Mutations of the adenomatous polyposis coli gene in sporadic thyroid neoplasms.
Mutations of the adenomatous polyposis coli gene in sporadic thyroid neoplasms.
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DOI：
10.1210/jcem.79.5.7962323
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发表时间：
1994-11
期刊：
影响因子：
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通讯作者：
K. Zeki;D. Spambalg;Nazy Sharifi;R. Gonsky;J. Fagin
中科院分区：
文献类型：
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作者：
K. Zeki;D. Spambalg;Nazy Sharifi;R. Gonsky;J. Fagin
几项流行病学研究表明家族性腺瘤性大肠息肉病（FAP）与甲状腺肿瘤之间存在关联。FAP的易感性是由位于染色体5q21上的APC基因突变引起的。大约60%的散发性结直肠腺瘤和癌中也观察到APC的体细胞突变，这表明这种假定的肿瘤抑制基因的破坏可能在家族性和获得性结直肠肿瘤发生中发挥作用。APC基因在正常人甲状腺、甲状腺腺瘤、分化癌组织以及四种克隆性人甲状腺癌细胞系中均有表达，通过逆转录-聚合酶链反应证明了横跨14和15外显子的388碱基APC信使核糖核酸片段，然后与15外显子特异性互补DNA探针杂交。使用紧靠APC基因的高变二核苷酸（CA）重复序列（CB26）的引物，检测80例人甲状腺肿瘤APC基因座杂合性缺失。在71%的信息样本中，2例显示等位基因丢失：滤泡性腺瘤（FA）和多结节性甲状腺肿（MNG）的结节。采用单链构象多态性检测83例甲状腺良、恶性肿瘤和4例甲状腺癌细胞系的DNA在第15外显子1200碱基对内的突变。采用5组重叠引物进行PCR。甲状腺间变性癌细胞系（ARO）有1个APC等位基因，在1556密码子（ACTA to AACTA）上有腺嘌呤插入，导致1558密码子过早终止。间变性癌具有密码子1346 （TCA-CCA; Ser - to - Pro）突变。总之，APC基因在正常和肿瘤人甲状腺组织中表达，是一些甲状腺肿瘤灭活突变的靶标。
Several epidemiological studies have demonstrated an association between familial adenomatous polyposis coli (FAP) and thyroid neoplasms. Predisposition to FAP is conferred by mutations in the APC gene, located on chromosome 5q21. Somatic mutations of APC are also observed in about 60% of sporadic colorectal adenomas and carcinomas, suggesting that disruption of this putative tumor suppressor gene may play a role in both familial as well as acquired colorectal tumorigenesis. The APC gene is expressed in normal human thyroid, thyroid adenomas, and differentiated carcinoma tissues as well as in four clonal human thyroid carcinoma cell lines, as demonstrated by reverse transcriptase-polymerase chain reaction of a 388-base APC messenger ribonucleic acid fragment spanning exons 14 and 15, followed by hybridization to an exon 15-specific complementary DNA probe. Eighty human thyroid neoplasms were examined for loss of heterozygosity of the APC locus, using primers flanking a hypervariable dinucleotide (CA) repeat (CB26) immediately adjacent to the APC gene. Of 71% informative samples, 2 showed allelic loss: a follicular adenoma (FA) and a nodule from a multinodular goiter (MNG). The DNA of 83 benign and malignant thyroid neoplasms and 4 thyroid carcinoma cell lines was examined for mutations within a 1200-basepair stretch of exon 15 by single strand conformation polymorphism. Five sets of overlapping primers were used for PCR. The anaplastic thyroid carcinoma cell line (ARO) had 1 APC allele with an adenine insertion at codon 1556 (ACTA to AACTA), leading to a premature stop codon at 1558. An anaplastic carcinoma had a mutation of codon 1346 (TCA-CCA; Ser to Pro). In summary, the APC gene is expressed in normal and neoplastic human thyroid tissue and is a target for inactivating mutations in some thyroid tumors.