Youk E G, Ku J L, Park J G
Laboratory of Cell Biology, Cancer Research Institute, Seoul National University College of Medicine, Korea.
Dis Colon Rectum. 2001 Feb;44(2):236-42. doi: 10.1007/BF02234299.
Human papillomavirus, particularly Type 16, plays a central role in the development of anogenital squamous-cell carcinomas. A common sequence variation of human papillomavirus Type 16 in cervical cancer cell lines and in cervical cancer tissues from Korean patients was recently reported. The present study was performed to determine the integration type of human papillomavirus DNA in anal epidermoid carcinoma and to identify the common sequence variations in the human papillomavirus Type 16 E7 gene that had been previously reported.
Twenty-one formalin-fixed, paraffin-embedded specimens collected from 29 patients with anal epidermoid carcinomas treated at the Seoul National University Hospital over a ten-year period (1989-1998) were investigated. Genomic DNA from the 21 specimens was extracted and analyzed using the polymerase chain reaction with a general primer and a type-specific primer for human papillomavirus Types 16 and 18. Direct sequencing was performed. As a control, 13 normal anal epithelia available from these patients were microdissected. As another control, 21 hemorrhoidal squamous epithelia obtained from a demographically adjusted group were also analyzed.
Human papillomavirus Type 16 DNA was present in all 21 anal epidermoid carcinomas. All controls were negative for human papillomavirus DNA. Sequence analysis revealed that 57 percent (12/21) specimens showed two types of sequence variation in the E7 gene. One variant with a single nucleotide change at position 647 (amino acid 29, AAT-->AGT, asparagine to serine) was found in 38 percent (8/21) of the samples. This variant has been detected in cervical cancers from Korean patients: 19 (39 percent) of 49 cervical cancer tissues and 6 (50 percent) of 12 cervical cancer cell lines. Another single nucleotide change at position 645 (amino acid 28, TTA-->TTC, leucine to phenylalanine) was found in 19 percent (4/21) of the samples. These two variants exhibit a change of amino acid affecting the critical sites for Rb binding.
Human papillomavirus Type 16 was found to be present in all 21 anal epidermoid carcinomas. Furthermore, in the Korean population, the most common sequence variant found in cervical
人乳头瘤病毒，尤其是16型，在肛门生殖器鳞状细胞癌的发生发展中起核心作用。最近有报道称，在宫颈癌细胞系以及韩国患者的宫颈癌组织中存在人乳头瘤病毒16型的一种常见序列变异。本研究旨在确定肛门表皮样癌中人乳头瘤病毒DNA的整合类型，并鉴定先前报道的人乳头瘤病毒16型E7基因中的常见序列变异。
对首尔国立大学医院在10年期间（1989 - 1998年）收治的29例肛门表皮样癌患者所采集的21份福尔马林固定、石蜡包埋标本进行研究。从这21份标本中提取基因组DNA，并使用针对人乳头瘤病毒16型和18型的通用引物和型特异性引物通过聚合酶链反应进行分析。进行直接测序。作为对照，对从这些患者身上获取的13份正常肛门上皮进行显微切割。作为另一个对照，还对从经过人口统计学调整的群体中获得的21份痔鳞状上皮进行了分析。
21例肛门表皮样癌中均存在人乳头瘤病毒16型DNA。所有对照的人乳头瘤病毒DNA均为阴性。序列分析显示，57%（12/21）的标本在E7基因中呈现两种序列变异类型。在38%（8/21）的样本中发现一种在第647位有单核苷酸变化（氨基酸29，AAT→AGT，天冬酰胺变为丝氨酸）的变异体。在韩国患者的宫颈癌中已检测到这种变异体：49例宫颈癌组织中有19例（39%），12例宫颈癌细胞系中有6例（50%）。在19%（4/21）的样本中发现了另一种在第645位的单核苷酸变化（氨基酸28，TTA→TTC，亮氨酸变为苯丙氨酸）。这两种变异体均表现出影响Rb结合关键位点的氨基酸变化。
在所有21例肛门表皮样癌中均发现人乳头瘤病毒16型。此外，在韩国人群中，在宫颈癌中发现的最常见序列变异……
