RET oncogene mutations in medullary thyroid carcinoma in Mexican families.
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.
González
Beatriz
B
Unidad de Investigación Médica en Enfermedades Oncológicas, Instituto Mexicano del Seguro Social (IMSS), Mexico City, Mexico.
Salcedo
Mauricio
M
Medrano
María Elena
ME
Mantilla
Alejandra
A
Quiñónez
Guadalupe
G
Benítez-Bribiesca
Luis
L
Rodríguez-Cuevas
Sergio
S
Cabrera
Lourdes
L
de León
Beatriz
B
Altamirano
Nelly
N
Tapia
José
J
Dawson
Brian
B
D000293:Adolescent; D000328:Adult; D018276:Carcinoma, Medullary / Q000235:genetics* / Q000473:pathology; D002648:Child; D005260:Female; D006801:Humans; D008297:Male; D008800:Mexico; D008875:Middle Aged; D018813:Multiple Endocrine Neoplasia Type 2a / Q000235:genetics* / Q000473:pathology; D018814:Multiple Endocrine Neoplasia Type 2b / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology
D011518:Proto-Oncogene Proteins; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases