Genomic landscape and tumor mutation burden analysis of Chinese patients with sarcomatoid carcinoma of the head and neck
Genomic landscape and tumor mutation burden analysis of Chinese patients with sarcomatoid carcinoma of the head and neck
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DOI：
10.1016/j.oraloncology.2021.105436
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发表时间：
2021-08-06
期刊：
影响因子：
4.8
通讯作者：
Chen, Xi
中科院分区：
文献类型：
--
作者：
Chen, Hai-Bing;Gong, Xiao-Yang;Chen, Xi
背景：头颈部肉瘤样癌（HN）是一种罕见疾病，同时具有肉瘤样和癌性成分。肿瘤发生的遗传背景和机制在很大程度上仍未被揭示，精准治疗的进展受到限制。方法：通过 539 个泛癌基因组对 12 名 HN SC 患者进行基于 DNA 的靶向下一代测序 (NGS)，以鉴定其基因改变并研究用于精准治疗的临床可行突变。结果：TP53 被确定为最常见的突变基因。研究发现，HN SC 患者中与细胞周期、染色质重塑和组蛋白修饰相关的基因经常发生突变。六名患者的受体酪氨酸激酶（RTK）也发生了变化。此外，四名患者的下游 RAS 和 PI3 激酶通路成员发生突变，PIK3CA 被确定为该通路中最常见的突变基因。肿瘤突变负荷（TMB）值范围为每兆碱基 0.71 至 14.71，中位数为 4.34。 PIK3CA突变患者的TMB值显着高于PIK3CA野生型患者。结论：这是第一项专门调查中国 HN SC 患者基因组改变的研究。我们的研究结果表明，12名患者中有10名可以与目前临床实践或活跃临床试验中可用的靶向治疗或免疫治疗相匹配，这表明精准治疗具有改善罕见病患者长期预后的潜在效用。由于本研究的患者数量较少，因此需要在更大的队列中验证研究结果。
Background: Sarcomatoid carcinoma (SC) of the head and neck (HN) is a rare disease that has both sarcomatoid and cancerous components. The genetic background and mechanisms of tumorigenesis remain largely unrevealed, and the progress of precision therapy has been limited. Methods: Targeted DNA-based next-generation sequencing (NGS) was performed by a 539 genes panel of pancancer in 12 patients with SC of the HN to identify their genetic alterations and investigate clinically actionable mutations for use in precision treatment. Results: TP53 was identified as the most frequently mutated gene. Genes related to the cell cycling, chromatin remodeling and histone modification were found to be frequently mutated in patients with SC of the HN. Alterations in receptor tyrosine kinases (RTKs) were also found in six patients. In addition, four patients had mutations in members of the downstream RAS and PI3-kinase pathways, PIK3CA was identified as the most frequently mutated gene in this pathway. The tumor mutation burden (TMB) value ranged from 0.71 to 14.71 per megabase, with a median of 4.34. The TMB value of PIK3CA mutation patients was significantly higher than that of PIK3CA wild-type patients. Conclusions: This was the first study to investigate genomic alterations specifically in Chinese patients with SC of the HN. Our research results showed that 10 out of 12 patients can match the targeted therapies or immunotherapy currently available in clinical practice or active clinical trials, suggesting precision therapy has the potential utility to improve the long-term prognosis for patients with the rare disease. Due to the small number of patients in this study, the findings need to be validated in a larger cohort.