PIK3CA exon9 mutations associate with reduced survival, and are highly concordant between matching primary tumors and metastases in endometrial cancer.
PIK3CA exon9 mutations associate with reduced survival, and are highly concordant between matching primary tumors and metastases in endometrial cancer.
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DOI：
10.1038/s41598-017-10717-z
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发表时间：
2017-08-31
影响因子：
4.6
通讯作者：
Hoivik EA
中科院分区：
文献类型：
--
作者：
Mjos S;Werner HMJ;Birkeland E;Holst F;Berg A;Halle MK;Tangen IL;Kusonmano K;Mauland KK;Oyan AM;Kalland KH;Lewis AE;Mills GB;Krakstad C;Trovik J;Salvesen HB;Hoivik EA
磷酸肌醇-3-激酶（PI3K）催化亚单位α基因（PIK3CA）突变在子宫内膜癌中很常见。我们对280例原发性子宫内膜癌的PIK3CA外显子9和外显子20进行了测序，分别通过基因表达和蛋白数据评估其与临床病理变量、患者生存率以及与PIK3CA mRNA和磷酸化- akt1的相关性。虽然PIK3CA突变通常对生存没有影响，并且与临床病理变量无关，但外显子9电荷改变突变（在取代的氨基酸残基上提供正电荷）的患者与较差的生存相关（p = 0.018）。此外，我们在转移性环境中对PIK3CA突变进行了表征，包括32例原发肿瘤和转移相匹配的患者，发现高度一致性（85.7%，7例患者中有6例），表明异质性有限。与原发肿瘤相比，PIK3CA mRNA水平在转移瘤中升高（p = 0.031），与PIK3CA突变状态无关，而与PIK3CA mRNA表达降低有关。PIK3CA突变的肿瘤在原发灶（p < 0.001）和转移灶（p = 0.010）中表达更高的p-AKT/AKT蛋白水平。我们的研究结果支持PI3K信号通路可能被激活的观点，既依赖于PIK3CA突变，也独立于PIK3CA突变，这是在设计子宫内膜癌中PIK3通路靶向策略时应考虑的一个方面。
Mutations of the phosphoinositide-3-kinase (PI3K) catalytic subunit alpha gene (PIK3CA) are frequent in endometrial cancer. We sequenced exon9 and exon20 of PIK3CA in 280 primary endometrial cancers to assess the relationship with clinicopathologic variables, patient survival and associations with PIK3CA mRNA and phospho-AKT1 by gene expression and protein data, respectively. While PIK3CA mutations generally had no impact on survival, and were not associated with clinicopathological variables, patients with exon9 charge-changing mutations, providing a positive charge at the substituted amino acid residue, were associated with poor survival (p = 0.018). Furthermore, we characterized PIK3CA mutations in the metastatic setting, including 32 patients with matched primary tumors and metastases, and found a high level of concordance (85.7%; 6 out of 7 patients), suggesting limited heterogeneity. PIK3CA mRNA levels were increased in metastases compared to the primary tumors (p = 0.031), independent of PIK3CA mutation status, which rather associated with reduced PIK3CA mRNA expression. PIK3CA mutated tumors expressed higher p-AKT/AKT protein levels, both within primary (p < 0.001) and metastatic lesion (p = 0.010). Our results support the notion that the PI3K signaling pathway might be activated, both dependent- and independently of PIK3CA mutations, an aspect that should be considered when designing PIK3 pathway targeting strategies in endometrial cancer.
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影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
影响因子：
64.8
作者：
通讯作者：
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DOI：
10.1073/pnas.0701005104
发表时间：
2007-03-27
影响因子：
11.1
作者：
Gymnopoulos, Marco;Elsliger, Marc-Andre;Vogt, Peter K.
通讯作者：
Vogt, Peter K.
影响因子：
30.8
作者：
Gibson WJ;Hoivik EA;Halle MK;Taylor-Weiner A;Cherniack AD;Berg A;Holst F;Zack TI;Werner HM;Staby KM;Rosenberg M;Stefansson IM;Kusonmano K;Chevalier A;Mauland KK;Trovik J;Krakstad C;Giannakis M;Hodis E;Woie K;Bjorge L;Vintermyr OK;Wala JA;Lawrence MS;Getz G;Carter SL;Beroukhim R;Salvesen HB
通讯作者：
Salvesen HB
影响因子：
11.5
作者：
Hayes, Monica Prasad;Wang, Hong;Ellenson, Lora Hedrick
通讯作者：
Ellenson, Lora Hedrick