ZAC/LOT1在头颈部鳞状细胞癌中的表达缺失。

Loss of expression of ZAC/LOT1 in squamous cell carcinomas of head and neck.

作者信息

Koy Susanne, Hauses Martin, Appelt Hella, Friedrich Katrin, Schackert Hans K, Eckelt Uwe

机构信息

Department of Oral and Maxillofacial Surgery, University Hospital Carl Gustav Carus, Technical University Dresden, Fetscherst. 74, 01307 Dresden, Germany.

出版信息

Head Neck. 2004 Apr;26(4):338-44. doi: 10.1002/hed.10386.

DOI:10.1002/hed.10386

PMID:15054737

Abstract

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.

摘要

背景

ZAC/Lot1是先前鉴定出的候选肿瘤抑制基因。该基因定位于人类6号染色体q24 - q25区域，此区域在头颈部鳞状细胞癌和其他实体瘤中经常缺失。

方法

我们使用头颈部鳞状细胞癌（HNSCC）模型和细胞系来分析候选肿瘤抑制基因ZAC/Lot1在口腔癌发生中的作用。我们分析了11种细胞系中的表达情况，并对51例原发性肿瘤进行了杂合性缺失（LOH）分析和序列分析。

结果

与正常口腔黏膜中该基因的表达水平相比，11种细胞系中有3种（27.3%）显示ZAC/Lot1的表达明显降低。此外，我们用位于ZAC/Lot1两侧的7个微卫星标记对头颈部51例原发性鳞状细胞癌进行了LOH分析。我们在感兴趣区域检测到的平均LOH率为31.4%。序列分析显示ZAC/Lot1编码外显子，包括外显子/内含子边界，没有突变。