黏液性乳腺癌的基因组特征
The Genomic Landscape of Mucinous Breast Cancer.
机构信息
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY.
Institute of Pathology, University Hospital Basel, Basel, Switzerland.
出版信息
J Natl Cancer Inst. 2019 Jul 1;111(7):737-741. doi: 10.1093/jnci/djy216.
Mucinous carcinoma of the breast (MCB) is a rare histologic form of estrogen receptor (ER)-positive/HER2-negative breast cancer (BC) characterized by tumor cells floating in lakes of mucin. We assessed the genomic landscape of 32 MCBs by whole-exome sequencing and/or RNA-sequencing. GATA3 (23.8%), KMT2C (19.0%), and MAP3K1 (14.3%) were the most frequently mutated genes in pure MCBs. In addition, two recurrent but not pathognomonic fusion genes, OAZ1-CSNK1G2 and RFC4-LPP, were detected in 3/31 (9.7%) and 2/31 (6.5%) samples, respectively. Compared with ER-positive/HER2-negative common forms of BC, MCBs displayed lower PIK3CA and TP53 mutation rates and fewer concurrent 1q gains and 16q losses. Clonal decomposition analysis of the mucinous and ductal components independently microdissected from five mixed MCBs revealed that they are clonally related and evolve following clonal selection or parallel evolution. Our findings indicate that MCB represents a genetically distinct ER-positive/HER2-negative form of BC.
乳腺黏液癌（MCB）是一种罕见的组织学类型，雌激素受体（ER）阳性/HER2 阴性乳腺癌（BC），其特征是肿瘤细胞漂浮在黏液湖中。我们通过全外显子组测序和/或 RNA 测序评估了 32 例 MCB 的基因组图谱。在纯 MCB 中，GATA3（23.8%）、KMT2C（19.0%）和 MAP3K1（14.3%）是最常突变的基因。此外，在 31 例（9.7%）和 2 例（6.5%）样本中分别检测到两个反复出现但非特征性融合基因 OAZ1-CSNK1G2 和 RFC4-LPP。与 ER 阳性/HER2 阴性常见 BC 形式相比，MCB 显示出较低的 PIK3CA 和 TP53 突变率，较少的 1q 增益和 16q 缺失。从 5 例混合 MCB 中独立显微解剖的黏液和导管成分的克隆分解分析表明，它们在克隆上是相关的，并遵循克隆选择或平行进化的方式进化。我们的研究结果表明，MCB 代表一种在遗传上不同的 ER 阳性/HER2 阴性 BC 形式。
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