Analysis of RET Gene Point Mutation in a Family with Familial Medullary Thyroid Carcinoma / 대한이비인후과학회지

ABSTRACT

BACKGROUND AND OBJECTIVES: Hereditary medullary thyroid carcinoma is presented as a part of MEN2A (65-75%) or MEN2B, but can also be inherited alone, which is called familial medullary thyroid carcinoma. The author sought to detect point mutations of the RET proto-oncogene using the molecular genetic method on the family line of the familial medullary thyroid carcinoma, which is identified by the family history of an index patient, and to investigate the presence of point mutation carriers among the family members. SUBJECTS AND METHOD: DNA was extracted from the peripheral blood leukocyte of 5 patients who were assumed to have sporadic medullary thyroid carcinoma and 1 patient who was an index of a family line assumed to contain hereditary medullary thyroid carcinoma according to the family history. The PCR amplification of exons, 10, 11, 13, 14, 15, 16 was then carried out, and we investigated point mutations of the RET proto-oncogene using a DNA sequence analyzer. After identifying point mutation of the familial medullary carcinoma with them, the same investigation was carried out with their family. RESULTS: We identified point mutation of TGC (Cys)->CGC (Arg) at codon 618 of the RET proto-oncogene exon 10, using the automatic DNA sequence analyzing method on the index patient and detected the same point mutation with 4 of the 9 family members. Among them, the index patient and her mother who had biochemical and clinical symptoms underwent a total thyroidectomy and neck dissection and are now being followed up ; operations are scheduled for two other members later on. CONCLUSION: With the genetic analysis of RET proto-oncogene, we expect to overcome the limitations of the calcitonin stimulation test and that more complete approach through early diagnosis would be possible by carrying out the screening test for point mutation in patients with the hereditary medullary thyroid carcinoma.