Germline CDKN1B/p27Kip1 mutation in multiple endocrine neoplasia
Germline CDKN1B/p27Kip1 mutation in multiple endocrine neoplasia
复制标题
DOI：
10.1210/jc.2006-2843
复制
发表时间：
2007-08-01
影响因子：
5.8
通讯作者：
Aaltonen, Lauri A.
中科院分区：
文献类型：
--
作者：
Georgitsi, Marianthi;Raitila, Anniina;Aaltonen, Lauri A.
内容：MEN 1基因的种系突变易导致多发性内分泌瘤样病变1型（MEN 1）综合征，但在临床MEN 1病例中，高达20-25%的病例中未发现MEN 1突变。最近，在一个疑似MEN 1家系中发现了编码p27（Kip 1）的CDKN 1B基因的种系突变，该家系有两名肢端肥大症患者。目的：我们的目的是评估CDKN 1B/p27（Kip 1）在临床怀疑MEN 1但MEN 1生殖系突变检测阴性的患者以及家族性和散发性肢端肥大症/垂体腺瘤患者中的人类肿瘤易感性中的作用。设计：通过PCR扩增和直接测序分析基因组DNA中CDKN 1B/p27（Kip 1）基因的种系突变。设定：患者：36名荷兰人和1名德国人疑似MEN 1患者，他们先前对生殖系MEN 1基因突变检测呈阴性。此外，来自欧洲和美国的19名家族性和50名散发性肢端肥大症/垂体腺瘤患者也被纳入研究。主要结果测量：我们分析了垂体腺瘤和MEN 1样特征个体的生殖系CDKN 1B/p27（Kip 1）突变。一个杂合的19-bp重复（c.59_77dup19）导致截短的蛋白产物，在一名疑似MEN 1表型、垂体腺瘤、类癌肿瘤的荷兰患者中鉴定出，甲状旁腺功能亢进36例，占2.8%。在家族性或散发性肢端肥大症/垂体腺瘤patients.Conclusions：我们的研究结果支持以前的发现，生殖系CDKN 1B/p27（Kip 1）突变易患人类MEN 1样疾病。然而，这种突变在疑似MEN 1病例中不常见，在家族性或散发性肢端肥大症/垂体腺瘤患者中罕见或不存在。
Context: Germline mutations in the MEN1 gene predispose to multiple endocrine neoplasia type 1 (MEN1) syndrome, but in up to 20-25% of clinical MEN1 cases, no MEN1 mutations can be found. Recently, a germline mutation in the CDKN1B gene, encoding p27(Kip1), was reported in one suspected MEN1 family with two acromegalic patients.Objective: Our objective was to evaluate the role of CDKN1B/p27(Kip1) in human tumor predisposition in patients clinically suspected of MEN1 but testing negative for MEN1 germline mutation as well as in familial and sporadic acromegaly/pituitary adenoma patients.Design: Genomic DNA was analyzed for germline mutations in the CDKN1B/p27(Kip1) gene by PCR amplification and direct sequencing. Setting: The study was conducted at nonprofit academic research and medical centers.Patients: Thirty-six Dutch and one German suspected MEN1 patient, who previously tested negative for germline MEN1 gene mutations, were analyzed. In addition, 19 familial and 50 sporadic acromegaly/pituitary adenoma patients from Europe and the United States were included in the study.Main Outcome Measures: We analyzed germline CDKN1B/p27(Kip1) mutations in individuals with pituitary adenoma and MEN1-like features.Results: A heterozygous 19-bp duplication (c.59_77dup19) leading to a truncated protein product was identified in one Dutch patient with suspected MEN1 phenotype, pituitary adenoma, carcinoid tumor, and hyperparathyroidism (one of 36, 2.8%). No mutations were detected in either familial or sporadic acromegaly/pituitary adenoma patients.Conclusions: Our results support the previous finding that germline CDKN1B/p27(Kip1) mutations predispose to a human MEN1-like condition. However, such mutations appear uncommon in suspected MEN1 cases and rare or nonexistent in familial or sporadic acromegaly/pituitary adenoma patients.