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Genetic and microenvironmental intra-tumor heterogeneity impacts colorectal cancer evolution and metastatic development. | LitMetric

AI Article Synopsis

  • - Colorectal cancer (CRC) exhibits significant genetic diversity influenced by various genomic instability pathways, resulting in differences within tumors and their surrounding environments.
  • - A study of 136 CRC samples revealed that this diversity arises from molecular alterations that occur at different rates, with certain genomic features being better predictors of heterogeneity in tumor subtypes and locations.
  • - The research indicates that higher levels of genetic and microenvironment diversity are linked to a reduced likelihood of metastasis, while certain genetic changes that appear later may promote the spread of cancer cells.

Article Abstract

Colorectal cancer (CRC) is a highly diverse disease, where different genomic instability pathways shape genetic clonal diversity and tumor microenvironment. Although intra-tumor heterogeneity has been characterized in primary tumors, its origin and consequences in CRC outcome is not fully understood. Therefore, we assessed intra- and inter-tumor heterogeneity of a prospective cohort of 136 CRC samples. We demonstrate that CRC diversity is forged by asynchronous forms of molecular alterations, where mutational and chromosomal instability collectively boost CRC genetic and microenvironment intra-tumor heterogeneity. We were able to depict predictor signatures of cancer-related genes that can foresee heterogeneity levels across the different tumor consensus molecular subtypes (CMS) and primary tumor location. Finally, we show that high genetic and microenvironment heterogeneity are associated with lower metastatic potential, whereas late-emerging copy number variations favor metastasis development and polyclonal seeding. This study provides an exhaustive portrait of the interplay between genetic and microenvironment intra-tumor heterogeneity across CMS subtypes, depicting molecular events with predictive value of CRC progression and metastasis development.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9463147PMC
http://dx.doi.org/10.1038/s42003-022-03884-xDOI Listing

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