González Beatriz, Salcedo Mauricio, Medrano María Elena, Mantilla Alejandra, Quiñónez Guadalupe, Benítez-Bribiesca Luis, Rodríguez-Cuevas Sergio, Cabrera Lourdes, de León Beatriz, Altamirano Nelly, Tapia José, Dawson Brian
Unidad de Investigación Médica en Enfermedades Oncológicas, Instituto Mexicano del Seguro Social (IMSS), Mexico City, Mexico.
Arch Med Res. 2003 Jan-Feb;34(1):41-9. doi: 10.1016/s0188-4409(02)00461-7.
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.
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.
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.
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.
在三种不同综合征的背景下，已发现不同的RET原癌基因突变与遗传性甲状腺髓样癌（MTC）相关，这三种综合征包括2A型多发性内分泌腺瘤病（MEN 2A）、2B型多发性内分泌腺瘤病（MEN 2B）和家族性甲状腺髓样癌（FMTC）。这些突变已在不同人群中记录，但迄今为止，墨西哥家族中尚无相应研究。我们的目的是鉴定患有遗传性或散发性MTC（SMTC）的墨西哥家族中的RET突变，并寻找RET蛋白表达作为MTC肿瘤的预后标志物。
研究了9个患有MTC的无关家族，其中2个为MEN 2A家族，3个为MEN 2B家族，4个为SMTC家族。分析了循环淋巴细胞和肿瘤样本DNA中RET原癌基因第10、11和13 - 16外显子的筛查情况。对相应肿瘤进行RET免疫染色。
在3名无关的MEN 2B个体中存在胚系918 ATG→ACG RET突变，1名SMTC个体中存在相应的体细胞突变；在一个MEN 2A家族的2名相关患者中检测到634 TGC→TTC RET突变，在第二个MEN 2A家族的12名相关个体中检测到634 TGC→TAC RET突变。在所有MTC肿瘤中均检测到RET蛋白表达，染色强度不同。
在墨西哥MTC患者中发现的RET突变与全球多个MTC家族先前报道的突变相似。这表明RET突变高度保守，且MTC的病因在很大程度上不依赖于环境因素或种族差异。在MTC组织切片中检测RET蛋白作为预后标志物并无用处。
