Allelotype of human thyroid tumors: loss of chromosome 11q13 sequences in follicular neoplasms.
Two classes of genes are the targets of mutations involved in human tumorigenesis: oncogenes, the activation of which leads to growth stimulation, and tumor suppressor genes, which become tumorigenic through loss of function, often through allelic deletion. To obtain evidence for a role for tumor suppressor genes in thyroid tumorigenesis, we examined DNA from 80 thyroid neoplasms for loss of heterozygosity in multiple chromosomal loci using 19 polymorphic genomic probes. None of the informative thyroid tumors studied had allelic loss detected with probes for chromosome 2q (D2S44), 3p (D3F15S2, D3S32), 3q (D3S46), 4p (D4S125), 6p (D6S40), 8q (D8S39), 9q (D9S7), 12p (D12S14), 13q (D13S52), 17p (D17S30), or 18q (D18S10). One of eight of the follicular adenomas had a 10q deletion detected with marker D10S15, and one of 26 had a 10q deletion detected with D10S25. One of two of the follicular carcinomas had an 11p deletion in the H-ras locus. The most significant findings were on chromosome 11q13, the site containing the putative gene predisposing to multiple endocrine neoplasia type I. Four of 27 follicular adenomas had loss of heterozygosity for probes in this region. Allelic deletions were detected with the following probes: D11S149, PYGM, D11S146, and INT2. None of 13 informative papillary carcinomas and none of two follicular carcinomas had loss of heterozygosity detectable with these 11q13 markers. Allelic loss is a relatively infrequent event in human thyroid tumors. Deletions of chromosome 11q13 are present in about 14% of follicular, but not papillary, neoplasms.(ABSTRACT TRUNCATED AT 250 WORDS)
Matsuo
K
K
Department of Medicine, Cedars-Sinai Medical Center, University of California School of Medicine, Los Angeles 90048.
Tang
S H
SH
Fagin
J A
JA
D000483:Alleles; D001483:Base Sequence; D015139:Blotting, Southern; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D015342:DNA Probes; D004273:DNA, Neoplasm / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel; D016147:Genes, Tumor Suppressor / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D009857:Oncogenes / Q000235:genetics; D010641:Phenotype; D011110:Polymorphism, Genetic; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology
D015342:DNA Probes; D004273:DNA, Neoplasm