Department of Abdominal Oncology, SSD-Innovative Therapies for Abdominal Cancers, Istituto Nazionale Tumori di Napoli, IRCCS "G. Pascale", , Via M. Semmola, 80131, Naples, Italy.
AMES-Centro Polidiagnostico Strumentale, Srl, Naples, Italy.
Cell Death Dis. 2020 Apr 24;11(4):275. doi: 10.1038/s41419-020-2480-6.
Genetics and immunologic dynamics pushing the evolution of colorectal cancer (CRC) from the primary tumor to the metastases are largely unknown; cancer heterogeneity makes challenging both therapy and mechanistic studies. We selected patients developing CRC with lung-limited metastatic disease as only illness during their life in order to find any relevant genotype-phenotype relationship. Analysis of 523 cancer-relevant genes and of immune cells infiltration in primary and metastatic tissues revealed atypical genomic trajectories (TMB decrease, KRAS and SMAD4 regressive mutations), specific genetic events (ERBB2 point mutations) and scarce T-cell infiltration. These insights provide novel information in oligometastatic CRC biology and new perspectives for cancer monitoring and anti-cancer therapeutic strategies.
推动结直肠癌（CRC）从原发性肿瘤到转移瘤的遗传和免疫动力学在很大程度上是未知的；癌症异质性使得治疗和机制研究都具有挑战性。我们选择了在其一生中仅患有肺部局限性转移疾病的 CRC 患者，以便找到任何相关的基因型-表型关系。对 523 个与癌症相关的基因和原发性和转移性组织中免疫细胞浸润的分析揭示了非典型的基因组轨迹（TMB 降低、KRAS 和 SMAD4 退行性突变）、特定的遗传事件（ERBB2 点突变）和稀少的 T 细胞浸润。这些见解为寡转移性 CRC 生物学提供了新的信息，并为癌症监测和抗癌治疗策略提供了新的视角。
