During the course of our study Neupane and colleagues publis

During the course of our study, Neupane and colleagues published their work in which they SBI-0206965 identified MeCP2 as a frequently amplified oncogene (Neupane et al., 2016). Our work is similar to theirs in that both studies demonstrate the oncogenetic function of MeCP2. Oncogenesis is a multiple-factor and -stage network regulatory process, involving in many different types of signaling pathways. Neupane and colleagues found MeCP2 activates the MAPK and PI3K signaling in breast cancer, cervical cancer and lung cancer. However, our work is different from theirs, not only because we characterized the precise role of MeCP2 in GC that has not been studied before, but, more importantly, because we revealed different molecular mechanism of MeCP2 regulation in GC.
Funding sources This work was supported by the National Nature Science Foundation of China (31400730 and 81401137), China Postdoctoral Science Foundation (2013M542358), Shaanxi Province Natural Science Foundation (2014JM4122), Xi\'an Jiaotong University Biomedical Sharing Platform Project (2015FWPT-14), Shaanxi Province Social Development Of Science and Technology Project (2016SF-190), and Yanan City Science and Technology Research Development Planning Project (2016KS-06).
Conflicts of interest
Author contributions
Acknowledgments
Introduction Nephroblastoma (Wilms\' tumor) is an embryonal kidney malignancy. It is the most commonly diagnosed renal tumor in children, but rarely occurs in adults. The annual incidence rate of nephroblastoma is about 7–10 cases per million in children younger than 15years old, making up 6–7% of all childhood cancers (Ko and Ritchey, 2009). The incidents vary among the different ethnic groups, with the highest rates found in black Africana and the lowest in Asians (Ko and Ritchey, 2009). The variation in incident rates reflected implication of genetic factors in the aetiology of the disease. It was estimated that nephroblastoma affected 3.3 in one million children between 2002 and 2010 in China (Bao et al., 2013). Nephroblastoma is highly responsive to treatments, with a relatively favorable prognosis. The long term survival for regional and metastatic disease is over 90% and 75%, respectively (Ko and Ritchey, 2009; Szychot et al., 2014). However, there is still room for improvement in risk prediction and management of the disease. Approximately, 10%–15% of nephroblastomas are related to germline pathogenic variants or epigenetic alterations formed in the early stage of embryogenesis (Dome and Huff, 1993). Roughly 1%–2% of cases have at least one relative also developed Wilms\' tumor. Germline genetic and epigenetic variations are most frequently identified in Wilms\' Tumor 1 (WT1) gene and the 11p15.5 locus (Dome and Huff, 1993) in patients with Wilms\' tumor. In addition, genetic aberrations in other genes, including VHL, PBRM1, BAP1, may be implicated in the tumorigenesis of kidney cancers (Tan et al., 2015). Although pathogenic genetic alterations are clear in some families, they remain unknown for the majority of individuals. Therefore, additional relevant variants in other genes should be further explored. BRCA1-associated RING domain protein 1 (BARD1) is encoded by the human BARD1 gene, which is known to interact with breast cancer susceptibility gene 1 (BRCA1) (Wu et al., 1996; Irminger-Finger and Jefford, 2006; Irminger-Finger et al., 2016). BARD1 shares homologies with BRCA1 in primary structure within the N-terminal RING finger motif and two C-terminal BRCA1 carboxy-terminal (BRCT) domains (Wooster et al., 1994). These two proteins form a heterodimer through their N-terminalRING finger mofis (Meza et al., 1999). BARD1 is able to regulate the tumor-suppressor function of BRCA1 (Greenberg et al., 2006; Kim et al., 2006; Simons et al., 2006; Irminger-Finger et al., 2016). Disruption of the BARD1/BRCA1 interaction may impair BRCA1 tumor suppression functions. BARD1 itself is also a tumor suppressor (Irminger-Finger et al., 2016). Mice with conditional deletion of BARD1 in mammary epithelial cells developed breast cancer (Shakya et al., 2008). Moreover, structure-affecting mutations in the BARD1 gene were frequently identified in breast, ovarian, and uterine cancers (Irminger-Finger and Jefford, 2006). Because of the biological importance of BARD1, single nucleotide polymorphisms (SNPs) that alter its function or expression may modify susceptibility to cancer. A previous genome-wide association study (GWAS) found that BARD1 gene polymorphisms (rs7585356 G>A, rs6435862 T>G and rs3768716 A>G) were associated with neuroblastoma susceptibility (Capasso et al., 2009). Given the importance of BARD1 in cancer, we investigated whether the three SNPs confer nephroblastoma susceptibility in a Southern Chinese population consisting of 145 cases and 531 controls.