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Abstract：
To determine genealogical, clinical and pathological characteristics of a cohort with Cys618Arg mutation from an Israeli multicenter MTC study.
Retrospective database analysis examining RET mutations and comparing Cys618Arg and Cys634Arg/Thr/Tyr subgroups.
Genetic testing was performed in 131/275 MTC patients (47.6%). RET mutations were found in 50/131 (38.2%), including Cys618Arg (28/50 cases,56%), and Cys634Arg/Thr/Tyr (15/50,30%). Through genealogical study, 31 MTC patients were found descendants of one family of Jewish Moroccan descent, accounting for 27/28 patients with documented Cys618Arg mutation and 4 patients without available genetic testing. Familial Cys618Arg cases (n=31) and Cys634Arg/Thr/Tyr cases (n=15, from 6 families) were compared. Although surgical age was similar (25.7 vs 31.3 years, p=0.19), the Cys618Arg group had smaller tumors (8.9mm vs 18.5mm, p=0.004) and lower calcitonin levels (33.9 vs 84.5 X/ULN, p=0.03). Youngest ages at MTC diagnosis were 8 and 3 years in Cys618Arg and Cys634Arg/Thr/Tyr cohorts, respectively. Long-term outcome was similar between groups. The Cys618Arg cohort had lower rates of pheochromocytoma (6.5% vs 53.3%, p=0.001) and primary hyperparathyroidism (3.2% vs 33.3%, p=0.01).
This is the first description of RET mutation distribution in Israel. Of 131 tested MTC patients, Cys618Arg was the predominant mutation. To the best of our knowledge, this is the largest cohort of Cys618Arg mutation described. For Cys618Arg and Cys634Arg/Thr/Tyr cohorts, MTC was diagnosed earlier than expected, likely due to familial genetic screening, and MTC outcomes were similar between groups. International studies are necessary to further characterize the clinical features of Cys618 mutations due to their relative rarity.
Retrospective database analysis examining RET mutations and comparing Cys618Arg and Cys634Arg/Thr/Tyr subgroups.
Genetic testing was performed in 131/275 MTC patients (47.6%). RET mutations were found in 50/131 (38.2%), including Cys618Arg (28/50 cases,56%), and Cys634Arg/Thr/Tyr (15/50,30%). Through genealogical study, 31 MTC patients were found descendants of one family of Jewish Moroccan descent, accounting for 27/28 patients with documented Cys618Arg mutation and 4 patients without available genetic testing. Familial Cys618Arg cases (n=31) and Cys634Arg/Thr/Tyr cases (n=15, from 6 families) were compared. Although surgical age was similar (25.7 vs 31.3 years, p=0.19), the Cys618Arg group had smaller tumors (8.9mm vs 18.5mm, p=0.004) and lower calcitonin levels (33.9 vs 84.5 X/ULN, p=0.03). Youngest ages at MTC diagnosis were 8 and 3 years in Cys618Arg and Cys634Arg/Thr/Tyr cohorts, respectively. Long-term outcome was similar between groups. The Cys618Arg cohort had lower rates of pheochromocytoma (6.5% vs 53.3%, p=0.001) and primary hyperparathyroidism (3.2% vs 33.3%, p=0.01).
This is the first description of RET mutation distribution in Israel. Of 131 tested MTC patients, Cys618Arg was the predominant mutation. To the best of our knowledge, this is the largest cohort of Cys618Arg mutation described. For Cys618Arg and Cys634Arg/Thr/Tyr cohorts, MTC was diagnosed earlier than expected, likely due to familial genetic screening, and MTC outcomes were similar between groups. International studies are necessary to further characterize the clinical features of Cys618 mutations due to their relative rarity.
摘要：
■要确定家谱，来自以色列多中心MTC研究的Cys618Arg突变队列的临床和病理学特征。
■回顾性数据库分析检查RET突变并比较Cys618Arg和Cys634Arg/Thr/Tyr亚组。
■131/275例MTC患者（47.6%）进行了基因检测。在50/131（38.2％）中发现了RET突变，包括Cys618Arg（28/50例，56%），和Cys634Arg/Thr/Tyr（15/50,30%）。通过家谱研究，31名MTC患者被发现是一个犹太摩洛哥血统家庭的后裔，占27/28例记录有Cys618Arg突变的患者和4例未进行基因检测的患者。比较了家族性Cys618Arg病例（n=31）和Cys634Arg/Thr/Tyr病例（n=15，来自6个家庭）。尽管手术年龄相似（25.7岁vs31.3岁，p=0.19),Cys618Arg组肿瘤较小（8.9mmvs18.5mm，p=0.004）和较低的降钙素水平（33.9对84.5X/ULN，p=0.03)。在Cys618Arg和Cys634Arg/Thr/Tyr队列中，MTC诊断最年轻的年龄分别为8岁和3岁，分别。两组之间的长期结果相似。Cys618Arg组的嗜铬细胞瘤发生率较低(6.5%vs53.3%,p=0.001）和原发性甲状旁腺功能亢进（3.2%vs33.3%，p=0.01)。
■这是以色列对RET突变分布的首次描述。在131名接受测试的MTC患者中，Cys618Arg是主要突变。据我们所知,这是描述的最大的Cys618Arg突变队列。对于Cys618Arg和Cys634Arg/Thr/Tyr队列，MTC的诊断比预期的要早，可能是由于家族遗传筛查，两组间的MTC结局相似.由于Cys618突变的相对稀有性，国际研究有必要进一步表征Cys618突变的临床特征。
■回顾性数据库分析检查RET突变并比较Cys618Arg和Cys634Arg/Thr/Tyr亚组。
■131/275例MTC患者（47.6%）进行了基因检测。在50/131（38.2％）中发现了RET突变，包括Cys618Arg（28/50例，56%），和Cys634Arg/Thr/Tyr（15/50,30%）。通过家谱研究，31名MTC患者被发现是一个犹太摩洛哥血统家庭的后裔，占27/28例记录有Cys618Arg突变的患者和4例未进行基因检测的患者。比较了家族性Cys618Arg病例（n=31）和Cys634Arg/Thr/Tyr病例（n=15，来自6个家庭）。尽管手术年龄相似（25.7岁vs31.3岁，p=0.19),Cys618Arg组肿瘤较小（8.9mmvs18.5mm，p=0.004）和较低的降钙素水平（33.9对84.5X/ULN，p=0.03)。在Cys618Arg和Cys634Arg/Thr/Tyr队列中，MTC诊断最年轻的年龄分别为8岁和3岁，分别。两组之间的长期结果相似。Cys618Arg组的嗜铬细胞瘤发生率较低(6.5%vs53.3%,p=0.001）和原发性甲状旁腺功能亢进（3.2%vs33.3%，p=0.01)。
■这是以色列对RET突变分布的首次描述。在131名接受测试的MTC患者中，Cys618Arg是主要突变。据我们所知,这是描述的最大的Cys618Arg突变队列。对于Cys618Arg和Cys634Arg/Thr/Tyr队列，MTC的诊断比预期的要早，可能是由于家族遗传筛查，两组间的MTC结局相似.由于Cys618突变的相对稀有性，国际研究有必要进一步表征Cys618突变的临床特征。
