Genetic alterations in Japanese extrahepatic biliary tract cancer.
Genetic alterations in Japanese extrahepatic biliary tract cancer.
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DOI：
10.3892/ol.2017.6224
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发表时间：
2017-07
期刊：
影响因子：
2.9
通讯作者：
Rei Noguchi;K. Yamaguchi;T. Ikenoue;Yumi Terakado;Y. Ohta;N. Yamashita;O. Kainuma;S. Yokoi;Yoshiaki Maru;H. Nagase;Y. Furukawa
中科院分区：
文献类型：
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作者：
Rei Noguchi;K. Yamaguchi;T. Ikenoue;Yumi Terakado;Y. Ohta;N. Yamashita;O. Kainuma;S. Yokoi;Yoshiaki Maru;H. Nagase;Y. Furukawa
胆道癌（BTC）是世界范围内最具破坏性的恶性肿瘤之一。然而，BTC的发展和进展的机制仍然没有得到解决。BTC包括肝外胆管癌（EBDC）、胆囊癌（GBC）和乏特壶腹癌（AVC），根据肿瘤的位置而命名。虽然肝内胆管细胞癌的遗传学改变已被研究，但EBDC，GBC和AVC的遗传学改变尚未完全了解。本研究分析了27个日本BTC细胞中50个癌症相关基因的体细胞突变，包括：11个EBDC，14个GBC和2个AVC。使用Ion AmpliSeq Cancer Panel的下一代测序在14个癌症相关基因中鉴定了总共44个体细胞突变。在44个突变中，42个被判定为病理性突变。在肿瘤蛋白53（TP 53）（14/27）、SMAD家族成员4（SMAD 4）（6/27）、磷脂酰肌醇-4，5-二磷酸3-激酶催化亚基α（PIK 3CA）（6/27）和Kirsten大鼠肉瘤（KRAS）（6/27）中发现了频繁突变; EBDC和GBC组织之间未发现显著差异。值得注意的是，PIK 3CA突变的频率高于以前的报告。这一结果可能表明，PIK 3CA-蛋白激酶B信号通路的激活，以及p53、SMAD 4和RAS丝裂原活化蛋白激酶的废除可能在日本BTC的致癌作用中具有至关重要的作用。这些发现可能有助于BTC个性化治疗的发展。
Biliary tract cancer (BTC) is one of the most devastating types of malignant neoplasms worldwide. However, the mechanisms underlying the development and progression of BTC remain unresolved. BTC includes extrahepatic bile duct carcinoma (EBDC), gallbladder carcinoma (GBC) and ampulla of Vater carcinoma (AVC), named according to the location of the tumor. Although genetic alterations of intrahepatic cholangiocarcinoma have been investigated, those of EBDC, GBC and AVC have not yet been fully understood. The present study analyzed somatic mutations of 50 cancer-associated genes in 27 Japanese BTC cells, including: 11 EBDC, 14 GBC and 2 AVC. Next-generation sequencing using an Ion AmpliSeq Cancer Panel identified a total of 44 somatic mutations across 14 cancer-associated genes. Among the 44 mutations, 42 were judged as pathological mutations. Frequent mutations were identified in tumor protein 53 (TP53) (14/27), SMAD family member 4 (SMAD4) (6/27), phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit α (PIK3CA) (6/27), and Kirsten rat sarcoma (KRAS) (6/27); no significant differences were identified between EBDC and GBC tissues. Notably, the frequency of the PIK3CA mutation was higher when compared with previous reports. This result may suggest that the activation of the PIK3CA-protein kinase B signaling pathway, in addition to the abrogation of p53, SMAD4 and RAS mitogen-activated protein kinase may have a crucial role in the carcinogenesis of Japanese BTC. These findings may be useful for the development of personalized therapies for BTC.