Clinical Medical Research Center, Inner Mongolian People's Hospital, Hohhot, Inner Mongolia, China.
Inner Mongolia Key Laboratory of Gene Regulation of the Metabolic Disease, Inner Mongolian People's Hospital, Hohhot, Inner Mongolia, China.
Genes Chromosomes Cancer. 2024 Jul;63(7):e23258. doi: 10.1002/gcc.23258.
Lung cancer is the leading cause of cancer-related deaths globally. Gene fusion, a key driver of tumorigenesis, has led to the identification of numerous driver gene fusions for lung cancer diagnosis and treatment. However, previous studies focused on Western populations, leaving the possibility of unrecognized lung cancer-associated gene fusions specific to Inner Mongolia due to its unique genetic background and dietary habits. To address this, we conducted DNA sequencing analysis on tumor and adjacent nontumor tissues from 1200 individuals with lung cancer in Inner Mongolia. Our analysis established a comprehensive fusion gene landscape specific to lung cancer in Inner Mongolia, shedding light on potential region-specific molecular mechanisms underlying the disease. Compared to Western cohorts, we observed a higher occurrence of ALK and RET fusions in Inner Mongolian patients. Additionally, we discovered eight novel fusion genes in three patients: SLC34A2-EPHB1, CCT6P3-GSTP1, BARHL2-APC, HRAS-MELK, FAM134B-ERBB2, ABCB1-GIPC1, GPR98-ALK, and FAM134B-SALL1. These previously unreported fusion genes suggest potential regional specificity. Furthermore, we characterized the fusion genes' structures based on breakpoints and described their impact on major functional gene domains. Importantly, the identified novel fusion genes exhibited significant clinical and pathological relevance. Notably, patients with SLC34A2-EPHB1, CCT6P3-GSTP1, and BARHL2-APC fusions showed sensitivity to the combination of chemotherapy and immunotherapy. Patients with HRAS-MELK, FAM134B-ERBB2, and ABCB1-GIPC1 fusions showed sensitivity to chemotherapy. In summary, our study provides novel insights into the frequency, distribution, and characteristics of specific fusion genes, offering valuable guidance for the development of effective clinical treatments, particularly in Inner Mongolia.
肺癌是全球癌症相关死亡的主要原因。基因融合是肿瘤发生的关键驱动因素，已经鉴定出许多用于肺癌诊断和治疗的驱动基因融合。然而，以前的研究主要集中在西方人群，由于内蒙古独特的遗传背景和饮食习惯，可能存在未被识别的与肺癌相关的特定基因融合。为了解决这个问题，我们对内蒙古 1200 名肺癌患者的肿瘤和相邻非肿瘤组织进行了 DNA 测序分析。我们的分析建立了内蒙古肺癌特有的全面融合基因景观，揭示了疾病潜在的区域特异性分子机制。与西方队列相比，我们观察到内蒙古患者中 ALK 和 RET 融合的发生率更高。此外，我们在三名患者中发现了八个新的融合基因：SLC34A2-EPHB1、CCT6P3-GSTP1、BARHL2-APC、HRAS-MELK、FAM134B-ERBB2、ABCB1-GIPC1、GPR98-ALK 和 FAM134B-SALL1。这些以前未报道的融合基因表明存在潜在的区域特异性。此外，我们基于断点对融合基因的结构进行了特征描述，并描述了它们对主要功能基因域的影响。重要的是，鉴定出的新融合基因具有显著的临床和病理相关性。值得注意的是，具有 SLC34A2-EPHB1、CCT6P3-GSTP1 和 BARHL2-APC 融合的患者对化疗和免疫治疗联合治疗敏感。具有 HRAS-MELK、FAM134B-ERBB2 和 ABCB1-GIPC1 融合的患者对化疗敏感。总之，我们的研究提供了关于特定融合基因的频率、分布和特征的新见解，为开发有效的临床治疗方法提供了有价值的指导，特别是在内蒙古。
