Wnt signaling promoter hypermethylation distinguishes lung primary adenocarcinomas from colorectal metastasis to the lung

作者: Moying Tang , Juan Torres-Lanzas , Fernando Lopez-Rios , Manel Esteller , Montserrat Sanchez-Cespedes

DOI: 10.1002/IJC.22211

关键词: CDH1Wnt signaling pathwayLung cancerMLH1DNA methylationPromoterCarcinogenesisCancer researchMethylationMedicine

摘要: Promoter hypermethylation is responsible for gene inactivation during carcinogenesis. It has been proposed that there some degree of specificity in the set genes become altered by this mechanism distinct tumor types. To understand whether promoter may differentiate site origin, 49 lung adenocarcinomas from 31 primaries and 18 metastases colorectal primaries, respectively, were tested presence alteration APC, CDH1, DAPK, GSTP1, MLH1, MGMT, P14, P16, RARβ2, RASSF1, sFRP1 WIF-1 genes. A profile was apparent 2 groups tumors frequencies at WIF-1, involved Wnt signaling, CDH1 significantly higher than whereas methylation APC more common primary adenocarcinomas. Some showed concomitant inactivation, indicating multiple DNA events must have occurred to definitively down-regulate signaling through Wnt. However, tended be mutually exclusive (Fisher's exact test, p = 0.006), suggesting a similar role In conclusion, we propose contribute discrimination metastasis lung, report simultaneous promoters signaling. This biological consequences © 2006 Wiley-Liss, Inc.

参考文章(21)
Heffelfinger-Juttner J, Nystrom Js, Weiner Jm, Irwin Le, Bateman, Wolf Rm, Metastatic and histologic presentations in unknown primary cancer. Seminars in Oncology. ,vol. 4, pp. 53- 58 ,(1977)
Jen-Chih Hsieh, Laurent Kodjabachian, Martha L. Rebbert, Amir Rattner, Philip M. Smallwood, Cynthia Harryman Samos, Roel Nusse, Igor B. Dawid, Jeremy Nathans, A new secreted protein that binds to Wnt proteins and inhibits their activites Nature. ,vol. 398, pp. 431- 436 ,(1999) , 10.1038/18899
Manel Esteller, Manel Esteller, Stephen B. Baylin, James G. Herman, Paul G. Corn, A Gene Hypermethylation Profile of Human Cancer Cancer Research. ,vol. 61, pp. 3225- 3229 ,(2001)
Montserrat Sanchez-Cespedes, Manel Esteller, Li Wu, Homaira Nawroz-Danish, George H Yoo, Wayne M Koch, Jin Jen, James G Herman, David Sidransky, None, Gene Promoter Hypermethylation in Tumors and Serum of Head and Neck Cancer Patients Cancer Research. ,vol. 60, pp. 892- 895 ,(2000)
Biao He, Noemi Reguart, Liang You, Julien Mazieres, Zhidong Xu, Amie Y Lee, Iwao Mikami, Frank McCormick, David M Jablons, Blockade of Wnt-1 signaling induces apoptosis in human colorectal cancer cells containing downstream mutations Oncogene. ,vol. 24, pp. 3054- 3058 ,(2005) , 10.1038/SJ.ONC.1208511
Giulio Rossi, Bruno Murer, Alberto Cavazza, Lorena Losi, Pamela Natali, Alessandro Marchioni, Mario Migaldi, Giovanni Capitanio, Elisabeth Brambilla, Primary mucinous (so-called colloid) carcinomas of the lung - A clinicopathologic and immunohistochemical study with special reference to CDX-2 homeobox gene and MUC2 expression The American Journal of Surgical Pathology. ,vol. 28, pp. 442- 452 ,(2004) , 10.1097/00000478-200404000-00003
Germaine M. Caldwell, Carolyn Jones, Karl Gensberg, Shamem Jan, Robert G. Hardy, Philip Byrd, Shaheen Chughtai, Yvonne Wallis, Glenn M. Matthews, Dion G. Morton, The Wnt Antagonist sFRP1 in Colorectal Tumorigenesis Cancer Research. ,vol. 64, pp. 883- 888 ,(2004) , 10.1158/0008-5472.CAN-03-1346
Béatrice Eymin, Sylvie Gazzeri, Christian Brambilla, Elisabeth Brambilla, Mdm2 overexpression and p14(ARF) inactivation are two mutually exclusive events in primary human lung tumors. Oncogene. ,vol. 21, pp. 2750- 2761 ,(2002) , 10.1038/SJ.ONC.1205359