Abstract OBJECTIVE: To investigate the mRNA expression and promoter methylation status of p73 gene in the peripheral blood of children with Wilms' tumor (WT), and their relationship. METHODS: Forty-five children with WT were selected as the case group, and 15 sex- and age- matched children (without malignancies) who visited the hospital for physical examination or other reasons were selected as the control group. Peripheral blood was collected from both groups. Real-time quantitative PCR and methylation-specific PCR were used to determine the mRNA expression level and promoter methylation status of p73 gene. Their relationship with clinicopathological features and the effect of promoter methylation on mRNA expression of p73 gene were analyzed in the case group. RESULTS: The relative quantity (RQ) of p73 mRNA in the case group was significantly higher than in the control group (3.2±0.9 vs 1.6±1.1; P<0.01). The positive rate of p73 gene promoter methylation in the case group was significantly lower than in the control group (20% vs 73%; P<0.01). In the case group, the RQ of p73 mRNA was significantly higher in children with methylated p73 gene promoter than in those with unmethylated p73 gene promoter (P<0.01). In children with methylated p73 gene promoter, the RQ of p73 mRNA was significantly higher in the case group than in the control group (P<0.01). In children with unmethylated p73 gene promoter, there was no significant difference in RQ of p73 mRNA between the case and control groups (P=0.810). CONCLUSIONS: Aberrant promoter methylation of p73 gene in peripheral blood is one of the gene expression regulations in children with WT, and it is related to the onset and development of WT. The p73 gene may play a role as oncogene in WT patients with p73 gene promoter methylation and mRNA overexpression is associated with promoter methylation status of p73 gene.
SONG Dong-Jian,YUE Li-Fang,ZHANG Da et al. Relationship between mRNA expression and promoter methylation status of p73 gene in peripheral blood among children with Wilms' tumor[J]. CJCP, 2013, 15(8): 638-643.
SONG Dong-Jian,YUE Li-Fang,ZHANG Da et al. Relationship between mRNA expression and promoter methylation status of p73 gene in peripheral blood among children with Wilms' tumor[J]. CJCP, 2013, 15(8): 638-643.
Murphy AJ, Pierce J, de Caestecker C, Taylor C, Anderson JR, Perantoni AO, et al. SIX2 and CITED1, markers of nephronic progenitor self-renewal, remain active in primitive elements of Wilms' tumor[J]. J Pediatr Surg, 2012, 47(6): 1239-1249.
[3]
Jha AK, Nikbakht M, Jain V, Sehgal A, Capalash N, Kaur J. Promoter hypermethylation of p73 and p53 genes in cervical cancer patients among north Indian population[J]. Mol Biol Rep, 2012, 39(9): 9145-9157.
[4]
Marabese M，Vikhanskaya F, Broggini M. p73: a chiaroscuro gene in cancer[J]. Eur J Cancer, 2007, 43(9): 1361-1372.
[5]
Gonzalez-Cano L, Herreros-Villanueva M, Fernandez-Alonso R, Ayuso-Sacido A, Meyer G, Garcia-Verdugo JM, et al. p73 deficiency results in impaired self renewal and premature neuronal differentiation of mouse neural progenitors independently of p53 [J]. Cell Death Dis, 2010, 1: e109.
[6]
Ye B, Wang X, Yang Z, Sun Z, Zhang R, Hu Y, et al. p53 and p73 expression in esophageal carcinoma correlate with clinicopathology of tumors[J]. Hepatogastroenterology, 2012, 59(119): 2192-2195.
[7]
Ma Y, Li Q, Cui W, Miao N, Liu X, Zhang W,et al. Expression of c-Jun, p73, Casp9, and N-ras in thymic epithelial tumors: relationship with the current WHO classification systems[J]. Diaqn Pathol, 2012, 7: 120.
[8]
Moll UM, Slade N. p63 and p73: roles in development and tumor formation[J]. Mol Cancer Res, 2004, 2(7): 371-386.
Douc-Rasy S, Barrois M, Echeynne M, Kaghad M, Blanc E, Raguenez G, et al. DeltaN-p73 alpha accumulates in human neuroblastic tumours[J] . Am J Pathol, 2002, 160(2): 631-639.
[11]
Ishimoto O, Kawahara C, Enjo K, Obinata M, Nukiwa T, Ikawa S. Possible oncogenic potential of DeltaNp73: a newly identified isoform of human p73[J]. Cancer Res, 2002, 62(3): 636-641.
[12]
Concin N, Becker K, Slade N, Erster S, Mueller-Holzner E, Ulmer H, et al. Transdominant ΔTAp73 isoforms are frequently up-regulated in Ovarian Cancer.Evidence for their role as epigenetic p53 inhibitors in vivo[J]. Cancer Res, 2004, 64(7): 2449-2460.
[13]
McKeon F, Melino G. Fog of war: the emerging p53 family[J]. Cell Cycle, 2007, 6(3): 229-232.
[14]
Ozono E, Komori H, Iwanaga R, Tanaka T, Sakae T, Kitamura H, et al. Tumor suppressor TAp73 gene specifically responds to deregulated E2F activity in human normal fibroblasts[J]. Genes Cells, 2012, 17(8): 660-672.
[15]
Melino G, Laurenzi VD, Vousden KH. p73: friend or foe in tumorigenesis[J]. Nat Rev Cancer, 2002, 2(8): 605-615.
[16]
Pei JH, Luo SQ, Zhong Y, Chen JH, Xiao HW, Hu WX. The association between non-Hodgkin lymphoma and methylation of p73[J]. Tumor Bio, 2011, 32(6): 1133-1138.
Abd El-Hamid TM, Mossallam GI, Sherisher MA. The Clinical Implications of Methylated p15 and p73 Genes in Adult Acute Lymphoblastic Leukemia[J]. J Egypt Natl Canc Inst, 2010, 22(3): 175-184.
[19]
Saito M, Nishikawa J, Okada T, Morishige A, Sakai K, Nakamura M, et al. Role of DNA methylation in the development of Epstein-Barr virus-associated gastric carcinoma[J]. J Med Virol, 2013, 85(1): 121-127.
[20]
Zhao Y, Fei C, Zhang X, Zhang Y, Guo J, Gu S, et al. Methylation of the p73 gene in patients with myelodysplastic syndromes: correlations with apoptosis and prognosis[J]. Tumor Biol, 2013, 34(1): 165-172.
[21]
Daskalos A, Logotheti S, Markopoulou S, Xinarianos G, Gosney JR, Kastania AN, et al. Global DNA hypomethylation-induced △Np73 transcriptional activation in non-small cell lung cancer[J]. Cancer Lett, 2011, 300(1): 79-86.
