转移性肾上腺皮质癌的突变率和肿瘤异质性高于原发性肿瘤。
Metastatic adrenocortical carcinoma displays higher mutation rate and tumor heterogeneity than primary tumors.
机构信息
Endocrine Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
Center for Cancer Research, Collaborative Bioinformatics Resource, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
出版信息
Nat Commun. 2018 Oct 9;9(1):4172. doi: 10.1038/s41467-018-06366-z.
Adrenocortical cancer (ACC) is a rare cancer with poor prognosis and high mortality due to metastatic disease. All reported genetic alterations have been in primary ACC, and it is unknown if there is molecular heterogeneity in ACC. Here, we report the genetic changes associated with metastatic ACC compared to primary ACCs and tumor heterogeneity. We performed whole-exome sequencing of 33 metastatic tumors. The overall mutation rate (per megabase) in metastatic tumors was 2.8-fold higher than primary ACC tumor samples. We found tumor heterogeneity among different metastatic sites in ACC and discovered recurrent mutations in several novel genes. We observed 37-57% overlap in genes that are mutated among different metastatic sites within the same patient. We also identified new therapeutic targets in recurrent and metastatic ACC not previously described in primary ACCs.
肾上腺皮质癌（ACC）是一种罕见的癌症，由于转移性疾病，预后不良，死亡率高。所有报道的遗传改变都发生在原发性 ACC 中，目前尚不清楚 ACC 是否存在分子异质性。在这里，我们报告了与原发性 ACC 相比，转移性 ACC 相关的遗传变化以及肿瘤异质性。我们对 33 个转移性肿瘤进行了全外显子组测序。转移性肿瘤的总体突变率（每百万碱基）是原发性 ACC 肿瘤样本的 2.8 倍。我们发现 ACC 不同转移部位之间存在肿瘤异质性，并在几个新基因中发现了复发性突变。我们观察到同一患者不同转移部位的基因突变有 37-57%的重叠。我们还在以前未在原发性 ACC 中描述的复发性和转移性 ACC 中确定了新的治疗靶点。
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