Molecular characterization of gallbladder cancer using somatic mutation profiling.
Molecular characterization of gallbladder cancer using somatic mutation profiling.
复制标题
使用体细胞突变分析对胆囊癌的分子表征。
DOI：
10.1016/j.humpath.2013.11.001
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发表时间：
2014-04
期刊：
影响因子：
3.3
通讯作者：
Roa, Ivan
中科院分区：
文献类型：
--
作者：
Javle, Milind;Rashid, Asif;Churi, Chaitanya;Kar, Siddhartha;Zuo, Mingxin;Eterovic, Agda Karina;Nogueras-Gonzalez, Graciela M.;Janku, Filip;Shroff, Rachna T.;Aloia, Thomas A.;Vauthey, Jean-Nicholas;Curley, Steven;Mills, Gordon;Roa, Ivan
胆囊癌相对罕见，在某些地理位置发病率较高，包括拉丁美洲，东亚和南亚以及东欧。这种疾病的分子表征是有限的，晚期疾病的靶向治疗选择仍然是一个开放的研究领域。在本研究中，从切除的胆囊癌病例（n=72）中获得的手术病理检查了靶向体细胞突变的存在。所有病例均经福尔马林固定和石蜡包埋（FFPE）。采用了两种方法：a）基于质谱分析的33个通常涉及实体瘤的基因中的159个点（“热点”）突变，和B）检查182个癌症相关基因中的完整编码序列的下一代测序（NGS）平台。分析了57例热点突变和15例NGS。在9例病例中发现了14个热点突变。其中，KRAS突变与多变量分析的生存率差显著相关。其他靶向突变包括PIK 3CA（N=2）和ALK（N=1）。在NGS上，在15例病例中观察到26个突变。P53和PI 3激酶途径（STK 11、RICTOR、TSC 2）突变常见。一个病例有FGF 10扩增，而另一个有FGF 3-TACC基因融合，以前没有在胆囊癌中描述。总之，使用来自胆囊癌的档案FFPE样品进行体细胞突变谱分析是可行的。NGS尤其可能是鉴定用于靶向治疗的新突变的有用平台。
Gallbladder cancer is relatively uncommon with high incidence in certain geographic locations, including Latin America, East and South Asia and Eastern Europe. Molecular characterization of this disease has been limited and targeted therapy options for advanced disease remain an open area of investigation. In the present study, surgical pathology obtained from resected gallbladder cancer cases (n=72) was examined for the presence of targetable, somatic mutations. All cases were formalin-fixed and paraffin-embedded (FFPE). Two approaches were used: a) mass spectroscopy-based profiling for 159 point (‘hot-spot’) mutations in 33 genes commonly involved in solid tumors and b) next-generation sequencing (NGS) platform that examined the complete coding sequence of in 182 cancer-related genes. Fifty-seven cases were analyzed for hotspot mutations and 15 for NGS. Fourteen hotspot mutations were identified in nine cases. Of these, KRAS mutation was significantly associated with poor survival on multivariate analysis. Other targetable mutations included PIK3CA (N=2) and ALK (N=1). On NGS, 26 mutations were noted in 15 cases. P53 and PI3 kinase pathway (STK11, RICTOR,TSC2) mutations were common. One case had FGF10 amplification while another had FGF3-TACC gene fusion, not previously described in gallbladder cancer. In conclusion, somatic mutation profiling using archival FFPE samples from gallbladder cancer is feasible. NGS, in particular may be a useful platform for identifying novel mutations for targeted therapy.
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