npj Breast Cancer ( IF 5.9 ) Pub Date : 2021-06-01 , DOI: 10.1038/s41523-021-00278-w Rui Luo 1 , Weelic Chong 1 , Qiang Wei 2 , Zhenchao Zhang 1 , Chun Wang 1 , Zhong Ye 1 , Maysa M Abu-Khalaf 1 , Daniel P Silver 1 , Robert T Stapp 3 , Wei Jiang 3 , Ronald E Myers 1 , Bingshan Li 2 , Massimo Cristofanilli 4 , Hushan Yang 1
Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer. Although it is a rare subtype, IBC is responsible for roughly 10% of breast cancer deaths. In order to obtain a better understanding of the genomic landscape and intratumor heterogeneity (ITH) in IBC, we conducted whole-exome sequencing of 16 tissue samples (12 tumor and four normal samples) from six hormone-receptor-positive IBC patients, analyzed somatic mutations and copy number aberrations, and inferred subclonal structures to demonstrate ITH. Our results showed that KMT2C was the most frequently mutated gene (42%, 5/12 samples), followed by HECTD1, LAMA3, FLG2, UGT2B4, STK33, BRCA2, ACP4, PIK3CA, and DNAH8 (all nine genes tied at 33% frequency, 4/12 samples). Our data indicated that PTEN and FBXW7 mutations may be considered driver gene mutations for IBC. We identified various subclonal structures and different levels of ITH between IBC patients, and mutations in the genes EIF4G3, IL12RB2, and PDE4B may potentially generate ITH in IBC.
中文翻译:
全外显子组测序鉴定炎症性乳腺癌的体细胞突变和瘤内异质性
炎症性乳腺癌 (IBC) 是最具侵袭性的乳腺癌形式。尽管它是一种罕见的亚型,但 IBC 导致大约 10% 的乳腺癌死亡。为了更好地了解 IBC 中的基因组景观和肿瘤内异质性 (ITH),我们对来自 6 名激素受体阳性 IBC 患者的 16 个组织样本(12 个肿瘤和 4 个正常样本)进行了全外显子组测序,分析了体细胞突变和拷贝数畸变,并推断亚克隆结构以证明 ITH。我们的结果显示,KMT2C是最常见的突变基因(42%,5/12 个样本),其次是HECTD1、LAMA3、FLG2、UGT2B4、STK33、BRCA2、ACP4、PIK3CA和DNAH8(所有九个基因以 33% 的频率绑定,4/12 个样本)。我们的数据表明PTEN和FBXW7突变可能被认为是 IBC 的驱动基因突变。我们确定了 IBC 患者之间的各种亚克隆结构和不同水平的 ITH,基因EIF4G3、IL12RB2和PDE4B的突变可能在 IBC 中产生 ITH。