A unique interplay of access and selection shapes peritoneal metastasis evolution in colorectal cancer.

Autor:	Wassenaar EC; Department of Surgery, St. Antonius Hospital, Nieuwegein, the Netherlands.; Department of Surgical Oncology, Laboratory Translational Oncology, University Medical Center Utrecht, Utrecht, the Netherlands., Gorelick AN; Department of Genetics, Harvard Medical School, Boston, MA, USA.; Center for Systems Biology, Massachusetts General Hospital Research Institute and Harvard Medical School, Boston, MA, USA., Hung WT; Center for Systems Biology, Massachusetts General Hospital Research Institute and Harvard Medical School, Boston, MA, USA.; Present address: Graduate Institute of Medical Genomics and Proteomics, National Taiwan University, Taipei, Taiwan., Cheek DM; Department of Genetics, Harvard Medical School, Boston, MA, USA.; Center for Systems Biology, Massachusetts General Hospital Research Institute and Harvard Medical School, Boston, MA, USA., Kucukkose E; Department of Surgical Oncology, Laboratory Translational Oncology, University Medical Center Utrecht, Utrecht, the Netherlands., Lee IH; Department of Genetics, Harvard Medical School, Boston, MA, USA.; Center for Systems Biology, Massachusetts General Hospital Research Institute and Harvard Medical School, Boston, MA, USA., Blohmer M; Department of Genetics, Harvard Medical School, Boston, MA, USA.; Center for Systems Biology, Massachusetts General Hospital Research Institute and Harvard Medical School, Boston, MA, USA.; Charité - Universitätsmedizin Berlin, Berlin, Germany., Degner S; Department of Genetics, Harvard Medical School, Boston, MA, USA.; Center for Systems Biology, Massachusetts General Hospital Research Institute and Harvard Medical School, Boston, MA, USA., Giunta P; Department of Genetics, Harvard Medical School, Boston, MA, USA.; Center for Systems Biology, Massachusetts General Hospital Research Institute and Harvard Medical School, Boston, MA, USA., Wiezer RM; Department of Surgery, St. Antonius Hospital, Nieuwegein, the Netherlands., Raicu MG; Department of Pathology, St. Antonius Hospital, Nieuwegein, the Netherlands.; Oncode Institute, Hubrecht Institute-KNAW (Royal Academy of Arts and Sciences) and University Medical Centre Utrecht, Utrecht, the Netherlands., Ubink I; Department of Surgical Oncology, Laboratory Translational Oncology, University Medical Center Utrecht, Utrecht, the Netherlands., Klaasen SJ; Oncode Institute, Hubrecht Institute-KNAW (Royal Academy of Arts and Sciences) and University Medical Centre Utrecht, Utrecht, the Netherlands., Lansu N; Oncode Institute, Hubrecht Institute-KNAW (Royal Academy of Arts and Sciences) and University Medical Centre Utrecht, Utrecht, the Netherlands., Watson EV; University of Massachusetts Medical School, Worcester, MA, USA., Corcoran RB; Division of Hematology and Oncology, Department of Medicine, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA., Boland G; Division of Surgical Oncology, Department of Surgery, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.; Krantz Family Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA., Getz G; Krantz Family Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA.; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Department of Pathology, Massachusetts General Hospital, Boston, MA, USA., Kops GJ; Oncode Institute, Hubrecht Institute-KNAW (Royal Academy of Arts and Sciences) and University Medical Centre Utrecht, Utrecht, the Netherlands., Juric D; Krantz Family Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA.; Termeer Center for Targeted Therapies, Massachusetts General Hospital, Boston, MA, USA., Lennerz JK; Department of Pathology, Massachusetts General Hospital, Boston, MA, USA., Boerma D; Department of Surgery, St. Antonius Hospital, Nieuwegein, the Netherlands., Kranenburg O; Department of Surgical Oncology, Laboratory Translational Oncology, University Medical Center Utrecht, Utrecht, the Netherlands., Naxerova K; Department of Genetics, Harvard Medical School, Boston, MA, USA.; Center for Systems Biology, Massachusetts General Hospital Research Institute and Harvard Medical School, Boston, MA, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Sep 27. Date of Electronic Publication: 2024 Sep 27.
DOI:	10.1101/2024.09.25.614736
Abstrakt:	Whether metastasis in humans can be accomplished by most primary tumor cells or requires the evolution of a specialized trait remains an open question. To evaluate whether metastases are founded by non-random subsets of primary tumor lineages requires extensive, difficult-to-implement sampling. We have realized an unusually dense multi-region sampling scheme in a cohort of 26 colorectal cancer patients with peritoneal metastases, reconstructing the evolutionary history of on average 28.8 tissue samples per patient with a microsatellite-based fingerprinting assay. To assess metastatic randomness, we evaluate inter- and intra-metastatic heterogeneity relative to the primary tumor and find that peritoneal metastases are more heterogeneous than liver metastases but less diverse than locoregional metastases. Metachronous peritoneal metastases exposed to systemic chemotherapy show significantly higher inter-lesion diversity than synchronous, untreated metastases. Projection of peritoneal metastasis origins onto a spatial map of the primary tumor reveals that they often originate at the deep-invading edge, in contrast to liver and lymph node metastases which exhibit no such preference. Furthermore, peritoneal metastases typically do not share a common subclonal origin with distant metastases in more remote organs. Synthesizing these insights into an evolutionary portrait of peritoneal metastases, we conclude that the peritoneal-metastatic process imposes milder selective pressures onto disseminating cancer cells than the liver-metastatic process. Peritoneal metastases' unique evolutionary features have potential implications for staging and treatment. Competing Interests: Competing financial interests The authors declare no competing financial interests.
Databáze:	MEDLINE
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