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RET oncogene mutations in medullary thyroid carcinoma in Mexican families
Beatriz González1, Mauricio Salcedo, María Elena Medrano
1Unidad de Investigación Médica en Enfermedades Oncológicas, Instituto Mexicano del Seguro Social (IMSS), Mexico City, Mexico.
Background:
Different RET oncogene mutations have been found to be associated with inherited medullary thyroid carcinoma (MTC) in the context of three different syndromes including multiple endocrine neoplasia types 2A (MEN 2A) and 2B (MEN 2B) and familial medullary thyroid carcinoma (FMTC). These mutations have been recorded in different populations, but to date there is no corresponding study in Mexican families. Our purpose was identification of RET mutations in Mexican families with inherited or sporadic MTC (SMTC) and search for RET protein expression as prognostic marker in MTC tumors.
Methods:
Nine unrelated families with MTC corresponding either to two MEN 2A, three MEN 2B, or four SMTC were studied. Screening of exons 10, 11, and 13-16 of RET oncogene in DNA from circulating lymphocytes and tumor samples were analyzed. Immuno- staining for RET was performed in the corresponding tumor.
Results:
Germline 918 ATG-->ACG RET mutation was present in three unrelated MEN 2B individuals and corresponding somatic mutation in one individual with SMTC; 634 TGC-->TTC RET mutation was detected in two related patients in an MEN 2A family and the 634 TGC-->TAC RET mutation was detected in 12 related individuals from a second MEN 2A family. RET protein expression was detected in all MTC tumors showing different staining intensity.
Conclusions:
RET mutations found in Mexican patients with MTC are similar to those previously reported in several MTC families worldwide. This indicates that RET mutations are highly conserved and that MTC etiology does not depend to a great extent on environmental factors or ethnic differences. Detection of RET protein in MTC tissue sections is not useful as prognostic marker.
Insights
RET mutations in Mexican families with medullary thyroid carcinoma (MTC) are similar to those found globally, indicating conserved MTC etiology. RET protein expression is not a reliable prognostic marker for MTC tumors.
Area of Science:
- Genetics
- Oncology
- Endocrinology
Background:
- Medullary thyroid carcinoma (MTC) is linked to RET oncogene mutations, forming part of inherited syndromes like MEN 2A, MEN 2B, and FMTC.
- Previous studies documented RET mutations across diverse populations, but none focused on Mexican families.
- The study aimed to identify RET mutations in Mexican MTC families and assess RET protein expression as a prognostic indicator.
Purpose of the Study:
- Identify RET oncogene mutations in Mexican families with inherited or sporadic MTC.
- Investigate the presence and utility of RET protein expression as a prognostic marker in MTC tumors.
Main Methods:
- Analyzed DNA from nine unrelated families (2 MEN 2A, 3 MEN 2B, 4 SMTC) for RET mutations in specific exons.
- Utilized peripheral blood lymphocytes and tumor tissue for genetic screening.
- Performed immunohistochemical staining for RET protein on MTC tumor samples.
Main Results:
- Identified specific RET mutations (918 ATG-->ACG and 634 TGC-->TTC/TAC) in MEN 2A, MEN 2B, and sporadic MTC cases within the studied Mexican families.
- Detected RET protein expression in all analyzed MTC tumors, with varying staining intensities.
- Found no correlation between RET protein expression levels and MTC prognosis.
Conclusions:
- The spectrum of RET mutations in Mexican MTC patients mirrors global findings, suggesting conserved MTC pathogenesis irrespective of ethnicity or environment.
- RET protein expression in MTC tissue is not a useful prognostic biomarker.
- This study highlights the importance of genetic screening for RET mutations in MTC.