The methylation status of RASSF1A promoter predicts responsiveness to chemotherapy and eventual cure in hepatoblastoma patients

作者: Shohei Honda , Masayuki Haruta , Waka Sugawara , Fumiaki Sasaki , Miki Ohira

DOI: 10.1002/IJC.23613

关键词:

摘要: Despite the progress of therapy, outcomes advanced hepatoblastoma patients who are refractory to standard preoperative chemotherapy remain unsatisfactory. To improve mortality rate, novel prognostic markers needed for better therapy planning. We examined methylation status 13 candidate tumor suppressor genes in 20 tumors by conventional methylation-specific PCR (MSP) and found hypermethylation 3 genes. analyzed these (RASSF1A, SOCS1 CASP8) 97 30.9, 33.0 15.5%, respectively. Univariate analysis showed that only RASSF1A but not other 2 predicted outcome, multivariate a weak contribution overall survival. Using quantitative MSP, we 44.3% tumors. CTNNB1 mutation was detected 67.0% While univariate demonstrated methylation, clinicopathological variables as factors, identified (p = 0.043; relative risk 9.39) disease stage 0.002; 7.67) independent factors. In survival 33 3B or 4, with unmethylated had than those methylated 0.035). may be promising molecular-genetic marker predict treatment outcome used stratify when clinical trials carried out.

参考文章(43)
Yener Koc, David P. Schenkein, Therapy of diffuse aggressive lymphomas Cancer treatment and research. ,vol. 99, pp. 47- 73 ,(1999) , 10.1007/978-0-585-38571-6_3
Ruthild G. Weber, Torsten Pietsch, Dietrich von Schweinitz, Peter Lichter, Characterization of genomic alterations in hepatoblastomas: A role for gains on chromosomes 8q and 20 as predictors of poor outcome American Journal of Pathology. ,vol. 157, pp. 571- 578 ,(2000) , 10.1016/S0002-9440(10)64567-1
Tal Teitz, Tie Wei, Marcus B. Valentine, Elio F. Vanin, Jose Grenet, Virginia A. Valentine, Frederick G. Behm, A. Thomas Look, Jill M. Lahti, Vincent J. Kidd, Caspase 8 is deleted or silenced preferentially in childhood neuroblastomas with amplification of MYCN Nature Medicine. ,vol. 6, pp. 529- 535 ,(2000) , 10.1038/75007
Reinhard Dammann, Chun Li, Jung-Hoon Yoon, Philip L. Chin, Steven Bates, Gerd P. Pfeifer, Epigenetic inactivation of a RAS association domain family protein from the lung tumour suppressor locus 3p21.3. Nature Genetics. ,vol. 25, pp. 315- 319 ,(2000) , 10.1038/77083
Jörg Fuchs, Jana Rydzynski, Dietrich Von Schweinitz, Udo Bode, Hartmut Hecker, Peter Weinel, Dietrich Bürger, Dieter Harms, Rudolf Erttmann, Karl Oldhafer, Hermann Mildenberger, , Pretreatment prognostic factors and treatment results in children with hepatoblastoma: a report from the German Cooperative Pediatric Liver Tumor Study HB 94. Cancer. ,vol. 95, pp. 172- 182 ,(2002) , 10.1002/CNCR.10632
Tadashi Matsunaga, Fumiaki Sasaki, Mutsuro Ohira, Kohei Hashizume, Akira Hayashi, Yutaka Hayashi, Hideo Mugishima, Naomi Ohnuma, Analysis of treatment outcome for children with recurrent or metastatic hepatoblastoma Pediatric Surgery International. ,vol. 19, pp. 142- 146 ,(2003) , 10.1007/S00383-002-0906-0
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)
Akira Nakagawara, Tsuyoshi Takato, Toshikazu Ushijima, Miki Ohira, Seiichiro Yamamoto, Masanobu Abe, Atsushi Kaneda, Yukiko Yagi, Yoshihiro Kitano, CpG Island Methylator Phenotype Is a Strong Determinant of Poor Prognosis in Neuroblastomas Cancer Research. ,vol. 65, pp. 828- 834 ,(2005)
Akira Nakagawara, Sachiyo Suita, Keiji Furuuchi, Toshinori Ozaki, Naomi Ohnuma, Tadashi Matsunaga, Eiso Hiyama, Kohei Hashizume, Fumiaki Sasaki, Michio Kaneko, Mitsuhiro Tada, Hiroshi Horie, Yoshio Watanabe, Hajime Takayasu, Yutaka Hayashi, Frequent deletions and mutations of the beta-catenin gene are associated with overexpression of cyclin D1 and fibronectin and poorly differentiated histology in childhood hepatoblastoma. Clinical Cancer Research. ,vol. 7, pp. 901- 908 ,(2001)