Association between histone lysine methyltransferase KMT2C mutation and clinicopathological factors in breast cancer
Association between histone lysine methyltransferase KMT2C mutation and clinicopathological factors in breast cancer
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组蛋白赖氨酸甲基转移酶KMT2C突变与乳腺癌临床病理因素的关系
DOI：
10.1016/j.biopha.2019.108997
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发表时间：
2019-08-01
影响因子：
7.5
通讯作者：
Liao, Ning
中科院分区：
文献类型：
--
作者：
Chen, Xiaoqing;Zhang, Guochun;Liao, Ning
组蛋白赖氨酸甲基转移酶2C（KMT 2C）作为表观遗传学的重要调控因子，在多种人类癌症中频繁发生突变，被认为与多种癌症的发生和发展至关重要。然而，KMT 2C突变与乳腺癌患者临床病理特征之间的关系尚不清楚。在本研究中，我们进行了新一代测序，以调查广东省人民医院（GDPH）411例未经治疗的中国乳腺癌患者的KMT 2C突变状态，并将结果与癌症基因组图谱中的乳腺癌患者的结果进行了比较（TCGA，n = 981）和乳腺癌国际联盟分子分类学（METABRIC，n = 1454）队列。GDPH队列的KMT 2C突变率为8.0%（33/411），而TCGA和METABRIC队列分别为7.0%（69/981）和14.5%（211/1454）。在GDPH队列中观察到19个新突变。发现KMT 2C突变与50岁以上的患者显著相关（GDPH：p = 0.007; TCGA：p = 0.005; METABRIC：p = 0.015）。HR + /HER 2-乳腺癌患者的KMT 2C突变率高于其他亚型（GDPH：p = 0.047; TCGA：p = 0.032; METABRIC：p = 0.046）。此外，在浸润性小叶乳腺癌（ILC）中观察到GDPH队列中的KMT 2C突变为30.8%（4/13）。此外，未发现KMT 2C突变是乳腺癌患者预后的独立风险因素[TCGA：风险比（HR），1.71; 95%置信区间（CI），0.88-3.31; p = 0.111; METABRIC：HR，2.03; 95% CI，0.45-3.08; p = 0.419]。这是首次初步阐明KMT 2C突变在中国乳腺癌患者中的作用，并进一步确定了KMT 2C突变在人种和种族之间的显著差异。KMT 2C可能是中国ILC患者的易感基因，这将有助于定义可以从适应性、个性化筛查策略中受益的高危人群。
As an important regulator of epigenetics, histone lysine methyltransferase 2C (KMT2C), is frequently mutated in multiple human cancers and is considered to be crucial for the occurrence and development of numerous cancers. However, the relationship between KMT2C mutation and clinicopathological characteristics in patients with breast cancer is unclear. In the present study, we performed next-generation sequencing to investigate the mutation status of KMT2C in 411 treatment-naive Chinese patients with breast cancer at Guangdong Provincial People's Hospital (GDPH), and further compared the results to those of patients with breast cancer from The Cancer Genome Atlas (TCGA, n = 981) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC, n = 1454) cohorts. The KMT2C mutation rate was 8.0% (33/411) in the GDPH cohort, whereas that in the TCGA and the METABRIC cohorts was 7.0% (69/981) and 14.5% (211/1454), respectively. Nineteen novel mutations were observed in the GDPH cohort. KMT2C mutations were found to be significantly associated with patients older than 50 years (GDPH: p = 0.007; TCGA: p = 0.005; METABRIC: p = 0.015). The KMT2C mutation rate in HR + /HER2- breast cancer patients was higher than that in the other subtypes (GDPH: p = 0.047; TCGA: p = 0.032; METABRIC: p = 0.046). In addition, KMT2C mutations in the GDPH cohort were observed in invasive lobular breast cancer (ILC) at 30.8% (4/13). Further, KMT2C mutation was not found to be an independent risk factor in the prognosis of patients with breast cancer [TCGA: hazard ratio (HR), 1.71; 95% confidence interval (CI), 0.88-3.31; p = 0.111; METABRIC: HR, 2.03; 95% CI, 0.45-3.08; p = 0.419]. This is the first study to preliminarily elucidate the role of KMT2C mutations in Chinese patients with breast cancer and further identified significant KMT2C mutation differences according to race and ethnicity. KMT2C might be a susceptibility gene of Chinese patients with ILC that would help define high-risk groups that could benefit from adapted, personalized screening strategies.