Phosphatidylinositol-3-kinase α catalytic subunit gene somatic mutations in bronchopulmonary neuroendocrine tumours.
Phosphatidylinositol-3-kinase α catalytic subunit gene somatic mutations in bronchopulmonary neuroendocrine tumours.
复制标题
DOI：
10.3892/or.2012.2017
复制
发表时间：
2012-11
期刊：
影响因子：
4.2
通讯作者：
Fontanini G
中科院分区：
文献类型：
--
作者：
Capodanno A;Boldrini L;Alì G;Pelliccioni S;Mussi A;Fontanini G
支气管肺神经内分泌肿瘤（BP-NET）包括一系列肿瘤，包括典型类癌（TC）、非典型类癌（AC）、大细胞神经内分泌癌（LCNEC）和小细胞肺癌（SCLC），它们表现出相当不同的生物侵袭性和临床行为。已知磷脂酰肌醇-3-激酶α催化亚基（PIK 3CA）基因通过螺旋和催化结构域内的基因扩增、缺失或体细胞错义突变参与几种类型的人类癌症的发病机制。然而，PIK 3CA基因在BP-NET中的状态还有待探索。本研究旨在通过直接基因测序研究大量BP-NET中PIK 3CA基因的状态，并分析其与主要临床病理参数的相关性。据我们所知，我们首次在一系列190个BP-NET中证明了PIK 3CA基因的高频率体细胞错义突变（23.2%），包括75个TC，23个AC，17个LCNEC和75个SCLC。PIK 3CA基因在激酶结构域的突变频率（17.9%）高于螺旋结构域（5.3%）。当将PIK 3CA基因的突变状态与BP-NET患者的主要临床和病理特征进行比较时，我们发现PIK 3CA基因突变与BP-NET组织学之间存在显著相关性（P=0.011）。有趣的是，PIK 3CA基因突变的频率随着所有BP-NET的生物侵袭性而增加，除了LCNEC。总之，我们的研究结果表明，PIK 3CA基因突变可能在BP-NETs的肿瘤发生和侵袭性中起关键作用。PIK 3CA基因可能是治疗BP-NET患者的有效治疗策略的有利候选者。
Bronchopulmonary neuroendocrine tumours (BP-NETs) comprise a large spectrum of tumours including typical carcinoids (TCs), atypical carcinoids (ACs), large-cell neuroendocrine carcinomas (LCNECs) and small-cell lung carcinomas (SCLCs) that exhibit considerably different biological aggressiveness and clinical behaviours. The phosphatidylinositol-3-kinase α catalytic subunit (PIK3CA) gene is known to be involved in the pathogenesis of several types of human cancers through gene amplification, deletions or somatic missense mutations within the helical and catalytic domains. However, the PIK3CA gene status in BP-NETs has yet to be explored. This study aimed to investigate the PIK3CA gene status in a large series of BP-NETs by direct gene sequencing and to analyse its correlation with the main clinicopathological parameters. To the best of our knowledge, we demonstrated for the first time a high frequency of somatic missense mutations (23.2%) in the PIK3CA gene in a series of 190 BP-NETs, including 75 TCs, 23 ACs, 17 LCNECs and 75 SCLCs. The frequency of the PIK3CA gene mutation in the kinase domain was higher (17.9%) than that in the helical domain (5.3%). When the mutational status of the PIK3CA gene was compared with the main clinical and pathological characteristics of the BP-NET patients, we found a significant association between PIK3CA gene mutations and BP-NET histology (P=0.011). Interestingly, the frequency of PIK3CA gene mutations increased with the biological aggressiveness of all BP-NETs, except LCNECs. In conclusion, our results suggest that PIK3CA gene mutations may play a key role in tumourigenesis and aggressiveness of BP-NETs. The PIK3CA gene may represent a favourable candidate for an effective therapeutic strategy in the treatment of patients with BP-NETs.
登录
查看更多内容
影响因子：
158.5
作者：
Lynch, TJ;Bell, DW;Haber, DA
通讯作者：
Haber, DA
胃腺癌中PIK3CA的突变。
影响因子：
3.8
作者：
Li, VSW;Wong, CW;Chan, TL;Chan, ASW;Zhao, W;Chu, KM;So, S;Chen, X;Yuen, ST;Leung, SY
通讯作者：
Leung, SY
DOI：
10.1016/j.jamcollsurg.2009.03.006
发表时间：
2009-07-01
影响因子：
5.2
作者：
Pitt, Susan C.;Chen, Herbert;Kunnimalaiyaan, Muthusamy
通讯作者：
Kunnimalaiyaan, Muthusamy
影响因子：
56.9
作者：
Miled, Nabil;Yan, Ying;Williams, Roger L.
通讯作者：
Williams, Roger L.
影响因子：
9.7
作者：
Shibata, Tatsuhiro;Kokubu, Akiko;Hirohashi, Setsuo
通讯作者：
Hirohashi, Setsuo