Mutation of the PTEN gene in advanced cervical cancer correlated with tumor progression and poor outcome after radiotherapy

晚期宫颈癌放疗后治疗的改进需要对其生物学行为有更好的了解。位于染色体10q23.3的候选抑癌基因PTEN MMAC TEP(PTEN)是新近发现的一种抑癌基因，在多种不同类型的人类肿瘤中经常发生突变。相比之下，在宫颈癌中发现了罕见的PTEN基因突变。本研究的目的是确定PTEN基因突变是否导致晚期宫颈癌基因组改变的增加，并确定PTEN基因突变与放疗后患者预后的关系。我们对50例原发晚期宫颈癌(IIIB期37例，IVA期13例)进行了明确的放射治疗标本的检测，采用基于聚合酶链式反应的分析、SSCP和直接测序。50例患者中有8例(16%)PTEN基因发生突变，其中2例为III期，6例为IV期。野生型与突变型PTEN患者的III、IV期差异有统计学意义(P=0.002)。肿瘤大小野生型为6±2.1 cm，突变型为8.5±2 cm(P=0.009)。野生型与突变型PTEN患者的生存率差异有统计学意义(P=0.009)。本研究结果提示，PTEN基因突变率随着肿瘤的进展而增加，PTEN基因可能在宫颈癌的进展和治疗结果中发挥作用。

Improvement of management of advanced cervical cancer after radiotherapy requires a better understanding of its biological behavior. PTEN MMAC TEP (PTEN), a candidate tumor suppressor gene located at chromosome 10q23.3 was recently identified and found to be frequently mutated in several different types of human tumors. In contrast rare mutations of the PTEN gene have been reported in cervical cancer. The aim of this study was to determine whether mutation of PTEN leads to increase genomic alteration in advanced cervical carcinoma and to identify the correlation between mutation of PTEN and patient outcome after radiotherapy. We examined 50 primary advanced cervical carcinomas (37 patients of Stage IIIB.13 patients of Stage IVA) treated with definitive radiotherapy specimens using a PCR-based assay followed by SSCP and direct sequencing. The PTEN gene was mutated in 8 of the 50 (16%) patients (2 of Stage III, and 6 of Stage IV). There was a significant difference in Stage III versus IV between the wild-type PTEN patients and mutant PTEN patients (P=0.002). The tumor size was 6±2.1 cm in the wild-type PTEN tumors versus 8.5±2 cm in the mutant PTEN tumors (P=0.009). In addition, there was a significant difference in survival between the wild-type PTEN patients and mutant PTEN patients (P=0.009). The results of this study suggest that the PTEN gene mutation rate increases with tumor progression, and that the PTEN gene may play a role in both progression of cervical carcinoma and treatment outcome.