Mutant TP53 in duodenal samples of pancreatic juice from patients with pancreatic cancer or high-grade dysplasia.
Mutant TP53 in duodenal samples of pancreatic juice from patients with pancreatic cancer or high-grade dysplasia.
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DOI：
10.1016/j.cgh.2012.11.016
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发表时间：
2013-06
影响因子：
12.6
通讯作者：
Goggins, Michael
中科院分区：
文献类型：
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作者：
Kanda, Mitsuro;Sadakari, Yoshihiko;Borges, Michael;Topazian, Mark;Farrell, James;Syngal, Sapna;Lee, Jeffrey;Kamel, Ihab;Lennon, Anne Marie;Knight, Spencer;Fujiwara, Sho;Hruban, Ralph H.;Canto, Marcia Irene;Goggins, Michael
影像学检查可以识别胰腺肿瘤性囊肿，但不能识别显微镜下的异型增生。我们研究了在分泌素刺激的胰液的十二指肠样品中可以检测到枯萎突变TP 53，以及该测定是否可以用于筛查高度异型增生和浸润性胰腺癌。我们确定了突变型TP 53在显微解剖的胰腺上皮内瘤变（PanIN）、导管内乳头状粘液性肿瘤（IPMN）和浸润性腺癌中的患病率。通过数字高分辨率熔解曲线分析和分泌素刺激的胰液样品的测序来定量TP 53突变，所述胰液样品收集自参加胰腺癌筛查试验的180名受试者的胰腺;患者是因为家族性和/或遗传性胰腺癌易感性而参加的，或作为对照。在9.1%的中级IPMN（2/22）、17.8%的PanIN-2（8/45）、38.1%的高级IPMN（8/21）、47.6%的PanIN-3（10/21）和75%的浸润性胰腺腺癌（15/20）中发现TP 53突变;在PanIN-1病变或低级IPMN中未发现TP 53突变。在29/43例胰腺导管腺癌患者（67.4%灵敏度; 95%置信区间，0.52 - 0.80）和4/8例高级别病变（PanIN-3和高级别IPMN）患者的十二指肠胰液样本中检测到TP 53突变。在来自58名对照或55名筛选个体的样本中没有发现TP 53突变，而没有晚期病变的证据。我们检测到突变TP 53分泌素刺激的胰液样本中收集的高度异型增生或浸润性胰腺癌患者的胰腺。突变型TP 53的检测可能会被开发出来，以改善胰腺癌和高度异型增生的诊断和筛查。clinicaltrials.gov（NCT 00438906、NCT 00714701）
Imaging tests can identify patients with pancreatic neoplastic cysts but not microscopic dysplasia. We investigated wither mutant TP53 can be detected in duodenal samples of secretin-stimulated pancreatic juice, and whether this assay can be used to screen for high-grade dysplasia and invasive pancreatic cancer. We determined the prevalence of mutant TP53 in microdissected pancreatic intraepithelial neoplasias (PanINs), intraductal papillary mucinous neoplasms (IPMNs), and invasive adenocarcinomas. TP53 mutations were quantified by digital high-resolution melt-curve analysis and sequencing of secretin-stimulated pancreatic juice samples, collected from duodena of 180 subjects enrolled in Cancer of the Pancreas Screening trials; patients were enrolled because of familial and/or inherited predisposition to pancreatic cancer, or as controls. TP53 mutations were identified in 9.1% of intermediate-grade IPMNs (2/22), 17.8% of PanIN-2 (8/45), 38.1% of high-grade IPMNs (8/21), 47.6% of PanIN-3(10/21), and 75% of invasive pancreatic adenocarcinomas (15/20); no TP53 mutations were found in PanIN-1 lesions or low-grade IPMNs. TP53 mutations were detected in duodenal samples of pancreatic juice from 29/43 patients with pancreatic ductal adenocarcinoma (67.4% sensitivity; 95% confidence interval, 0.52−0.80) and 4/8 patients with high-grade lesions (PanIN-3 and high-grade IPMN). No TP53 mutations were identified in samples from 58 controls or 55 screened individuals without evidence of advanced lesions. We detected mutant TP53 in secretin-stimulated pancreatic juice samples collected from duodena of patients with high-grade dysplasia or invasive pancreatic cancer. Tests for mutant TP53 might be developed to improve the diagnosis of and screening for pancreatic cancer and high-grade dyplasia. clinicaltrials.gov (NCT00438906, NCT00714701)
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DOI：
10.1158/1055-9965.epi-08-0630
发表时间：
2008-12
期刊：
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
影响因子：
--
作者：
Brune K;Hong SM;Li A;Yachida S;Abe T;Griffith M;Yang D;Omura N;Eshleman J;Canto M;Schulick R;Klein AP;Hruban RH;Iacobuzio-Donohue C;Goggins M
通讯作者：
Goggins M
影响因子：
17.1
作者：
Leary RJ;Kinde I;Diehl F;Schmidt K;Clouser C;Duncan C;Antipova A;Lee C;McKernan K;De La Vega FM;Kinzler KW;Vogelstein B;Diaz LA Jr;Velculescu VE
通讯作者：
Velculescu VE
影响因子：
9.8
作者：
Poley, J. W.;Kluijt, I.;Bruno, M. J.
通讯作者：
Bruno, M. J.
影响因子：
2.9
作者：
Kaino, M;Kondoh, S;Okita, K
通讯作者：
Okita, K
DOI：
10.1158/1078-0432.ccr-09-0004
发表时间：
2009-12-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Shi C;Klein AP;Goggins M;Maitra A;Canto M;Ali S;Schulick R;Palmisano E;Hruban RH
通讯作者：
Hruban RH