Department of Pathology, Faculty of Basic Medicine, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Institutes of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Bioinformatics, Burning Rock Biotech, Guangzhou, China.
Technol Cancer Res Treat. 2023 Jan-Dec;22:15330338231185285. doi: 10.1177/15330338231185285.
Primary tumor tissue is often analyzed to search for predictive biomarkers and DNA-guided personalized therapies, but there is an incomplete understanding of the discrepancies in the genomic profiles between primary tumors and metastases, such as liver and lung metastases.
We performed in-depth targeted next-generation sequencing of 520 key cancer-associated genes for 47 matched primary and metastatic tumor samples which were retrospectively collected.
A total of 699 mutations were detected in the 47 samples. The coincidence rate of primary tumors and metastases was 51.8% (n = 362), and compared to patients with liver metastases, patients with lung metastases had a significantly greater coincidence rate (.021). The number of specific mutations for the primary tumors and liver and lung metastases was 186 (26.6%), 122 (17.5%), and 29 (4.1%), respectively. Analysis of a patient with all three occurrences, including a primary tumor, liver metastasis, and lung metastasis, indicated a possible polyclonal seeding mechanism for liver metastases. Remarkably, multiple samples from patients with primary and metastatic tumors supported a mechanism of synchronous parallel dissemination from primary tumors to metastatic tumors that were not mediated through pre-metastatic tumors. We also found that the PI3K-Akt signaling pathway significantly altered lung metastases compared to matched primary tumors (.001). In addition, patients with mutations in or and or had larger primary tumor sizes and metastases, especially patients with both and mutations. Interestingly, CRC patients with -disruptive mutations were more likely to have liver metastases ( .016).
In this study, we demonstrate significant differences in the genomic landscapes of colorectal cancer patients based on the site of metastasis. Notably, we observe a larger genomic variation between primary tumors and liver metastasis compared to primary tumors and lung metastasis. These findings can be used for tailoring treatments based on the specific metastatic site.
通常分析原发肿瘤组织以寻找预测性生物标志物和基于 DNA 的个体化治疗，但对原发肿瘤和转移灶（如肝转移和肺转移）之间基因组谱的差异了解不完整。
我们对 47 对回顾性收集的匹配原发和转移肿瘤样本进行了 520 个关键癌症相关基因的深度靶向下一代测序。
在 47 个样本中总共检测到 699 个突变。原发肿瘤和转移灶的符合率为 51.8%（n=362），与肝转移患者相比，肺转移患者的符合率显著更高（0.021）。原发肿瘤和肝、肺转移灶的特定突变数分别为 186（26.6%）、122（17.5%）和 29（4.1%）。对一个同时存在原发肿瘤、肝转移和肺转移的患者进行分析，表明肝转移可能存在多克隆播种机制。值得注意的是，多个来自原发和转移肿瘤患者的样本支持原发肿瘤同步平行播散到转移灶的机制，而不是通过前转移灶介导的机制。我们还发现，PI3K-Akt 信号通路在肺转移灶与匹配的原发肿瘤相比显著改变（0.001）。此外，具有 或 或 或 突变的患者的原发肿瘤和转移灶更大，尤其是同时具有 和 突变的患者。有趣的是，CRC 患者具有 -破坏性突变更有可能发生肝转移（0.016）。
在这项研究中，我们根据转移部位证明了结直肠癌患者基因组景观存在显著差异。值得注意的是，我们观察到原发肿瘤和肝转移之间的基因组变异明显大于原发肿瘤和肺转移之间的变异。这些发现可用于根据特定的转移部位进行治疗。
