PIK3CA activating mutation in colorectal carcinoma: associations with molecular features and survival.
PIK3CA activating mutation in colorectal carcinoma: associations with molecular features and survival.
复制标题
DOI：
10.1371/journal.pone.0065479
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Buchanan DD
中科院分区：
文献类型：
--
作者：
Rosty C;Young JP;Walsh MD;Clendenning M;Sanderson K;Walters RJ;Parry S;Jenkins MA;Win AK;Southey MC;Hopper JL;Giles GG;Williamson EJ;English DR;Buchanan DD
10%至15%的结直肠癌中存在PIK 3CA突变。我们的目的是研究PIK3CA突变如何与结直肠癌中的其他分子改变、病理表型和生存率相关。使用直接测序对来自墨尔本协作队列研究的757个偶发肿瘤进行PIK3CA突变测试。采用免疫组化和甲基化技术评估O-6-甲基鸟嘌呤-DNA甲基转移酶（MGMT）的状态。微卫星不稳定性、CpG岛表型（CIMP）、KRAS和BRAF V600E突变状态以及病理学回顾特征均来自既往报告。在757例癌中的105例（14%）中观察到PIK3CA突变，其特征在于位于近端结肠（54% vs. 34%; P <0.001）和KRAS突变频率增加（48% vs. 25%; P <0.001）。与PIK3CA野生型肿瘤相比，在PIK3CA突变肿瘤中更常见高水平的CIMP（22% vs. 11%; P = 0.004）。 BRAF V600 E突变的发生率在这两个肿瘤组之间没有差异。PIK3CA突变的肿瘤与MGMT表达的丧失（35%对20%; P = 0.001）和肿瘤粘液分化的存在（54%对32%; P <0.001）相关。 在患有野生型BRAF肿瘤的患者中，PIK3CA突变与较差的存活率相关（HR 1.51 95%CI 1.04 - 2.19，P = 0.03）。 总之，PIK3CA突变的结直肠癌更可能在近端结肠中发展，以证明高水平的CIMP、KRAS突变和MGMT表达的丧失。PIK3CA突变也导致野生型BRAF肿瘤患者的生存率显著降低。
Mutations in PIK3CA are present in 10 to 15% of colorectal carcinomas. We aimed to examine how PIK3CA mutations relate to other molecular alterations in colorectal carcinoma, to pathologic phenotype and survival. PIK3CA mutation testing was carried out using direct sequencing on 757 incident tumors from the Melbourne Collaborative Cohort Study. The status of O-6-methylguanine-DNA methyltransferase (MGMT) was assessed using both immunohistochemistry and methyLight techniques. Microsatellite instability, CpG island phenotype (CIMP), KRAS and BRAF V600E mutation status, and pathology review features were derived from previous reports. PIK3CA mutation was observed in 105 of 757 (14%) of carcinomas, characterized by location in the proximal colon (54% vs. 34%; P<0.001) and an increased frequency of KRAS mutation (48% vs. 25%; P<0.001). High-levels of CIMP were more frequently found in PIK3CA-mutated tumors compared with PIK3CA wild-type tumors (22% vs. 11%; P = 0.004). There was no difference in the prevalence of BRAF V600E mutation between these two tumor groups. PIK3CA-mutated tumors were associated with loss of MGMT expression (35% vs. 20%; P = 0.001) and the presence of tumor mucinous differentiation (54% vs. 32%; P<0.001). In patients with wild-type BRAF tumors, PIK3CA mutation was associated with poor survival (HR 1.51 95% CI 1.04–2.19, P = 0.03). In summary, PIK3CA-mutated colorectal carcinomas are more likely to develop in the proximal colon, to demonstrate high levels of CIMP, KRAS mutation and loss of MGMT expression. PIK3CA mutation also contributes to significantly decreased survival for patients with wild-type BRAF tumors.
登录
查看更多内容
影响因子：
3.7
作者：
Garrido-Laguna I;Hong DS;Janku F;Nguyen LM;Falchook GS;Fu S;Wheler JJ;Luthra R;Naing A;Wang X;Kurzrock R
通讯作者：
Kurzrock R
影响因子：
5
作者：
Hsieh, Li-Ling;Er, Tze-Kiong;Liu, Ta-Chih
通讯作者：
Liu, Ta-Chih
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：
2.8
作者：
Herreros-Villanueva, Marta;Gomez-Manero, Noemi;Jesus Coma del Corral, Maria
通讯作者：
Jesus Coma del Corral, Maria
用PI3K/AKT/MTOR轴抑制剂治疗的晚期癌症患者的PIK3CA突变。
影响因子：
5.7
作者：
Janku F;Tsimberidou AM;Garrido-Laguna I;Wang X;Luthra R;Hong DS;Naing A;Falchook GS;Moroney JW;Piha-Paul SA;Wheler JJ;Moulder SL;Fu S;Kurzrock R
通讯作者：
Kurzrock R