Rare Mutations in the PIK3CA Gene Contribute to Aggressive Endometrial Cancer
Rare Mutations in the PIK3CA Gene Contribute to Aggressive Endometrial Cancer
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DOI：
10.1089/dna.2009.0939
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发表时间：
2010-02-01
影响因子：
3.1
通讯作者：
Mitev, Vanio
中科院分区：
文献类型：
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作者：
Konstantinova, Darina;Kaneva, Radka;Mitev, Vanio
子宫内膜癌（EC）是一种常见的妇科恶性肿瘤，其分子基础通常包括PIK 3CA和KRAS基因的突变激活。我们的目的是根据患者的临床病理学特征确定这两个基因的突变分布。我们在108个连续的EC肿瘤样本中对KRAS基因的外显子1和PIK 3CA基因的外显子9和20进行测序。108例病例中有24例（22.2%）存在PIK 3CA突变，108例病例中有18例（16.7%）存在KRAS突变。PIK 3CA突变在KRAS突变的样品中更频繁地发生（7/18，38.9%; p = 0.06）（17/90，18.9%），在转移性肿瘤中的发生率极高（4/9，44.4%; p = 0.1）和显示浆液性分化的样本-浆液性和混合性浆液性/浆液性肿瘤（6/12，50.0%; p = 0.021）-其中KRAS突变罕见（分别为11.1%和16.7%），并且不独立于PIK 3CA突变而存在。非热点（即，在转移性病例中，PIK 3CA基因中的非E542 K、-E545 K和-H1047 R突变显示出更高的频率（3/9，33.3%; p = 0.05）。显示浆液性分化的肿瘤显示出特定的模式-它们仅在PIK 3CA外显子20中具有突变（5/12，41.7%; p = 0.005），并且其中大多数是非热点（4/12，33.3%; p = 0.02）。在所有其他比较中，外显子9和20突变分布没有差异。这些结果表明，需要进一步探索PIK 3CA突变在侵袭性EC方面的意义。
The molecular basis of endometrial cancer (EC), a common gynecologic malignancy, often includes mutational activation of the PIK3CA and KRAS genes. We aimed to determine the distribution of mutations in the two genes depending on patient clinocopathological characteristics. We sequenced exon 1 of the KRAS gene and exons 9 and 20 of the PIK3CA gene in 108 consecutive EC tumor samples. PIK3CA mutations were present in 24 of the 108 (22.2%) cases and KRAS mutations in 18 of the 108 (16.7%) cases. PIK3CA mutations occurred more frequently in KRAS-mutated samples (7/18, 38.9%; p = 0.06) than in KRAS wild type (17/90, 18.9%) and showed a very high frequency in metastatic tumors (4/9, 44.4%; p = 0.1) and in samples displaying serous differentiation-serous and mixed endometrioid/serous tumors (6/12, 50.0%; p = 0.021)-where KRAS mutations were rare (11.1% and 16.7%, respectively) and did not exist independently of a PIK3CA mutation. Non-hotspot (i.e., non-E542K, -E545K, and -H1047R) mutations in the PIK3CA gene showed higher frequency in metastatic cases (3/9, 33.3%; p = 0.05). Tumors displaying serous differentiation showed a particular pattern-they harbored exclusively mutations in PIK3CA exon 20 (5/12, 41.7%; p = 0.005) and most of these were non-hotspot (4/12, 33.3%; p = 0.02). In all other comparisons exons 9 and 20 mutation distribution did not differ. These results suggest the need for further exploration of the significance of PIK3CA mutations in respect to aggressive EC.