Related Experiment Videos
A frequent mutation/polymorphism in tumor suppressor gene INK4B (MTS-2) in papillary and medullary thyroid cancer
P E Goretzki1, V Gorelov, C Dotzenrath
1Klinik fuer Allgemein- und Unfallchirurgie, Heinrich Heine Universitaet Düsseldorf, Germany.
Background:
Structural genetic changes of tumor suppressor genes MTS-1/INK4A and MTS-2/INK4B were demonstrated in a variety of human cancers but not in thyroid cancer until now.
Methods:
Because MTS-2 encodes the tumor suppressor p15, a protein related to the transforming growth factor-beta inhibition of many epithelial cells such as thyrocytes, we investigated MTS-1 and MTS-2 genes in 87 thyroid cancers (29 papillary, 26 follicular, 31 medullary, and 1 anaplastic), 8 goiters, and 38 control DNAs by using a semiquantitative polymerase chain reaction technique.
Results:
We failed to demonstrate homozygous deletions of MTS-1 and MTS-2 in thyroid tumors, but we demonstrated a highly frequent base pair exchange of the MTS-2 gene 27 codons upstream the 5' end of exon 2. This genetic change formerly described as polymorphism was found to a lesser degree (15%), in control DNA when compared with papillary thyroid cancer and medullary thyroid cancer (35% and 32%, respectively), and it paralleled a higher prevalence of extensive lymph node metastases in thyroid cancer (p < 0.01). In addition, we could demonstrate that genetic changes at site 27 upstream the 5' end of exon 2 were harbored as somatic mutations in 2 of 10 thyroid cancers with simultaneously investigated corresponding control tissue.
Conclusions:
We conclude that base pair exchange at this site most likely has biologic importance for the tumor suppressor p15 and may contribute to tumorigenesis and lymphatic spread of differentiated and medullary thyroid cancer.
Insights
Genetic changes in the MTS-2 gene, specifically a base pair exchange, were identified in thyroid cancers. This alteration in the tumor suppressor p15 may contribute to thyroid cancer development and spread.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Tumor suppressor genes MTS-1/INK4A and MTS-2/INK4B are crucial in various human cancers.
- Previous research had not identified structural genetic changes in these genes within thyroid cancer.
Purpose of the Study:
- To investigate the role of MTS-1 and MTS-2 genes in thyroid tumorigenesis.
- To determine if genetic alterations in MTS-2 are associated with thyroid cancer development and progression.
Main Methods:
- Analysis of MTS-1 and MTS-2 genes in 87 thyroid cancers, 8 goiters, and 38 control DNAs.
- Utilized semiquantitative polymerase chain reaction (PCR) technique.
- Investigated genetic changes 27 codons upstream the 5' end of exon 2 in MTS-2.
Main Results:
- No homozygous deletions of MTS-1 and MTS-2 were found in thyroid tumors.
- A frequent base pair exchange in the MTS-2 gene was observed, occurring more often in papillary (35%) and medullary (32%) thyroid cancers than in controls (15%).
- This genetic alteration correlated with a higher prevalence of lymph node metastases in thyroid cancer (p < 0.01) and was identified as a somatic mutation in some cases.
Conclusions:
- The base pair exchange in MTS-2 likely impacts the tumor suppressor p15's function.
- This genetic alteration may play a role in the tumorigenesis and lymphatic spread of differentiated and medullary thyroid cancers.