胰岛素瘤频发MEN-1抑癌基因及22q的杂合缺失及其意义

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40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22号染色体长臂(22q)的杂合缺失(LOH)。结果40．0％的肿瘤发生MEN-1的LOH,75．0％的肿瘤发生22q的LOH。22q12(D22S929与D22S280之间)和22q13．3是LOH的2个频发区域,分别占30个22qLOH的37．0％(11／30)和47．0％(14／30)。在D22S280位点,有8个肿瘤标本发生D22S280LOH,但无一例发生MEN-1 LOH,而无D22S280 LOH的30个肿瘤标本中,有14个发生MEN-1 LOH(47．0％)(P=0．016)。在第2个频发区中,14个发生LOH的肿瘤有6个(43．0％)为恶性,26个无LOH肿瘤中有2个(8．0％)为恶性(P=0．0088)。结论在D22S280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22q13．3 LOH可能与肿瘤恶性相关。

Frequent loss of heterozygosity at MEN-1 gene and chromosome 22q in insulinomas and its significance

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