PIK3CA and PTEN Gene and Exon Mutation-Specific Clinicopathologic and Molecular Associations in Colorectal Cancer
PIK3CA and PTEN Gene and Exon Mutation-Specific Clinicopathologic and Molecular Associations in Colorectal Cancer
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DOI：
10.1158/1078-0432.ccr-12-3614
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发表时间：
2013-06-15
影响因子：
11.5
通讯作者：
Sieber, Oliver M.
中科院分区：
文献类型：
--
作者：
Day, Fiona L.;Jorissen, Robert N.;Sieber, Oliver M.
目的：PIK 3CA和PTEN突变在结直肠癌中普遍存在，并且是对丝裂原活化蛋白/细胞外信号调节激酶抑制剂和抗EGF受体抗体治疗的应答的潜在标志物。磷脂酰肌醇3-激酶（PI 3 K）通路突变，临床病理特征，分子特征和预后之间的关系仍然存在争议。实验设计：共筛选了1,093例I-IV期结直肠癌的PIK 3CA（外显子9和20），KRAS（密码子12-13），BRAF（密码子600）突变和微卫星不稳定性（MSI）。对744例和489例患者进行了PTEN（外显子3-8）和CpG岛甲基化表型（CIMP）检测。结果：PIK 3CA和PTEN基因突变在结直肠癌中的检出率分别为11.9%和5.8%。PTEN突变与近端肿瘤、粘液组织学、MSI-高（MSI-H）、CIMP-高（CIMP-H）和BRAF突变相关（P < 0.02）。PIK 3CA突变与年龄、近端肿瘤、粘液组织学和KRAS突变相关（P < 0.04）。在综合队列分析中，PIK 3CA外显子9和20突变在近端癌、CIMP-L和KRAS突变癌中的比例过高（P
Purpose: PIK3CA and PTEN mutations are prevalent in colorectal cancer and potential markers of response to mitogen-activated protein/extracellular signal-regulated kinase inhibitors and anti-EGF receptor antibody therapy. Relationships between phosphoinositide 3-kinase (PI3K) pathway mutation, clinicopathologic characteristics, molecular features, and prognosis remain controversial.Experimental Design: A total of 1,093 stage I-IV colorectal cancers were screened for PIK3CA (exons 9 and 20), KRAS (codons 12-13), BRAF (codon 600) mutations, and microsatellite instability (MSI). PTEN (exons 3-8) and CpG island methylator phenotype (CIMP) status were determined in 744 and 489 cases. PIK3CA data were integrated with 17 previous reports (n = 5,594).Results: PIK3CA and PTEN mutations were identified in 11.9% and 5.8% of colorectal cancers. PTEN mutation was associated with proximal tumors, mucinous histology, MSI-high (MSI-H), CIMP-high (CIMP-H), and BRAF mutation (P < 0.02). PIK3CA mutation was related to older age, proximal tumors, mucinous histology, and KRAS mutation (P < 0.04). In integrated cohort analysis, PIK3CA exon 9 and 20 mutations were overrepresented in proximal, CIMP-low (CIMP-L), and KRAS-mutated cancers (P