Analysis of HPV-positive and -negative vulvar carcinomas for alterations in c-myc, Ha-, Ki-, and N-ras genes.

Analysis of HPV-positive and -negative vulvar carcinomas for alterations in c-myc, Ha-, Ki-, and N-ras genes.
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分析 HPV 阳性和阴性外阴癌的 c-myc、Ha-、Ki- 和 N-ras 基因的变化。

DOI:
10.1006/gyno.1994.1091
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发表时间:
1994
影响因子:
4.7
通讯作者:
C. Crum
C. Crum
中科院分区:
医学2区
文献类型:
--
作者:
J. Tate;G. Mutter;C. Prasad;R. Berkowitz;H. Goodman;C. Crum

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某些宿主基因(包括 c-myc、Ha-ras 和 Ki-ras)的突变或过度表达与生殖器鳞状肿瘤(特别是子宫颈)相关,并且与这些肿瘤的自然史有关。这些宿主基因改变与外阴鳞状细胞癌的关系以前尚未研究过。我们使用基于 PCR 的检测方法分析了 13 例人乳头瘤病毒阳性和阴性外阴鳞状细胞癌的档案材料中 Ha-、Ki- 和 N-ras 基因的突变,以及少量新鲜样本的 c-myc 扩增。为了进行比较,还分析了八个宫颈鳞状细胞癌(三个固定的和五个新鲜的)。 ras 突变分析揭示了先前报道的 Ha-ras 基因中核苷酸 1744 处的沉默等位基因变异,但密码子 12、13 或 61 中没有突变。同样,在这些病例中也没有发现超过最多三个单倍体拷贝的 c-myc 基因组扩增。这些发现表明,myc 或 ras 序列的改变与外阴鳞状细胞癌或 HPV 核酸的存在或缺失无关。此外,他们显然无法区分外阴癌和宫颈癌,两组似乎不太可能存在这些序列改变。
Mutation or overexpression of certain host genes, including c-myc, Ha-ras, and Ki-ras, have been associated with genital squamous neoplasia, specifically in the cervix, and have been implicated in the natural history of these tumors. The relationship of these host gene alterations to vulvar squamous cell carcinomas has not been previously studied. We analyzed archival material from 13 human papillomavirus-positive and -negative vulvar squamous cell carcinomas for mutations in Ha-, Ki-, and N-ras genes, and a smaller number of fresh samples for c-myc amplification, using PCR-based assays. For comparison, eight cervical squamous cell carcinomas (three fixed and five fresh) were also analyzed. Analysis for ras mutations revealed a previously reported silent allelic variant at nucleotide 1744 in the Ha-ras gene, but no mutations in codons 12, 13, or 61. Similarly, genomic amplification of c-myc beyond a maximum of three haploid copies was not identified in the cases. These findings indicate that alterations in myc or ras sequences are not linked to vulvar squamous cell carcinomas or to the presence or absence of HPV nucleic acids. Moreover, they apparently will not distinguish vulvar from cervical carcinomas, both groups appearing to be unlikely to harbor these sequence alterations.