squamous cell carcinomas of head and neck.
BACKGROUND
ZAC/Lot1 is a previously identified candidate tumor suppressor gene. The gene maps to the human chromosome 6q24-q25, a region frequently deleted in squamous cell carcinomas of the head and neck and other solid tumors.


METHODS
We have used a model of head and neck squamous cell carcinoma (HNSCC) and cell lines to analyze the role of the candidate tumor suppressor gene ZAC/Lot1 in oral carcinogenesis. We analyzed the expression in 11 cell lines, and we performed loss of heterozygosity (LOH)- and sequence analyses in 51 primary tumors.


RESULTS
Three (27.3%) of 11 cell lines showed a distinctly reduced expression of ZAC/Lot1 compared with expression levels of the gene in the normal oral mucosa. In addition, we analyzed 51 primary squamous cell carcinomas of the head and neck for LOH with seven microsatellite markers flanking ZAC/Lot1. We detected an average LOH rate of 31.4% in the region of interest. Sequence analysis revealed no mutations for the ZAC/Lot1 coding exons, including the exon/intron boundaries.


CONCLUSIONS
These data could suggest a minimal role for ZAC/Lot1 in a subgroup of HNSCC tumors.
Koy
Susanne
S
Department of Oral and Maxillofacial Surgery, University Hospital Carl Gustav Carus, Technical University Dresden, Fetscherst. 74, 01307 Dresden, Germany.
Hauses
Martin
M
Appelt
Hella
H
Friedrich
Katrin
K
Schackert
Hans K
HK
Eckelt
Uwe
U
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D008954:Models, Biological; D009061:Mouth Mucosa / Q000378:metabolism; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics*; D025521:Tumor Suppressor Proteins
D018797:Cell Cycle Proteins; D004273:DNA, Neoplasm; C106464:PLAGL1 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins