Related Experiment Videos
Genetic analysis of a papillary thyroid carcinoma in a patient with MEN1
D Desai1, L A McPherson, J P Higgins
1The Department of Surgery, Stanford University School of Medicine, California 94305-5494, USA.
Background:
MENI is an inherited tumor syndrome characterized by the development of tumors of the parathyroid, the anterior pituitary and the pancreatic islets. Tumors of these endocrine glands in MEN1 patients demonstrate loss of heterozygosity (LOH) at the locus of the MEN1 tumor suppressor gene. Menin, the protein encoded by the MEN1 gene, is ubiquitously expressed in endocrine tissue, and less commonly these patients can present with tumors of other endocrine tissues, including thyroid and adrenal. We hypothesize that MEN1 gene mutation may be involved in the oncogenesis of other less common tumors.
Methods:
We report a MEN1 patient who was found to have metastatic papillary thyroid cancer at the time of neck exploration for hyperparathyroidism. Genetic analysis of tumor tissue was performed using one intragenic (D11S4946) and two flanking (D11S4945 and D11S4940) polymorphic markers.
Results:
Two of the markers were informative. Consistent with previous studies, there was LOH in the parathyroid adenoma identified with the intragenic marker D11S4946. However, the papillary cancer was found to be heterozygous at two informative markers.
Conclusions:
The lack of obvious LOH of the MEN1 locus in the papillary cancer suggests that, in contrast to parathyroid adenoma, deletion of the MEN1 tumor suppressor gene is not etiologically related to the oncogenesis of the papillary cancer in this patient.
Insights
Multiple Endocrine Neoplasia type 1 (MEN1) is linked to parathyroid tumors, but not papillary thyroid cancer. Genetic analysis showed loss of heterozygosity in parathyroid adenoma, but not in papillary cancer, suggesting different oncogenesis mechanisms.
Area of Science:
- Endocrinology
- Oncology
- Genetics
Background:
- Multiple Endocrine Neoplasia type 1 (MEN1) is an inherited syndrome causing tumors in parathyroid, pituitary, and pancreatic glands.
- MEN1-associated tumors typically exhibit loss of heterozygosity (LOH) at the MEN1 tumor suppressor gene locus.
- While common in MEN1, other endocrine tumors like thyroid and adrenal are less frequent.
Observation:
- A MEN1 patient presented with metastatic papillary thyroid cancer during surgery for hyperparathyroidism.
- Genetic analysis of tumor tissues was conducted using polymorphic markers near the MEN1 gene locus.
Findings:
- Loss of heterozygosity (LOH) at the MEN1 locus was confirmed in the parathyroid adenoma.
- The papillary thyroid cancer, however, remained heterozygous at the informative markers, indicating no LOH.
Implications:
- The absence of LOH in papillary thyroid cancer suggests that MEN1 gene deletion is not the primary driver of its oncogenesis.
- This finding contrasts with the established role of MEN1 gene inactivation in parathyroid tumor development.
- Further research is needed to elucidate the specific genetic pathways involved in MEN1-related papillary thyroid cancer.