Comparison of K-ras point mutation distributions in intraductal papillary-mucinous tumors and ductal adenocarcinoma of the pancreas
Comparison of K-ras point mutation distributions in intraductal papillary-mucinous tumors and ductal adenocarcinoma of the pancreas
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DOI：
10.1002/ijc.20084
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发表时间：
2004-06-10
影响因子：
6.4
通讯作者：
Kitajima, M
中科院分区：
文献类型：
--
作者：
Kitago, M;Ueda, M;Kitajima, M
导管内乳头状粘液瘤（IPMT）由不同组织学严重程度的细胞组成，表现为多个肿瘤位点；然而，这些病变是否表现出相同的遗传变化尚未明确。为了研究这一点，我们分析了参与我们研究的每个患者的多个IPMT病变中的K-ras突变，并将我们的发现与胰腺导管腺癌（DC）患者的发现进行了比较。20例IPMT标本和7例DC标本被切除，显微解剖并分析是否存在K-ras突变。然后用基因分析仪对突变基因进行测序。在80%的IPMT和100%的DC患者中观察到K-ras突变。在43.8%的IPMT和0%的DC患者的主要肿瘤中观察到2种以上的K-ras突变。66.7%和62.5%的IPMT患者在瘤周和分离病灶中分别观察到K-ras突变。所有IPMT患者的主要肿瘤和瘤周或分离病变之间至少有一个相同的突变。在分离病灶的IPMT患者中，40%观察到与主要肿瘤不同的突变。主肿瘤中存在2种以上K-ras突变的ipmt -癌患者的生存曲线优于存在1种以上K-ras突变的患者。IPMT患者主要肿瘤具有显著的遗传异质性，预后良好。(C) 2004 Wiley-Liss, Inc。
Intraductal papillary-mucinous tumors (IPMT) consist of cells with varying histologic degrees of severity and exhibit multiple tumor loci; however, whether or not these lesions exhibit the same genetic changes has not been clarified. To investigate this point, we analyzed K-ras mutations in multiple IPMT lesions from each patient enrolled in our study and compared our findings to those for patients with ductal adenocarcinoma of the pancreas (DC). Twenty IPMT specimens and 7 DC specimens were resected, microdissected and analyzed for the presence of K-ras mutations. The mutated genes were then sequenced using a genetic analyzer. K-ras mutations were observed in 80% of IPMT and 100% of DC patients. More than 2 types of K-ras mutation were observed in the main tumors of 43.8% of IPMT and 0% of DC patients. K-ras mutations in peritumoral and separated lesions were observed in 66.7% and 62.5% of IPMT patients, respectively. At least one identical mutation between the main tumor and the peritumoral or separated lesions was recognized in all of the IPMT patients with those lesions. Different mutations from those in the main tumor were observed in 40% of IPMT patients with separated lesions. The survival curve of IPMT-carcinoma patients with more than 2 types of K-ras mutation in the main tumor was better than that with one type of K-ras mutation. IPMT patients exhibit a remarkably genetic heterogeneity in main tumor and have good prognosis. (C) 2004 Wiley-Liss, Inc.