Mutations of the adenomatous polyposis coli gene in sporadic thyroid neoplasms.
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.
Division of Endocrinology, Cedars-Sinai Medical Center, University of California School of Medicine, Los Angeles 90048.
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K
Zeki
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Spambalg
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N
Sharifi
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R
Gonsky
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JA
Fagin
D000236:Adenoma / Q000737:chemistry / Q000209:etiology / Q000235:genetics*; D001483:Base Sequence; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D017491:Genes, APC; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D013961:Thyroid Gland / Q000502:physiology; D013964:Thyroid Neoplasms / Q000737:chemistry / Q000209:etiology / Q000235:genetics*
D004273:DNA, Neoplasm; D012333:RNA, Messenger