Su T H, Wang J C, Tseng H H, Chang C P, Chang T A, Wei H J, Chang J G
Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan.
Int J Cancer. 1998 Apr 13;76(2):216-22. doi: 10.1002/(sici)1097-0215(19980413)76:2<216::aid-ijc8>3.0.co;2-#.
Carcinoma of the uterine cervix is a common malignancy, and many affected women, have been found to exhibit loss of heterozygosity (LOH) in the chromosome 3p region. Recent studies have localized the FHIT (fragile histidine triad) gene in this region and also demonstrated a high frequency of abnormalities of this gene in various cancers. To determine the role of the FHIT gene in cervical and uterine carcinomas, 16 cases of cervical carcinoma and 7 cases of endometrial carcinoma, as well as nearby non-cancerous tissues in these patients, were analyzed by reverse transcription of the FHIT mRNA followed by polymerase chain reaction amplification and sequencing of the products. In this study, 13 of 16 cervical cancers and 4 of 7 endometrial cancers displayed abnormal FHIT transcripts, including a lack of 2 or more exons of the FHIT gene, the insertion of several bases in the deletion junctions, and a 282 bp deletion from cDNA 171 to 452, resulting in a frameshift. Moreover, 5 of 16 matched non-cancerous tissues from the cervical cancer patients and 4 of 7 non-cancerous tissues from endometrial cancer patients also showed the presence of abnormal transcripts lacking 3 or more exons of the FHIT gene. Only 1 of 23 paired samples exhibited LOH. Our results suggest that the abnormal transcript of the FHIT gene is common in both normal and tumor tissues of the uterus and cervix. We also checked for HPV infection in these samples and found no definite relationship between the abnormal transcript and human papillomavirus infection.
子宫颈癌是一种常见的恶性肿瘤,许多患病女性被发现3p染色体区域存在杂合性缺失(LOH)。最近的研究已将FHIT(脆性组氨酸三联体)基因定位在该区域,并且还证明该基因在各种癌症中异常的频率很高。为了确定FHIT基因在子宫颈癌和子宫癌中的作用,通过逆转录FHIT mRNA,然后进行聚合酶链反应扩增和产物测序,对16例子宫颈癌、7例子宫内膜癌以及这些患者的邻近非癌组织进行了分析。在本研究中,16例子宫颈癌中的13例和7例子宫内膜癌中的4例显示FHIT转录本异常,包括FHIT基因缺少2个或更多外显子、缺失连接处插入几个碱基以及cDNA 171至452处有282 bp的缺失,导致移码。此外,16例子宫颈癌患者的配对非癌组织中有5例以及7例子宫内膜癌患者的非癌组织中有4例也显示存在缺少FHIT基因3个或更多外显子的异常转录本。23对样本中只有1对显示杂合性缺失。我们的结果表明,FHIT基因的异常转录本在子宫和子宫颈的正常组织和肿瘤组织中都很常见。我们还检查了这些样本中的HPV感染情况,发现异常转录本与人类乳头瘤病毒感染之间没有明确的关系。