PIK3CA Mutations and PTEN Loss in Salivary Duct Carcinomas
PIK3CA Mutations and PTEN Loss in Salivary Duct Carcinomas
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DOI：
10.1097/pas.0b013e3182880d5a
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发表时间：
2013-08-01
影响因子：
5.6
通讯作者：
Chiosea, Simion I.
中科院分区：
文献类型：
--
作者：
Griffith, Christopher C.;Seethala, Raja R.;Chiosea, Simion I.
摘要涎腺导管癌是一种侵袭性的恶性肿瘤，常发生于晚期。已知编码磷酸肌醇3-激酶（PIK 3CA）的p110 α催化亚基的基因的突变/扩增和/或磷酸酶和张力蛋白同源物（PTEN）的缺失激活磷酸肌醇3-激酶（PI 3 K）途径，并且可以代表治疗靶标。在7/34例（20.5%）SDC中，SNaPshot聚合酶链反应检测到PIK 3CA外显子9 [p.E545K（n = 3）和p.E542K（n = 2）]或外显子20 [p.H1047R（n = 2）]突变。在3个具有常规形态的新生SDC中鉴定出PIK 3CA p.E545K突变。唯一一例间变性转化的SDC显示PIK 3CA p.H1047R突变，而在多形性腺瘤中产生的SDC中鉴定出2个PIK 3CA p.E542K突变中的1个。通过荧光原位杂交，16个检测的SDC均未显示PIK 3CA扩增。荧光原位杂交鉴定了16个测试的SDC中的8个（50%）中的PTEN缺失[纯合缺失（n = 3），染色体10单体性（n = 3），半合子缺失（n = 2）]。两例病例同时显示PIK 3CA突变和PTEN缺失，表明这些事件并不相互排斥。这些发现为SDC患者中PI 3 K通路的治疗靶向提供了分子基础。
Salivary duct carcinoma (SDC) is an aggressive malignancy that frequently presents at an advanced stage. Mutations/amplification of the gene encoding the p110 alpha catalytic subunit of phosphoinositide 3-kinase (PIK3CA) and/or loss of the phosphatase and tensin homolog (PTEN) are known to activate the phosphoinositide 3-kinase (PI3K) pathway and may represent a therapeutic target. In 7 of 34 SDCs (20.5%) a SNaPshot polymerase chain reaction detected PIK3CA exon 9 [p.E545K (n = 3) and p.E542K (n = 2)] or exon 20 [p.H1047R (n = 2)] mutations. PIK3CA p.E545K mutation was identified in 3 de novo SDCs with conventional morphology. The only case of SDC with anaplastic transformation showed PIK3CA p.H1047R mutation, whereas 1 of 2 PIK3CA p.E542K mutations was identified in SDC arising in a pleomorphic adenoma. None of the 16 tested SDCs showed PIK3CA amplification by fluorescence in situ hybridization. Fluorescence in situ hybridization identified PTEN loss in 8 of 16 tested SDCs (50%) [homozygous deletion (n = 3), chromosome 10 monosomy (n = 3), hemizygous deletion (n = 2)]. Two cases showed both PIK3CA mutation and PTEN loss, suggesting that these events are not mutually exclusive. These findings offer a molecular rationale for therapeutic targeting of the PI3K pathway in patients with SDC.