Tandle A, Sanghavi V, Saranath D
Laboratory of Cancer Genes, Cancer Research Institute, Tata Memorial Hospital, Tata Memorial Centre, Parel, 400 012, Mumbai, India.
Cancer Lett. 2000 Sep 1;157(2):155-60. doi: 10.1016/s0304-3835(00)00484-5.
We have investigated loss of heterozygosity (LOH) of the adenomatous polyposis coli (APC) tumor suppressor gene using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) in 86 untreated oral cancer patients, using matched oral cancer tissue and corresponding peripheral blood cell (PBC) DNA samples. PBC from 70 normal healthy individuals, were also analyzed for allelic distribution of APC gene. A 133 bp fragment, spanning exon 11 of the APC gene was amplified, and RsaI digestion of the PCR product defined the alleles as either homozygous 133 bp (Rsa(-/-)) or 87 and 46 bp (Rsa(+/+)) fragments, and heterozygous (Rsa(+/-)) exhibiting the three fragments. Distribution of the three alleles, Rsa(-/-), Rsa(+/+), and Rsa(+/-) in the oral cancer patients was observed as 10.5, 51.1 and 38.4%; whereas normal healthy individuals showed 11.4, 37.1 and 51.4%, respectively. In the informative heterozygous (Rsa(+/-)) oral cancer patients, LOH was infrequent, demonstrated in two of 33 (6%) samples. Thus, the APC gene was infrequently altered by LOH at the polymorphic RsaI locus in exon 11 in the tobacco associated Indian oral cancer, unlike the smoking tobacco/alcohol associated oral cancers from Western countries.
我们使用聚合酶链反应(PCR)-限制性片段长度多态性(RFLP)技术,对86例未经治疗的口腔癌患者的腺瘤性息肉病(APC)肿瘤抑制基因杂合性缺失(LOH)进行了研究,采用配对的口腔癌组织和相应的外周血细胞(PBC)DNA样本。还对70名正常健康个体的PBC进行了APC基因等位基因分布分析。扩增了一个跨越APC基因第11外显子的133 bp片段,PCR产物经RsaI酶切后,等位基因被定义为纯合的133 bp(Rsa(-/-))或87和46 bp(Rsa(+/+))片段,杂合子(Rsa(+/-))则呈现这三种片段。在口腔癌患者中,Rsa(-/-)、Rsa(+/+)和Rsa(+/-)这三种等位基因的分布分别为10.5%、51.1%和38.4%;而正常健康个体分别为11.4%、37.1%和51.4%。在信息性杂合(Rsa(+/-))的口腔癌患者中,LOH并不常见,33个样本中有2个(6%)出现了LOH。因此,与西方国家吸烟/饮酒相关的口腔癌不同,在印度与烟草相关的口腔癌中,APC基因在第11外显子的多态性RsaI位点很少因LOH而改变。