RET原癌基因点突变所致多发性内分泌腺瘤病2B型一例家系研究

A case report and pedigree study of a single point mutation in RET proto-oncogene and type 2B multiple endocrine neoplasia

目的 研究 1例中国家系中RET原癌基因点突变与多发性内分泌腺瘤病 2B型 (MEN 2B)发病的相互关系及其遗传特征。方法 收集 1例MEN 2B患者术后甲状腺髓样癌肿瘤组织和外周血DNA标本及其父母外周血DNA标本运用PCR和逆转录PCR技术以及直接基因测序技术对上述标本中RET原癌基因 16号外显子区域进行分子检测。结果 在患者肿瘤组织 (c)DNA及其外周血DNA中均检测到RET原癌基因 16号外显子 918密码子处基因点突变 ,即 :918Met(ATG)→Thr(ACG)。且由基因测序图示 ,该突变为杂合子错义突变。而患者父母外周血DNA样本中均未发现上述RET原癌基因点突变。结论 与国外报道相似 ,在中国MEN 2B患者中 ,也找到了RET原癌基因 16号外显子基因点突变 918Met(ATG)→Thr(ACG)。虽然其发病具有遗传倾向 ,但同样存在散发病例。MEN

Objective To determine the relationship between a single point mutation in RET proto oncogene and the occurrence of multiple endocrine neoplasia type 2B(MEN 2B) in a Chinese pedigree. Methods We used the methods of polymerase chain reaction (PCR), reverse transcriptase polymerase chain reaction (RT PCR) and direct gene sequencing of PCR products by an automated DNA sequencer to scan the entire exon 16 of RET proto oncogene in the tumor (c)DNA from one patient with MEN 2B and the leukocyte DNA from this patient and both of his parents. Results We found the same mutation Met(ATG) →Thr(ACG) at codon 918 in exon 16 of RET proto oncogene in both the tumor (c)DNA and leukocyte DNA of the MEN 2B patient in the form of homozygous missense mutation, but there was no corresponding mutation in leukocytes DNA of his parents.Conclusion We propose that in Chinese population, the point mutation M918T is also associated with the onset of MEN 2B and this case of MEN 2B is sporadic. Thus it may provide a genetic basis for the early diagnosis and treatment of patients suffering from MEN 2B and their at risk family members in Chinese population.