色素沉着息肉综合征患者肿瘤LKB1基因杂合性缺失及其对肿瘤易感性的研究

目的 研究色素沉着息肉综合征（Ｐｅｕｔｚ－Ｊｅｇｈｅｒｓ ｓｙｎｄｒｏｍｅ，ＰＪＳ）患者肿瘤的ＬＫＢ１基因杂合性缺失，探讨其肿瘤易感性机制。方法 以微分离技术分离６例与ＬＫＢ１连锁的色素沉着息肉综合征患者１４个肿瘤和相应正常组织的石蜡切片，提取ＤＮＡ，选择与ＬＫＢ１紧密连锁的Ｄ１９Ｓ８８６和Ｄ１９Ｓ５６５微卫星标志，经聚合酶链反应（ＰＣＲ）扩增，以测序仪检测和分析其杂合性缺失。结果 ５７％的易感肿

Loss of heterozygosity of LKB1 in tumors from Peutz-Jeghers syndrome patients and its cancer predisposing mechanism

Objective\ To study the loss of heterozygosity of LKB1 in tumors from Peutz Jeghers patients and to elucidate its tumorigenesis mechanism. Methods\ Fourteen tumors and corresponding normal paraffin embedded slides from 6 patients who were linked to LKB1 were microdissected and DNA were extracted. D19S886 and D19S565 microsatellites linked closely to LKB1 were PCR amplified and LOH was analyzed by DNA sequencer. Results\ LOH of LKB1 were detected in 57 % PJS tumors, including 3 colon cancers, 2 cervical adenocarcinoma, 1 hamartoma, adenoma polyp and breast cancer each. Conclusion\ LOH of LKB1 is a major mechanism underlying tumor predisposition to cancers of multiple organs in Peutz Jeghers patients. A hamartoma (adenoma) cancer sequence exists in Peutz Jeghers patients. Some hamartomas and adenomas (acquiring LOH of LKB1) is considered to be premaligant lesions. Intestinal adenoma might be a characteristics of some Peutz Jeghers patients.