Independent somatic evolution underlies clustered neuroendocrine tumors in the human small intestine

Erik Elias, Arman Ardalan, Markus Lindberg, Susanne E. Reinsbach, Andreas Muth, Ola Nilsson, Yvonne Arvidsson and Erik Larsson ()
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Erik Elias: Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg
Arman Ardalan: Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg
Markus Lindberg: Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg
Susanne E. Reinsbach: Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg
Andreas Muth: Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg
Ola Nilsson: Institute of Biomedicine, Sahlgrenska Cancer Center, Sahlgrenska Academy at University of Gothenburg
Yvonne Arvidsson: Sahlgrenska University Hospital
Erik Larsson: Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg

Nature Communications, 2021, vol. 12, issue 1, 1-8

Abstract: Abstract 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.

Date: 2021
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DOI: 10.1038/s41467-021-26581-5

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