Endocrine UnitDepartment of Clinical Therapeutics, School of Medicine, Alexandra General Hospital, Athens University, Athens, GreeceImmunology DepartmentAlexandra General Hospital, Athens, GreeceHematology-Lymphomas Department and BMT UnitEvaggelismos General Hospital, Athens, GreeceDepartment of Endocrinology-Endocrine OncologyTheageneio Cancer Hospital, Thessaloniki, Greece1st Endocrine Section and Diabetes CenterAlexandra General Hospital, Athens, Greece
Endocrine UnitDepartment of Clinical Therapeutics, School of Medicine, Alexandra General Hospital, Athens University, Athens, GreeceImmunology DepartmentAlexandra General Hospital, Athens, GreeceHematology-Lymphomas Department and BMT UnitEvaggelismos General Hospital, Athens, GreeceDepartment of Endocrinology-Endocrine OncologyTheageneio Cancer Hospital, Thessaloniki, Greece1st Endocrine Section and Diabetes CenterAlexandra General Hospital, Athens, Greece.
Eur J Endocrinol. 2015 Apr;172(4):501-9. doi: 10.1530/EJE-14-0817. Epub 2015 Jan 26.
Mutations in the RET gene are responsible for hereditary medullary thyroid cancer (MTC) and may vary between ethnic groups. We report the spectrum of mutations detected in patients with MTC in a referral center in Greece.
Screening for RET mutations was performed in 313 subjects from 188 unrelated families: 51 patients had clinical suspicion for familial disease, 133 were apparently sporadic, four patients had only C cell hyperplasia, and 125 were family members. Exons 8, 10, 11, and 13-16 were screened.
A total of 58 individuals (30.85%) were RET mutations carriers, 120 (63.8%) were finally classified as sporadic, 13 apparently sporadic cases (9.8%) were identified with RET mutation: ten carried the exon 8 at codon 533 mutation (previously reported), two the exon 14 at codon 804 mutation, and one the exon 13 at codon 768 mutation. Six patients (3.19%) with clinical features of multiple endocrine neoplasia type 2A and negative for RET mutations were classified as 'unknown cause'. The mutations of hereditary cases were as follows: 21 cases (36.2%) in exon 8 codon 533, 19 (32.8%) in exon 11 codon 634, nine (15.5%) in exon 10, five (8.6%) in exon 16, three (5.2%) in exon 14 codon 804, and one in exon 13 codon 768 (1.7%).
The spectrum of RET mutations in Greece differs from that in other populations and the prevalence of familial cases is higher. The exon 8 (Gly533Cys) mutation was the most prevalent in familial cases unlike other series, followed by exon 11 (codon 634) mutations which are the most frequent elsewhere. The wide application of genetic screening in MTC reveals new molecular defects and helps to characterize the spectrum of mutations in each ethnic group.
RET 基因突变是遗传性甲状腺髓样癌（MTC）的致病原因，其在不同种族间存在差异。我们报告了在希腊一个转诊中心的 MTC 患者中检测到的突变谱。
对 188 个无血缘关系的家族中的 313 名个体进行 RET 基因突变筛查：51 名患者有家族性疾病的临床可疑性，133 名患者为明显的散发性病例，4 名患者仅为 C 细胞增生，125 名患者为家族成员。筛选了外显子 8、10、11 和 13-16。
共有 58 名（30.85%）个体为 RET 基因突变携带者，最终 120 名（63.8%）被归类为散发性病例，13 名（9.8%）疑似散发性病例被发现携带 RET 突变：10 名携带外显子 8 密码子 533 突变（之前报道过），2 名携带外显子 14 密码子 804 突变，1 名携带外显子 13 密码子 768 突变。6 名（3.19%）具有 2 型多发性内分泌肿瘤临床特征且 RET 基因突变阴性的患者被归类为“原因不明”。遗传性病例的突变如下：外显子 8 密码子 533 21 例（36.2%），外显子 11 密码子 634 19 例（32.8%），外显子 10 9 例（15.5%），外显子 16 5 例（8.6%），外显子 14 密码子 804 3 例（5.2%），外显子 13 密码子 768 1 例（1.7%）。
希腊的 RET 基因突变谱与其他人群不同，家族性病例的患病率较高。外显子 8（Gly533Cys）突变是家族性病例中最常见的突变，与其他系列不同，其次是外显子 11（密码子 634）突变，这是其他地方最常见的突变。MTC 的遗传筛查的广泛应用揭示了新的分子缺陷，并有助于描述每个种族的突变谱。
