Delineation and candidate gene mutation screening of the 18q22 minimal region of deletion in head and neck squamous cell carcinoma

被引:20
作者
Blons, H
Laccourreye, O
Houllier, AM
Carnot, F
Brasnu, D
Beaune, P
Zucman-Rossi, J
Laurent-Puig, P
机构
[1] INSERM, U490, Unite Toxicol Mol, Mol Toxicol Lab, F-75006 Paris, France
[2] Assistance Publ Hop Paris, Hop Europeen Georges Pompidou, Serv Otorhinolaryngol & Chirurg Cervicofaciale, F-75015 Paris, France
[3] Assistance Publ Hop Paris, Hop Europeen Georges Pompidou, Lab Anatomopathol, F-75015 Paris, France
[4] Ctr Etud Polymorphisme Humain, INSERM, U434, F-75010 Paris, France
关键词
head and neck neoplasm; chromosome; 18; tumor suppressor gene; allelic losses; mutations; dHPLC;
D O I
10.1038/sj.onc.1205626
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The 18q chromosome arm is frequently lost in advanced head and neck squamous cell carcinoma. Twenty-four microsatellite markers located on chromosome 18q were genotyped in 145 primary tumors and 10 cell lines in order. to identify putative tumor suppressor genes implicated in tumor progression. Two different minimal common regions of loss (MCRL) were identified at 18q22 and l8q23 respectively. To refine and delineate boundaries of an homozygous deletion found in one cell line, 44 extra markers located at 18q22 were analysed and the homozygous deletion was precisely defined within a critical region of 4.9 Mb. Four known genes (CDH7, CDH19, DNAM-1, FLJ23594) located in this critical region and two EST clusters (Hs.96900, Hs.98628) were selected for further investigations. For these six genes, genomic structures were established, somatic mutations were screened in 20 HNSCC and 10 cell lines and transcription levels were determined in eight cell lines. No somatic mutations were found in any of the candidate genes analysed (57 coding exons). However, differential transcription levels were observed for CDH19 and Hs.96900 in head and neck cancer cell lines supporting their putative involvement through down regulation mechanisms in head and neck cancer progression.
引用
收藏
页码:5016 / 5023
页数:8
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