Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Cancer Cell. 2018 Sep 10;34(3):427-438.e6. doi: 10.1016/j.ccell.2018.08.008.
We integrated the genomic sequencing of 1,918 breast cancers, including 1,501 hormone receptor-positive tumors, with detailed clinical information and treatment outcomes. In 692 tumors previously exposed to hormonal therapy, we identified an increased number of alterations in genes involved in the mitogen-activated protein kinase (MAPK) pathway and in the estrogen receptor transcriptional machinery. Activating ERBB2 mutations and NF1 loss-of-function mutations were more than twice as common in endocrine resistant tumors. Alterations in other MAPK pathway genes (EGFR, KRAS, among others) and estrogen receptor transcriptional regulators (MYC, CTCF, FOXA1, and TBX3) were also enriched. Altogether, these alterations were present in 22% of tumors, mutually exclusive with ESR1 mutations, and associated with a shorter duration of response to subsequent hormonal therapies.
我们整合了 1918 例乳腺癌的基因组测序数据，包括 1501 例激素受体阳性肿瘤，并结合了详细的临床信息和治疗结果。在 692 例先前接受过激素治疗的肿瘤中，我们发现参与丝裂原活化蛋白激酶（MAPK）途径和雌激素受体转录机制的基因发生了更多的改变。在内分泌抵抗性肿瘤中，ERBB2 激活突变和 NF1 失活突变的发生率是前者的两倍多。其他 MAPK 途径基因（EGFR、KRAS 等）和雌激素受体转录调节剂（MYC、CTCF、FOXA1 和 TBX3）的改变也很丰富。总的来说，这些改变存在于 22%的肿瘤中，与 ESR1 突变互斥，并且与随后激素治疗的反应持续时间较短相关。
