Methylation of p16 gene promoter in human pheochromocytomas and paragangliomas / 中华内分泌代谢杂志

ABSTRACT

Objective To elucidate gene mutation and promoter methylation changes of p16 gene in pheochromocytomas (PHEO) and paragangliomas (PGL) and to assess its relation with tumor clinical characters. Methods A total of 34 tumors (20 PHEO, 14 PG L, 15 benign, 19 malignant) were collected.Direct sequencing of p16 gene after PCR was performed to analyze genetic alterations. Hypermethylation of p16 gene promoter CpG island was analyzed by methylation specific PCR(MSP). In addition, mRNA expression was detected by RT-PCR. Results Homozygous deletion and gene mutation were not observed in 34 PHEO and PGL. Aberrant methylation of p16 gene promoter CpG island was found in 35.3% (12 of 34 tumors, 3 PHEO, 9 PGL). The p16 promoter hypermethylation in PGL was significantly higher than PHEO (P=0. 005). The higher p16 promoter hypermethylation was associated with malignant behavior, tumor number, and younger age at presentation, but no statistical significance, due to the limited number of cases. The p16 mRNA expression in malignant cases was lower than in benign tumors(0.83±0.65 vs 1.12±0.81 ,P=0.278). Conclusion p16 gene homozygous deletion and mutation were not frequent in PHEO and PGL. The promoter hypermethylation is mainly attributed to inactivation of the p16 gene.