Tumor suppressor genes in human thyroid neoplasms: p53 mutations are associated undifferentiated thyroid cancers

1995 ◽  
Vol 18 (2) ◽  
pp. 140-142 ◽  
Author(s):  
James A. Fagin
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressor Genes ◽  
Thyroid Neoplasms ◽  
Human Thyroid ◽  
P53 Mutations ◽  
Suppressor Genes ◽  
Thyroid Cancers

scholarly journals Frequent Loss of Heterozygosity on Chromosomes 3p and 17p without VHL or p53 Mutations Suggests Involvement of Unidentified Tumor Suppressor Genes in Follicular Thyroid Carcinoma1

1997 ◽  
Vol 82 (11) ◽  
pp. 3684-3691
Author(s):  
Stefan K. G. Grebe ◽  
Bryan McIver ◽  
Ian D. Hay ◽  
Patricia S.-C. Wu ◽  
Lea M. Z. Maciel ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Thyroid Carcinoma ◽  
Loss Of Heterozygosity ◽  
Tumor Suppressor Genes ◽  
Average Rate ◽  
Gene Mutations ◽  
Follicular Adenoma ◽  
Papillary Thyroid ◽  
P53 Mutations ◽  
Suppressor Genes

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.

scholarly journals Structural and functional analysis of oncogenes and tumor suppressor genes in adult T-cell leukemia/lymphoma shows frequent p53 mutations

Blood ◽  
1992 ◽  
Vol 80 (12) ◽  
pp. 3205-3216 ◽  
Author(s):  
E Cesarman ◽  
A Chadburn ◽  
G Inghirami ◽  
G Gaidano ◽  
DM Knowles
Keyword(s):  
T Cell ◽  
Tumor Suppressor ◽  
Tumor Suppressor Genes ◽  
Type I ◽  
T Cell Leukemia ◽  
P53 Mutations ◽  
Cell Leukemia ◽  
Suppressor Genes ◽  
Adult T Cell Leukemia ◽  
Myc Gene

Abstract The human T-cell lymphotropic virus type I (HTLV-I) is capable of inducing adult T-cell leukemia/lymphoma (ATLL). However, the long latency period between infection and development of ATLL, as well as the small fraction of the infected population that actually develops this disease, suggest that additional factors are involved in its pathogenesis. Therefore, we performed a molecular analysis of 10 cases of ATLL presenting in a nonendemic area that were shown to have HTLV-I sequences by polymerase chain reaction as well as clonal T-cell receptor beta gene rearrangements. We analyzed these cases for alterations in some of the oncogenes and tumor suppressor genes frequently involved in hematopoietic neoplasia. Specifically, we used a single-strand conformation polymorphism assay to determine the presence of mutations in the p53 tumor suppressor gene, as well as the K-RAS, N-RAS, H-RAS, and c-myc oncogenes. In addition, we studied the c-myc gene for rearrangements by Southern blotting and assessed expression of the retinoblastoma (Rb) and p53 genes by immunostaining. Analysis of the c-myc gene and the RAS family of oncogenes did not show any alterations. Also, the Rb gene was expressed in all cases analyzed. However, we found mutations of the p53 gene in 3 of the 10 cases and these results were confirmed by sequence analysis. In two of these cases, we showed by restriction fragment length polymorphism analysis of chromosome 17p sequences that the p53 mutations were accompanied by a loss of heterozygocity. Also, these mutations correlated with an altered pattern of p53 expression. Thus, mutations in the p53 locus may be a cofactor for the development of ATLL in some cases, whereas the c-myc, Rb, and RAS genes do not appear to be involved in these neoplasms.

scholarly journals Structural and functional analysis of oncogenes and tumor suppressor genes in adult T-cell leukemia/lymphoma shows frequent p53 mutations

Blood ◽  
1992 ◽  
Vol 80 (12) ◽  
pp. 3205-3216 ◽  
Author(s):  
E Cesarman ◽  
A Chadburn ◽  
G Inghirami ◽  
G Gaidano ◽  
DM Knowles
Keyword(s):  
T Cell ◽  
Tumor Suppressor ◽  
Tumor Suppressor Genes ◽  
Type I ◽  
T Cell Leukemia ◽  
P53 Mutations ◽  
Cell Leukemia ◽  
Suppressor Genes ◽  
Adult T Cell Leukemia ◽  
Myc Gene

The human T-cell lymphotropic virus type I (HTLV-I) is capable of inducing adult T-cell leukemia/lymphoma (ATLL). However, the long latency period between infection and development of ATLL, as well as the small fraction of the infected population that actually develops this disease, suggest that additional factors are involved in its pathogenesis. Therefore, we performed a molecular analysis of 10 cases of ATLL presenting in a nonendemic area that were shown to have HTLV-I sequences by polymerase chain reaction as well as clonal T-cell receptor beta gene rearrangements. We analyzed these cases for alterations in some of the oncogenes and tumor suppressor genes frequently involved in hematopoietic neoplasia. Specifically, we used a single-strand conformation polymorphism assay to determine the presence of mutations in the p53 tumor suppressor gene, as well as the K-RAS, N-RAS, H-RAS, and c-myc oncogenes. In addition, we studied the c-myc gene for rearrangements by Southern blotting and assessed expression of the retinoblastoma (Rb) and p53 genes by immunostaining. Analysis of the c-myc gene and the RAS family of oncogenes did not show any alterations. Also, the Rb gene was expressed in all cases analyzed. However, we found mutations of the p53 gene in 3 of the 10 cases and these results were confirmed by sequence analysis. In two of these cases, we showed by restriction fragment length polymorphism analysis of chromosome 17p sequences that the p53 mutations were accompanied by a loss of heterozygocity. Also, these mutations correlated with an altered pattern of p53 expression. Thus, mutations in the p53 locus may be a cofactor for the development of ATLL in some cases, whereas the c-myc, Rb, and RAS genes do not appear to be involved in these neoplasms.

Rare Loss of Heterozygosity of the MTS1 and MTS2 Tumor Suppressor Genes in Differentiated Human Thyroid Cancer

1998 ◽  
Vol 30 (09) ◽  
pp. 549-554 ◽  
Author(s):  
K. Schulte ◽  
S. Staudt ◽  
D. Niederacher ◽  
M. Finken-Eigen ◽  
K. Köhrer ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Tumor Suppressor ◽  
Loss Of Heterozygosity ◽  
Tumor Suppressor Genes ◽  
Human Thyroid ◽  
Suppressor Genes
Sign in / Sign up

Export Citation Format

Share Document