Clinical and molecular characterization of HER2 amplified-pancreatic cancer
Clinical and molecular characterization of HER2 amplified-pancreatic cancer
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DOI：
10.1186/gm482
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发表时间：
2013-08-31
期刊：
影响因子：
12.3
通讯作者：
Biankin, Andrew V.
中科院分区：
文献类型：
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作者：
Chou, Angela;Waddell, Nicola;Biankin, Andrew V.
背景：胰腺癌是最致命的和分子多样性的恶性肿瘤之一。在不同疾病类型中靶向特定分子机制的治疗方法的再利用为快速改善结果提供了潜力。虽然HER2扩增发生在胰腺癌，它是不充分的特点，以利用抗HER2 therapy.Methods的潜力：HER2扩增检测和进一步分析，使用多种基因组测序方法。标准化的参考实验室测定定义了一个大的胰腺导管腺癌（PDAC）患者队列（n = 469）中的HER2扩增。结果：在PDAC患者的HER2基因座上发现了扩增的倒位事件（1 MB）。使用标准化的实验室检测，我们建立了PDAC中HER2扩增的诊断标准，并观察到2%的患病率。在临床上，HER2扩增的PDAC的特征在于缺乏肝转移，以及肺和脑转移的优势。不包括乳腺癌和胃癌，HER2扩增的癌症在美国的发病率是> 22，000每年。结论：HER2扩增发生在2%的PDAC中，并且具有对临床实践有意义的独特特征。PDAC的分子异质性意味着即使发生率为2%，也是抗HER2治疗的有吸引力的靶点，因为PDAC的选择有限。基于HER2扩增而不是器官来源招募患者，可以使抗HER2疗法在不太常见的癌症类型中可行。
Background: Pancreatic cancer is one of the most lethal and molecularly diverse malignancies. Repurposing of therapeutics that target specific molecular mechanisms in different disease types offers potential for rapid improvements in outcome. Although HER2 amplification occurs in pancreatic cancer, it is inadequately characterized to exploit the potential of anti-HER2 therapies.Methods: HER2 amplification was detected and further analyzed using multiple genomic sequencing approaches. Standardized reference laboratory assays defined HER2 amplification in a large cohort of patients (n = 469) with pancreatic ductal adenocarcinoma (PDAC).Results: An amplified inversion event (1 MB) was identified at the HER2 locus in a patient with PDAC. Using standardized laboratory assays, we established diagnostic criteria for HER2 amplification in PDAC, and observed a prevalence of 2%. Clinically, HER2-amplified PDAC was characterized by a lack of liver metastases, and a preponderance of lung and brain metastases. Excluding breast and gastric cancer, the incidence of HER2-amplified cancers in the USA is >22,000 per annum.Conclusions: HER2 amplification occurs in 2% of PDAC, and has distinct features with implications for clinical practice. The molecular heterogeneity of PDAC implies that even an incidence of 2% represents an attractive target for anti-HER2 therapies, as options for PDAC are limited. Recruiting patients based on HER2 amplification, rather than organ of origin, could make trials of anti-HER2 therapies feasible in less common cancer types.