MUTATIONS, EXPRESSION AND GENOMIC INSTABILITY OF THE H-RAS PROTOONCOGENE IN SQUAMOUS-CELL CARCINOMAS OF THE HEAD AND NECK

被引:95
作者
KIARIS, H
SPANDIDOS, DA
JONES, AS
VAUGHAN, ED
FIELD, JK
机构
[1] UNIV LIVERPOOL, SCH DENT, DEPT CLIN DENT SCI, MOLEC GENET & ONCOL GRP, LIVERPOOL L69 3BX, MERSEYSIDE, ENGLAND
[2] UNIV CRETE, SCH MED, IRAKLION, GREECE
[3] NATL HELLEN RES FDN, INST BIOL RES & BIOTECHNOL, GR-11635 ATHENS, GREECE
[4] UNIV LIVERPOOL, DEPT OTORHINOLARYNGOL, LIVERPOOL L69 3BX, MERSEYSIDE, ENGLAND
[5] WALTON HOSP, MAXILLOFACIAL UNIT, LIVERPOOL L9 1AE, MERSEYSIDE, ENGLAND
关键词
RAS MUTATIONS; H-RAS EXPRESSION; SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK; ORAL CANCER;
D O I
10.1038/bjc.1995.287
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Mutation and overexpression are the main activating mechanisms for the ras family of genes in human cancer and the variable tandem repeat (VTR) located at the 3' end of H-ras has been associated with this risk. In the present study, we have analysed the relative levels of expression of H-ras mRNA in 26 samples of squamous cell carcinomas of the head and neck (SCCHN) by competitive reverse transcription-polymerase chain reaction (competitive RT-PCR) and also investigated whether there is an association between ras expression acid alterations in the 3'-VTR region. In addition, we have studied the incidence of point mutations in codon 12 of H-ras, codons 12 and 13 of K-ras and codon 61 of N-ras in 120 SCCHN samples. Our results indicate that only two samples carry mutations, both of which are located in codon 12 of K-ras, but that overexpression of the H-ras proto-oncogene is a frequent event in SCCHN [54% (14/26)] and is associated with a favourable prognosis: 3 of 14 patients with H-ras overexpression have died, whereas 9 of 12 patients with low levels of H-ras expression have died. We have also undertaken an analysis of these results together with our previous investigations on microsatellite instability and loss of heterozygosity in SCCHN, but no associations were found. We therefore conclude that ras mutations are an infrequent event in the progression of the SCCHN in the Western world, whereas overexpression of the H-ras proto-oncogene is a common event.
引用
收藏
页码:123 / 128
页数:6
相关论文
共 37 条
[1]  
Azuma M, 1987, CANCER J, V1, P375
[2]   RAS GENES [J].
BARBACID, M .
ANNUAL REVIEW OF BIOCHEMISTRY, 1987, 56 :779-827
[3]   PROTEINS REGULATING RAS AND ITS RELATIVES [J].
BOGUSKI, MS ;
MCCORMICK, F .
NATURE, 1993, 366 (6456) :643-654
[4]  
BOS JL, 1989, CANCER RES, V49, P4682
[5]  
BREATHNACH R, 1981, ANNU REV BIOCHEM, V50, P349, DOI 10.1146/annurev.bi.50.070181.002025
[6]   RAS MUTATIONS IN UNITED-KINGDOM EXAMPLES OF ORAL MALIGNANCIES ARE INFREQUENT [J].
CHANG, SE ;
BHATIA, P ;
JOHNSON, NW ;
MORGAN, PR ;
MCCORMICK, F ;
YOUNG, B ;
HIORNS, L .
INTERNATIONAL JOURNAL OF CANCER, 1991, 48 (03) :409-412
[7]   THE ABSENCE OF HARVEY RAS MUTATIONS DURING DEVELOPMENT AND PROGRESSION OF SQUAMOUS-CELL CARCINOMAS OF THE HEAD AND NECK [J].
CLARK, LJ ;
EDINGTON, K ;
SWAN, IRC ;
MCLAY, KA ;
NEWLANDS, WJ ;
WILLS, LC ;
YOUNG, HA ;
JOHNSTON, PW ;
MITCHELL, R ;
ROBERTSON, G ;
SOUTAR, D ;
PARKINSON, EK ;
BIRNIE, GD .
BRITISH JOURNAL OF CANCER, 1993, 68 (03) :617-620
[8]   OVEREXPRESSION OF C-K-RAS, C-N-RAS AND TRANSFORMING GROWTH-FACTOR-BETA CO-SEGREGATE WITH TUMORIGENICITY IN MORPHOLOGICALLY TRANSFORMED C3H-10T1/2 CELL-LINES [J].
COLEMAN, WB ;
THRONEBURG, DB ;
GRISHAM, JW ;
SMITH, GJ .
CARCINOGENESIS, 1994, 15 (05) :1005-1012
[9]  
Field J K, 1992, Eur J Cancer B Oral Oncol, V28B, P67, DOI 10.1016/0964-1955(92)90016-T
[10]  
FIELD JK, 1990, ANTICANCER RES, V10, P1