Frequent loss of heterozygosity on chromosomes 3p and 17p without VHL or p53 mutations suggests involvement of unidentified tumor suppressor genes in follicular thyroid carcinoma.
Follicular thyroid carcinoma (FTC) exhibits frequent loss of heterozygosity (LOH) on chromosomes 10q and 3p, suggesting involvement of tumor suppressor genes. We screened 14 FTC (10 Hurthle cell carcinomas and 4 nonoxyphilic FTC), 14 papillary thyroid carcinomas, and 7 follicular adenomas for LOH on chromosome arms 1p, 3p, 3q, 10p, 10q, 11p, 11q, 13q, 17p, and 17q. LOH was more frequent in FTC than in follicular adenoma or papillary thyroid carcinoma. In FTC, rates of LOH on 3p (86%), 17p (72%), and 10q (57%) were higher than the average rate of LOH (33%; P < 0.05). Most frequently involved were 3p21-25 and 17p13.1-13.3, the sites for the VHL (3p25-26) and p53 (17p13.1) tumor suppressors. We, therefore, characterized these genes by dideoxy fingerprinting and DNA sequencing. Two FTC had mutations in p53, but only 1 of these exhibited LOH at 17p. No VHL gene mutations were found. Thus, neither p53 nor VHL genes play a significant role in the pathogenesis of differentiated thyroid cancer. LOH on 17p, but not on 3p or 10q, was correlated with mortality. Accordingly, 3p and 10q LOH may represent early, and 17p LOH late, events in FTC development. The data suggest the presence of novel tumor suppressor genes on chromosomes 3p and 17p that may be important in the pathogenesis of FTC.
Grebe
S K
SK
Department of Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA.
McIver
B
B
Hay
I D
ID
Wu
P S
PS
Maciel
L M
LM
Drabkin
H A
HA
Goellner
J R
JR
Grant
C S
CS
Jenkins
R B
RB
Eberhardt
N L
NL
D018263:Adenocarcinoma, Follicular / Q000235:genetics* / Q000401:mortality; D000293:Adolescent; D000328:Adult; D000368:Aged; D002886:Chromosomes, Human, Pair 17; D002893:Chromosomes, Human, Pair 3; D016172:DNA Fingerprinting; D004252:DNA Mutational Analysis; D005260:Female; D016147:Genes, Tumor Suppressor; D016158:Genes, p53 / Q000235:genetics; D006801:Humans; D008025:Ligases; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D011506:Proteins / Q000235:genetics; D017422:Sequence Analysis, DNA; D015996:Survival Rate; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000401:mortality; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein
D011506:Proteins; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D008025:Ligases; C497446:VHL protein, human