Yoshino K, Enomoto T, Nakamura T, Nakashima R, Wada H, Saitoh J, Noda K, Murata Y
Department of Obstetrics and Gynecology, Osaka University Faculty of Medicine, Japan.
Int J Cancer. 1998 Apr 13;76(2):176-81. doi: 10.1002/(sici)1097-0215(19980413)76:2<176::aid-ijc2>3.0.co;2-u.
The fragile histidine triad (FHIT) tumor suppressor gene at 3p14.2 has abnormalities in several types of human cancers. To investigate the potential role of FHIT in cervical cancer, which exhibits frequent loss of heterozygosity of 3p, we have examined primary cervical cancer samples from 28 patients for alterations of the FHIT gene. Abnormal FHIT transcripts were detected using reverse transcription-polymerase chain reaction (PCR) and subsequently by sequencing. Of 28 primary cervical carcinomas analyzed, 12 tumors (43%) showed abnormal FHIT transcripts, including deletion, insertion and point mutation. Loss of a FHIT transcript was observed in 2 cases (7%). Allelic loss of the FHIT gene was detected in 16 of 27 informative cases (59%). Oncogenic human papillomavirus (HPV) type 16, 18, 33, 35, 58 and 59 were not only present but were expressed in 24 of 28 cases (85%) by consensus PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) analysis for the HPV E6 and E7 genes. Our data indicate that alteration of the FHIT gene is an important genetic event associated with cervical cancer and oncogenic
位于3p14.2的脆性组氨酸三联体（FHIT）肿瘤抑制基因在几种类型的人类癌症中存在异常。为了研究FHIT在宫颈癌中的潜在作用，宫颈癌常出现3p杂合性缺失，我们检测了28例患者的原发性宫颈癌样本中FHIT基因的改变。使用逆转录-聚合酶链反应（PCR）检测异常的FHIT转录本，随后进行测序。在分析的28例原发性宫颈癌中，12例肿瘤（43%）显示FHIT转录本异常，包括缺失、插入和点突变。2例（7%）观察到FHIT转录本缺失。在27例信息充分的病例中，16例（59%）检测到FHIT基因的等位基因缺失。通过对HPV E6和E7基因进行一致性PCR-RFLP（聚合酶链反应-限制性片段长度多态性）分析，发现致癌性人乳头瘤病毒（HPV）16、18、33、35、58和59型不仅存在，而且在28例中的24例（85%）中表达。我们的数据表明，FHIT基因的改变是与宫颈癌和致癌作用相关的重要遗传事件。
