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Frequent RET rearrangements in thyroid papillary microcarcinoma detected by interphase fluorescence in situ
R Corvi1, M Martinez-Alfaro, H R Harach
1European Center for the Validation of Alternative Methods (RC), Institute for Health and Consumer Protection, Ispra, Italy. corvi@iarc.fr
Abstract:
Papillary thyroid microcarcinomas (measuring 1 cm or less in diameter) are very common thyroid tumors, which are present in 10% to 35% of post-mortem histopathological examinations of individuals whose death was due to a cause other than thyroid cancer. The molecular basis of this tumor is still poorly understood. Somatic mutations are better characterized in clinically evident papillary thyroid carcinomas (PTCs), the most common involving the proto-oncogene RET, which maps to 10q11.2. Molecular alterations of RET always lead to intra- or interchromosomal rearrangements. In this study we have investigated the status of RET in 21 microcarcinomas, by means of interphase fluorescence in situ hybridization (FISH). RET was rearranged in 52% of microcarcinomas, a statistically significant higher frequency than that found previously in clinically evident PTCs using the same technique. Moreover, interphase FISH allowed us to detect a putative novel type of rearrangement in a microcarcinoma, and we observed trisomies of chromosome 10 and other chromosomes in two adenomas surrounding two of the microcarcinomas. The strikingly high frequency of RET rearrangements in microcarcinomas strongly suggests that RET plays a role in the initiation of thyroid tumorigenesis but does not seem to be necessary for the further progression of the tumor.
Insights
Papillary thyroid microcarcinomas, common tumors, show frequent RET gene rearrangements. This suggests RET is crucial for initiating thyroid cancer but not its progression.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Papillary thyroid microcarcinomas are common, yet their molecular basis is poorly understood.
- Clinically evident papillary thyroid carcinomas (PTCs) often involve the RET proto-oncogene.
- RET alterations typically result in chromosomal rearrangements.
Purpose of the Study:
- To investigate the status of RET gene rearrangements in papillary thyroid microcarcinomas.
- To compare the frequency of RET rearrangements in microcarcinomas versus clinically evident PTCs.
Main Methods:
- Interphase fluorescence in situ hybridization (FISH) was used to analyze RET gene status.
- The study examined 21 cases of papillary thyroid microcarcinomas.
Main Results:
- RET rearrangements were detected in 52% of the analyzed microcarcinomas.
- This frequency is significantly higher than previously reported for clinically evident PTCs using FISH.
- A novel type of RET rearrangement was observed, along with chromosome 10 trisomies in surrounding adenomas.
Conclusions:
- The high frequency of RET rearrangements suggests a significant role in thyroid tumorigenesis initiation.
- RET alterations may not be essential for the further progression of papillary thyroid microcarcinomas.