PURPOSE: Neuroblastoma is an embryonal tumor of neuroectodermal cells. Patients with metastatic neuroblastoma have a poor survival rate, which has led to numerous efforts to develop prognostic markers. Cancer/testis-specific antigens MAGE-A1 and MAGE-A3 genes were proposed as minimal residual disease (MRD) markers in neuroblastoma, but its usefulness for this purpose is rather limited. METHODS: We studied 47 primary neuroblastoma tumors. RNA was extracted and cDNA was prepared by reverse transcription. Detection of the MAGE-A1 expression was done by hybridization of the RT-PCR products. We used methylation-specific-PCR to perform the epigenetic studies. RESULTS: We studied the MAGE-A1 and MAGE-A3 expressions, and the MAGE-A1 expression showed significant association with tumor stage, absence of bone marrow infiltration and survival. A multivariate analysis enabled us to conclude that the MAGE-A1 expression represents a new independent predictive factor, which is independent of N-Myc amplification (P value = 0.000), age at diagnosis (P value = 0.002) or tumoral stage (P value = 0.024). Considering the epigenetic regulation of MAGE-A1, we analyzed its methylation profile, and found a significant association with its expression in tumor cells. Moreover, we found tumors that failed to show the MAGE-A1 expression despite the hypomethylated sequence, and corresponded to advanced neuroblastoma that might share another mechanism involved in MAGE-A1 silencing. Given the association described between genome-wide hypomethylation and microsatellite instability, we determined the MSI status of tumor samples, finding a significant correlation with the MAGE-A1 expression and, more specifically, with the hypomethylated status of this gene only in female patients. CONCLUSION: We conclude that the MAGE-A1 expression is associated with good prognosis in neuroblastoma.
PURPOSE:Neuroblastoma is an embryonal tumor of neuroectodermal cells. Patients with metastatic neuroblastoma have a poor survival rate, which has led to numerous efforts to develop prognostic markers. Cancer/testis-specific antigens MAGE-A1 and MAGE-A3 genes were proposed as minimal residual disease (MRD) markers in neuroblastoma, but its usefulness for this purpose is rather limited. METHODS: We studied 47 primary neuroblastoma tumors. RNA was extracted and cDNA was prepared by reverse transcription. Detection of the MAGE-A1 expression was done by hybridization of the RT-PCR products. We used methylation-specific-PCR to perform the epigenetic studies. RESULTS: We studied the MAGE-A1 and MAGE-A3 expressions, and the MAGE-A1 expression showed significant association with tumor stage, absence of bone marrow infiltration and survival. A multivariate analysis enabled us to conclude that the MAGE-A1 expression represents a new independent predictive factor, which is independent of N-Myc amplification (P value = 0.000), age at diagnosis (P value = 0.002) or tumoral stage (P value = 0.024). Considering the epigenetic regulation of MAGE-A1, we analyzed its methylation profile, and found a significant association with its expression in tumor cells. Moreover, we found tumors that failed to show the MAGE-A1 expression despite the hypomethylated sequence, and corresponded to advanced neuroblastoma that might share another mechanism involved in MAGE-A1 silencing. Given the association described between genome-wide hypomethylation and microsatellite instability, we determined the MSI status of tumor samples, finding a significant correlation with the MAGE-A1 expression and, more specifically, with the hypomethylated status of this gene only in female patients. CONCLUSION: We conclude that the MAGE-A1 expression is associated with good prognosis in neuroblastoma.
Authors: Edward F Attiyeh; Wendy B London; Yael P Mossé; Qun Wang; Cynthia Winter; Deepa Khazi; Patrick W McGrady; Robert C Seeger; A Thomas Look; Hiroyuki Shimada; Garrett M Brodeur; Susan L Cohn; Katherine K Matthay; John M Maris Journal: N Engl J Med Date: 2005-11-24 Impact factor: 91.245
Authors: D Rimoldi; S Salvi; D Reed; P Coulie; V C Jongeneel; E De Plaen; F Brasseur; A M Rodriguez; T Boon; J C Cerottini Journal: Int J Cancer Date: 1999-09-09 Impact factor: 7.396
Authors: Jie Zhang; Jian Yu; Jun Gu; Bao Mei Gao; Ying Jun Zhao; Peng Wang; Hong Yu Zhang; Jing De Zhu Journal: Cell Res Date: 2004-08 Impact factor: 25.617
Authors: E Schultz-Thater; A Juretic; P Dellabona; U Lüscher; W Siegrist; F Harder; M Heberer; M Zuber; G C Spagnoli Journal: Int J Cancer Date: 1994-11-01 Impact factor: 7.396
Authors: Jessica A Hemminger; Amanda Ewart Toland; Thomas J Scharschmidt; Joel L Mayerson; Denis C Guttridge; O Hans Iwenofu Journal: Mod Pathol Date: 2014-01-24 Impact factor: 7.842
Authors: Otavia L Caballero; Qi Zhao; Donata Rimoldi; Brian J Stevenson; Suzanne Svobodová; Sylvie Devalle; Ute F Röhrig; Anna Pagotto; Olivier Michielin; Daniel Speiser; Jedd D Wolchok; Cailian Liu; Tanja Pejovic; Kunle Odunsi; Francis Brasseur; Benoit J Van den Eynde; Lloyd J Old; Xin Lu; Jonathan Cebon; Robert L Strausberg; Andrew J Simpson Journal: PLoS One Date: 2010-09-16 Impact factor: 3.240
Authors: K Beiske; S A Burchill; I Y Cheung; E Hiyama; R C Seeger; S L Cohn; A D J Pearson; K K Matthay Journal: Br J Cancer Date: 2009-04-28 Impact factor: 7.640
Authors: Dimitrios Balafoutas; Axel zur Hausen; Sebastian Mayer; Marc Hirschfeld; Markus Jaeger; Dominik Denschlag; Gerald Gitsch; Achim Jungbluth; Elmar Stickeler Journal: BMC Cancer Date: 2013-06-03 Impact factor: 4.430