Putative tumor suppressor loci at 6q22 and 6q23-q24 are involved in the malignant progression of sporadic endocrine pancreatic tumors
Putative tumor suppressor loci at 6q22 and 6q23-q24 are involved in the malignant progression of sporadic endocrine pancreatic tumors
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DOI：
10.1016/s0002-9440(10)64658-5
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发表时间：
2001-06-01
影响因子：
6
通讯作者：
Komminoth, P
中科院分区：
文献类型：
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作者：
Barghorn, A;Speel, EJM;Komminoth, P
我们之前对散发性内分泌胰腺肿瘤（EPTs）的比较基因组杂交研究发现，11q、3p和6q染色体经常丢失，本研究的目的是评估6q丢失在散发性内分泌胰腺肿瘤发生中的重要性，并缩小等位基因缺失的最小区域。采用多模式方法，结合基于聚合酶链反应的等位基因分型、双靶荧光原位杂交和比较基因组杂交，对来自93例患者的109例散发性ept进行了分析。9个多态性微卫星标记（6q13至6q25q27）被调查，显示62.2%的患者存在杂合性缺失（LOH）。LOH在直径小于2 cm的肿瘤中比小于2 cm的肿瘤更常见，恶性肿瘤比良性肿瘤更常见。我们能够将最小的等位基因缺失区域缩小到6q22.1 （D6S262）和6q23-q24 (D6S310-UTRN)， loh频率分别为50.0%和41.2 - 56.3%。使用三种位点特异性探针（6q21、6q22和6q27）以及着丝粒6特异性探针对46个ept进行荧光原位杂交分析，发现6号染色体完全缺失，尤其是在转移性疾病中。我们的结论是，在6q上发现的两个热点可能含有推测的肿瘤抑制基因，不仅参与了肿瘤的发生，而且可能参与了散发性ept的恶性和转移进展。
Our previous comparative genomic hybridization study on sporadic endocrine pancreatic tumors (EPTs) revealed frequent losses on chromosomes 11q, 3p, and 6q, The aim of this study was to evaluate the importance of 6q losses in the oncogenesis of sporadic EPTs and to narrow down the smallest regions of allelic deletion. A multimodal approach com bining polymerase chain reaction-based allelotyping, double-target fluorescence in situ hybridization, and comparative genomic hybridization was used in a collection of 109 sporadic EPTs from 93 patients. Nine polymorphic microsatellite markers (6q13 to 6q25q27) were investigated, demonstrating a loss of heterozygosity (LOH) in 62.2% of the patients. A LOH was significantly more common in tumors >2 cm in diameter than below this threshold as well as in malignant than in benign tumors. We were able to narrow down the smallest regions of allelic deletion at 6q22.1 (D6S262) and 6q23-q24 (D6S310-UTRN) with LOH-frequencies of 50.0% and 41.2 to 56.3%, respectively. Several promising tumor suppressor candidates are located in these regions, Additional fluorescence in situ hybridization analysis on 46 EPTs using three locus-specific probes (6q21, 6q22, and 6q27) as well as a centromere 6-specific probe revealed complete loss of chromosome 6 especially in metastatic disease, We conclude that the two hot spots found on 6q may harbor putative tumor suppressor genes involved not only in the oncogenesis but maybe also in the malignant and metastatic progression of sporadic EPTs.