摘要
目的 探讨胰岛素瘤发病的可能机制 ,寻找鉴别胰岛素瘤良恶性的分子遗传学指标。方法 4 0个胰岛素瘤肿瘤标本 (8个恶性 ,32个良性 )经显微切割获取肿瘤组织和正常对照组织 ,并提取相应的基因组DNA。用聚合酶链反应 (PCR)检测MEN 1基因以及 2 2号染色体长臂 (2 2q)的杂合缺失 (LOH)。结果 4 0 0 %的肿瘤发生MEN 1的LOH ,75 0 %的肿瘤发生 2 2q的LOH。2 2q12 (D2 2S 92 9与D2 2S 2 80之间 )和 2 2q13 3是LOH的 2个频发区域 ,分别占 30个 2 2qLOH的 37 0 % (11/ 30 )和4 7 0 % (14 / 30 )。在D2 2S 2 80位点 ,有 8个肿瘤标本发生D2 2S 2 80LOH ,但无一例发生MEN 1LOH ,而无D2 2S2 80LOH的 30个肿瘤标本中 ,有 14个发生MEN 1LOH(47 0 % ) (P =0 0 16 )。在第 2个频发区中 ,14个发生LOH的肿瘤有 6个 (43 0 % )为恶性 ,2 6个无LOH肿瘤中有 2个 (8 0 % )为恶性(P =0 0 0 88)。结论 在D2 2S 2 80位点上发生LOH可能是一个与MEN 1基因无关的独立的胰岛素瘤致病因素。发生 2 2q13 3LOH可能与肿瘤恶性相关。
Objective To detecte whether loss of heterozygosity (LOH) at the MEN 1 locus as well as 22q occurs in sporadic insulinoma and if LOH can be used as a genetic marker to differentiate malignant and benign insulinomas Methods MEN 1 gene and 22q allelotyping were performed by PCR with microsatallite markers in DNA from microdissected normal and tumor tissues from archived or frozen insulinomas (8 malignant and 32 benign, from 38 patients) The significance was calculated using t test and Cochran Mantel Haenszel Statistics, P < 0 05 was considered significant Results Sixteen of the 40 insulinomas (40 0%) had MEN 1 LOH and 22q LOH was shown in 30 of the 40 tumors (75 0%) Eleven of the 30 tumors (37 0%) with 22q LOH had 22q12 LOH over a 3 cm region, whereas LOH in 14 tumors(47 0%) occurred at 22q13 3 Eight tumors with D22S 280 locus(22q12) LOH were shown without MEN 1 LOH while 14 of the 30 tumors without D22S280 LOH had MEN 1 LOH (0% vs 47%, P =0 016) Six of the 14 tumors (43 0%) with 22q13 3 LOH were malignant, whereas 2 of 26 tumors without 22q13 3 LOH (8 0%) are malignant ( P =0 0088) Conclusion MEN 1 gene LOH may contribute to a proportion of insulinomas, and 22q LOH occurs frequently in insulinomas D22S 280 (22q12) LOH may independently contribute to the tumorogenesis of sporadic insulinoams, whereas detecting 22q13 3 LOH in insulinomas can be a potential genetic marker to distinguish malignancy from benign tumors
出处
《中华医学杂志》
CAS
CSCD
北大核心
2004年第20期1705-1709,共5页
National Medical Journal of China
