Endocrine and Sarcoma Surgery, Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Department of Endocrine and Sarcoma Surgery, Surgical Clinic SU/S, Sahlgrenska University Hospital, Gothenburg, Sweden.
Nat Commun. 2021 Nov 4;12(1):6367. doi: 10.1038/s41467-021-26581-5.
Small intestine neuroendocrine tumor (SI-NET), the most common cancer of the small bowel, often displays a curious multifocal phenotype with several tumors clustered together in a limited intestinal segment. SI-NET also shows an unusual absence of driver mutations explaining tumor initiation and metastatic spread. The evolutionary trajectories that underlie multifocal SI-NET lesions could provide insight into the underlying tumor biology, but this question remains unresolved. Here, we determine the complete genome sequences of 61 tumors and metastases from 11 patients with multifocal SI-NET, allowing for elucidation of phylogenetic relationships between tumors within single patients. Intra-individual comparisons revealed a lack of shared somatic single-nucleotide variants among the sampled intestinal lesions, supporting an independent clonal origin. Furthermore, in three of the patients, two independent tumors had metastasized. We conclude that primary multifocal SI-NETs generally arise from clonally independent cells, suggesting a contribution from a cancer-priming local factor.
小肠类癌肿瘤（SI-NET）是小肠最常见的癌症，通常表现出一种奇特的多灶性表型，即在有限的肠段内聚集在一起的多个肿瘤。SI-NET 还表现出一种异常的缺乏驱动突变的情况，这些突变解释了肿瘤的起始和转移扩散。支持多灶性 SI-NET 病变的进化轨迹可以深入了解肿瘤的生物学基础，但这个问题仍未得到解决。在这里，我们确定了 11 名多灶性 SI-NET 患者的 61 个肿瘤和转移瘤的全基因组序列，从而能够阐明单个患者内肿瘤之间的系统发育关系。个体内比较显示，所采样的肠道病变之间缺乏共享的体细胞单核苷酸变异，支持独立的克隆起源。此外，在其中 3 名患者中，两个独立的肿瘤发生了转移。我们得出结论，原发性多灶性 SI-NET 通常来自于克隆独立的细胞，这表明局部致癌因素的贡献。
