Rare loss of heterozygosity of the MTS1 and MTS2 tumor suppressor genes in differentiated human thyroid cancer.
Loss of heterozygosity (LOH) of the MTS1 (p16) tumor suppressor gene has been reported to occur frequently in thyroid cancer cell lines. In order to determine the frequency of LOH for these multiple tumor suppressor genes, we used microsatellite markers IFNA and D9S171 to perform differential quantitative polymerase chain reaction. Tumor DNA was isolated from native sections of tumor tissue. Control DNA was isolated from blood. PCR products were separated on 6% polyacrylamide sequencing gels and quantified according to peak height and area. Analysis was informative in 70% of cases for both markers, and in 88% for at least one out of both. LOH was found in 3 out of 35 informative patients (8.6%) with papillary thyroid cancer, in 1 out of 7 patients with follicular thyroid cancer (14.2%), and in 0 out of 18 medullary cancers (0%). No LOH was found in 11 informative patients with multinodular goitre, 7 with follicular adenoma, 4 with Graves' disease, and 6 with other thyroid disease. 75% of LOH was found in T1 and T2 stages, it was not more frequent in patients with lymphonodular metastasis. The low frequency of LOH in these types of thyroid cancer argues against a role of loss of heterozygosity at the MTS 1 and 2 gene locus in the development of differentiated thyroid neoplasia.
Schulte
K M
KM
Dept. of General and Trauma Surgery, Heinrich Heine University, Düsseldorf, Germany.
Staudt
S
S
Niederacher
D
D
Finken-Eigen
M
M
Köhrer
K
K
Goretzki
P E
PE
Röher
H D
HD
D000236:Adenoma / Q000235:genetics* / Q000378:metabolism; D000483:Alleles; D018265:Carcinoma, Papillary, Follicular / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics*; D018797:Cell Cycle Proteins; D002454:Cell Differentiation / Q000235:genetics; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D004273:DNA, Neoplasm / Q000032:analysis; D004276:DNA, Satellite / Q000032:analysis; D004791:Enzyme Inhibitors / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D006579:Heterozygote; D006801:Humans; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism; D025521:Tumor Suppressor Proteins
C493966:CDKN2B protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004273:DNA, Neoplasm; D004276:DNA, Satellite; D004791:Enzyme Inhibitors; D025521:Tumor Suppressor Proteins