Genetic analyses of the HRPT2 gene in primary hyperparathyroidism:: Germline and somatic mutations in familial and sporadic parathyroid tumors
Genetic analyses of the HRPT2 gene in primary hyperparathyroidism:: Germline and somatic mutations in familial and sporadic parathyroid tumors
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DOI：
10.1210/jc.2004-0294
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发表时间：
2004-11-01
影响因子：
5.8
通讯作者：
Marcocci, C
中科院分区：
文献类型：
--
作者：
Cetani, F;Pardi, E;Marcocci, C
我们通过杂合性缺失分析和直接测序研究了一个患有甲状旁腺功能亢进-颌骨肿瘤综合征（HPT-JT）的家族和三个患有家族性孤立性原发性甲状旁腺功能亢进（FIHP）的家族中HRPT 2基因的参与情况。7例散发性甲状旁腺癌患者和35例无原发性甲状旁腺功能亢进或HPT-JT家族史的甲状旁腺腺瘤患者也进行了研究。在三个FIHP家族中的一个家族中，在内含子1的供体剪接位点发现了一个种系杂合替换G到A。在HPT-JT家族中未发现突变。7例甲状旁腺癌患者中有4例发现HRPT 2体细胞突变，其中2例为外显子2未报道的移码突变（195 insT和195 insA）。与最近的研究结果一致，7例散发性甲状旁腺癌患者中有2例发生生殖细胞突变。四个腺瘤显示HRPT 2杂合性丢失，而体细胞HRPT 2突变被发现在一个。总之，我们为HRPT 2基因突变和散发性甲状旁腺癌之间的强相关性提供了额外的证据。7例散发性甲状旁腺癌患者中有2例携带HRPT 2种系突变，这一发现表明他们可能患有隐匿性HPT-JT。我们的研究结果也证实了在FIHP家族中检测HRPT 2基因的必要性。
We investigated the involvement of the HRPT2 gene by loss of heterozygosity analysis and direct sequencing in a kindred with hyperparathyroidism- jaw tumor syndrome (HPT-JT) and three kindreds with familial isolated primary hyperparathyroidism (FIHP). Seven patients with sporadic parathyroid cancers and 35 with parathyroid adenomas with no family history of primary hyperparathyroidism or HPT-JT were also studied. A germline heterozygous substitution G to A was found in the donor splice site of intron 1 in one of the three FIHP families. No mutations were identified in the HPT-JT kindred. A somatic HRPT2 mutation was found in four of seven patients with parathyroid cancers, two of which were unreported frameshift mutations (195insT and 195insA) in exon 2. Consistent with recent findings, two of seven patients with sporadic parathyroid cancer had germline mutations. Four adenomas showed loss of heterozygosity at HRPT2, whereas a somatic HRPT2 mutation was found in one. In conclusion, we provide additional evidence for a strong association between HRPT2 gene mutations and sporadic parathyroid cancer. The finding that two of the seven patients with sporadic parathyroid cancer carried an HRPT2 germline mutation suggests that they might have occult HPT-JT. Our results also confirm the need for testing HRPT2 gene in FIHP families.