The Occurrence and the Type of Germline Mutations in theRETGene in Patients with Medullary Thyroid Carcinoma and Their Unaffected Kindred's from Central Poland

Abstract

We aimed to investigate the occurrence and types of pathogenic mutations in the RET gene in patients with MTC of the Central Poland population and in their relatives. DNA was extracted from the peripheral blood lymphocytes of a total of 330 persons, including 235 MTC patients and 95 of their unaffected kindred's. Exons 10, 11, 13, 14, 15 and 16 of the RET gene were amplified by PCR and sequenced. Sixty-seven people were found to carry pathogenic, germline mutations in the RET gene. In exon 10, C609F, C609R and C609Y (3 families), C618G, C618F (2 families), and C620G (4 families) mutations were identified. In exon 11, C634R (8 families) and C649L mutations (1 patient) were found. Five families carried Y791F mutation in exon 13. One patient with PTC revealed the presence of a Y791F mutation. In 3 families, exon 14 of the RET gene harbored the following mutations: V804L (1 patient), E819K (1 patient) and R844Q (1 patient). In 1 family, the S891A mutation was identified in exon 15, 3 families were found to carry mutations in exon16, R912P in 1 family and M918T in 2 families. In summary, of the 235 patients affected by MTC, 46 (19.6%) carried pathogenic RET gene mutations, 1 patient with RET mutation had kidney carcinoma, and 1 had PTC. The results show the occurrence of a variety of mutations prevalent in patients with MTC in the population of Central Poland. These results may contribute to a better diagnosis of medullary thyroid carcinoma.

The Frequency of Selected Polymorphic Variants of the RET Gene in Patients with Medullary Thyroid Carcinoma and in the General Population of Central Poland

“…As the most recent data (6,24) suggested, mutation F791Y may be much more frequent than it had previously been thought to occur.…”

“…The product of the sequencing reaction was subjected to electrophoresis on 5% denaturing polyacrylamide gel in a Perkin Elmer ABI Prism 377 DNA sequencer. Detailed information can be found in publication Paszko et al 2007 (6).…”

“…In our earlier article we presented a spectrum of the RET gene mutations prevalent in the population of Central Poland (6). It represents the majority of mutations of this gene reported in the world literature (7,8,9).…”

Diagnostic and surgical dilemmas in hereditary medullary thyroid carcinoma

“…Consistency in the virulence of specific RET mutations has led some clinicians to tailor the timing of prophylactic surgery in disease carriers based upon genetic risk stratification of disease onset and progression (Table II). 6, 7, 39, 40 The RET mutations may be divided according to three classifications based upon the level of risk they entail.…”

Screening of RET gene mutations in Chinese patients with medullary thyroid carcinoma and their relatives

“…Approximately 25 % of MTC represents inherited disease, while the rest is as a sporadic tumor [1][2][3][4]. MTC originates from the parafollicular cells (C cells) and produces the hormone calcitonin.…”