Lawson Nora M, Ye Lingqun, Cho Chae Yun, Zhao Bo, Mitchell Thomas, Martín-Barrio Inés, Beernaert Bruno, Gupta Archit, Banu Matei, Lissanu Yonathan, Shaffer Sydney, Tawbi Hussein, Li Jing, Gule-Monroe Maria Kristine, Alvarez-Breckenridge Christopher A, Huse Jason T, Murphy Mariella Blum, Yin Feng, Lang Frederick F, Parkes Eileen E, Weinberg Jeffrey S, Akdemir Kadir C
Department of Neurosurgery, MD Anderson Cancer Center, Houston, TX, USA.
Department of Genetics, MD Anderson Cancer Center, Houston, TX, USA.
medRxiv. 2025 Feb 26:2025.02.19.25322558. doi: 10.1101/2025.02.19.25322558.
Brain metastases in esophageal adenocarcinoma (EAC) patients are associated with poor prognosis and remain understudied. We performed multi-omics analysis with whole-genome sequencing and single-cell spatial transcriptomics on the brain metastases and matched primary tumors. Our analysis identified as a recurrent oncogene in EAC brain metastases, with 9 out of 10 cases harboring amplifications. Single-cell whole-genome and multi-region sequencing revealed that alterations, occur early during disease progression and are associated with monoclonal seeding. Although the median survival in our cohort was 13 months, one patient on HER2 antibody-drug conjugate therapy remains a long-term survivor beyond 34 months. Interestingly, the sole patient without an alteration had deletion, high T cell infiltration in the brain lesion, and survived 35 months after immune checkpoint therapy. Our findings have significant clinical implications for the treatment and management of EAC brain metastases.
食管腺癌（EAC）患者的脑转移与预后不良相关，且仍未得到充分研究。我们对脑转移灶及配对的原发性肿瘤进行了全基因组测序和单细胞空间转录组学的多组学分析。我们的分析确定 为EAC脑转移中一个反复出现的致癌基因，10例中有9例存在扩增。单细胞全基因组和多区域测序显示， 改变发生在疾病进展的早期，并与单克隆播种有关。尽管我们队列中的中位生存期为13个月，但一名接受HER2抗体药物偶联物治疗的患者在34个月后仍然是长期幸存者。有趣的是，唯一没有 改变的患者存在 缺失，脑病变中有高T细胞浸润，并且在免疫检查点治疗后存活了35个月。我们的研究结果对EAC脑转移的治疗和管理具有重要的临床意义。
