Tian He, Yang Zhenlin, Yang Junhui, Chen Ying, Li Lin, Fan Tao, Liu Tiejun, Bai Guangyu, Gao Yibo, He Jie
Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
Department of Respiratory Medicine, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
J Natl Cancer Cent. 2024 Dec 4;5(1):82-92. doi: 10.1016/j.jncc.2024.12.001. eCollection 2025 Feb.
Pulmonary blastoma (PB) is a rare subtype of lung cancer. Currently, the underlying pathogenesis mechanisms of PB have not been fully illustrated, and the therapeutic approach for this entity is limited.
Whole-exome sequencing (WES), RNA sequencing, and DNA methylation profiling are applied to seven PB patients. Multi-omics data of pulmonary sarcomatoid carcinoma (PSC) and pituitary blastoma (PitB) from previous studies are invoked to illuminate the associations among PB and these malignacies.
We portray the genomic alteration spectrum of PB and find that is with the highest alteration rate (86 %). We uncover that alterations, Wnt signaling pathway dysregulation and IGF2 imprinting dysregulation are the potential pathogenesis mechanisms of PB. Moreover, we reveal that the integrated molecular features of PB are distinct from PSC, and the molecular characteristics of PB are more similar to PitB than to PSC. Pancancer analysis show that the tumor mutation burden (TMB) and leukocyte fraction (LF) of PB are low, while some cases are positive for PD-L1 or have CD8-positive focal areas, implying the potential applicability of immunotherapy in selected PB patients.
This study depicts the integrated molecular characteristics of PB and offers novel insights into the pathogenesis and therapeutic strategies of PB.
肺母细胞瘤（PB）是肺癌的一种罕见亚型。目前，PB的潜在发病机制尚未完全阐明，针对该疾病实体的治疗方法有限。
对7例PB患者进行全外显子测序（WES）、RNA测序和DNA甲基化分析。调用先前研究中肺肉瘤样癌（PSC）和垂体母细胞瘤（PitB）的多组学数据，以阐明PB与这些恶性肿瘤之间的关联。
我们描绘了PB的基因组改变谱，发现[具体基因]的改变率最高（86%）。我们发现[具体基因]改变、Wnt信号通路失调和IGF2印记失调是PB的潜在发病机制。此外，我们发现PB的综合分子特征与PSC不同，PB的分子特征与PitB更相似，而不是与PSC相似。泛癌分析表明，PB的肿瘤突变负荷（TMB）和白细胞分数（LF）较低，而一些病例的PD-L1呈阳性或有CD8阳性局灶区域，这意味着免疫疗法在部分PB患者中具有潜在的适用性。
本研究描绘了PB的综合分子特征，并为PB的发病机制和治疗策略提供了新的见解。
