Molecular genetic analysis of ovarian serous cystadenomas
Molecular genetic analysis of ovarian serous cystadenomas
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DOI：
10.1038/labinvest.3700103
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发表时间：
2004-06-01
影响因子：
5
通讯作者：
Shih, IM
中科院分区：
文献类型：
--
作者：
Cheng, EJ;Kurman, RJ;Shih, IM
卵巢浆液性囊腺瘤是常见的卵巢病变，可能是浆液性交界性肿瘤的前兆，而浆液性交界性肿瘤又可进展为低级别浆液性癌。研究表明，低级别浆液性癌和浆液性交界性肿瘤的特点是BRAF或KRAS基因频繁突变，但这些基因在浆液性囊腺瘤中的突变状态以及浆液性囊腺瘤的克隆性质尚未得到充分研究。我们从 30 个连续的浆液性囊腺瘤中分离出囊肿衬里上皮，并分析了它们的 BRAF 和 KRAS 突变状态。所有标本中均检测到 BRAF 和 KRAS 野生型序列。使用人类雄激素受体基因作为多态性标记，我们还检查了上皮细胞的克隆状态！所有浆液性囊腺瘤中的细胞。根据甲基化模式，29 个信息丰富的样本中有 4 个（14%）是单克隆的。这些单克隆囊腺瘤比非克隆囊腺瘤显着（P 8 cm）。这些数据表明浆液性囊腺瘤不包含 BRAF 或 KRAS 基因突变，并且大多数浆液性囊腺瘤是多克隆的。因此，浆液性囊腺瘤似乎是由上皮包涵体增生性扩张而发展而来，其中一部分发生克隆/肿瘤转化。
Ovarian serous cystadenomas are common ovarian lesions that may be precursors of serous borderline tumors, which can in turn progress to low-grade serous carcinomas. It has been shown that low-grade serous carcinoma and serous borderline tumors are characterized by frequent mutations in BRAF or KRAS genes, but the mutational status of these genes in serous cystadenomas and the clonal nature of serous cystadenomas have not been fully investigated. We isolated cyst-lining epithelium from 30 consecutive serous cystadenomas, and analyzed their BRAF and KRAS mutational status. Wild-type sequences of BRAF and KRAS were detected in all specimens. Using the human androgen receptor gene as a polymorphic marker, we also examined the clonal status of epithelia! cells in all of the serous cystadenomas. Four of 29 (14%) informative specimens were monoclonal based on the methylation pattern. These monoclonal cystadenomas were significantly (P 8 cm) than the nonclonal cystadenomas. These data indicate that serous cystadenomas do not contain mutations in either BRAF or KRAS genes and that most serous cystadenomas are polyclonal. Accordingly, it appears that serous cystadenomas develop as a hyperplastic expansion from epithelial inclusions with a clonal/neoplastic transformation occurring in a subset of them.