Latency and interval therapy affect the evolution in metastatic colorectal cancer

While comparison of primary tumor and metastases has highlighted genomic heterogeneity in colorectal cancer (CRC), previous studies have focused on a single metastatic site or limited genomic testing. Combining data from whole exome and ultra-deep targeted sequencing, we explored possible evolutiona...

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Bibliographic Details
Published in:Scientific reports Vol. 10; no. 1; p. 581
Main Authors: Nikbakht, Hamid, Jessa, Selin, Sukhai, Mahadeo A., Arseneault, Madeleine, Zhang, Tong, Letourneau, Louis, Thomas, Mariam, Bourgey, Mathieu, Roehrl, Michael H. A., Eveleigh, Robert, Chen, Eric X., Krzyzanowska, Monika, Moore, Malcolm J., Giesler, Amanda, Yu, Celeste, Bedard, Philippe L., Kamel-Reid, Suzanne, Majewski, Jacek, Siu, Lillian L., Riazalhosseini, Yasser, Graham, Donna M.
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 17.01.2020
Nature Publishing Group
Subjects:
45/22
45/23
631/67/69
692/4017
Colorectal cancer
Colorectal carcinoma
Colorectal Neoplasms - genetics
DNA Copy Number Variations
DNA Mutational Analysis
Evolution
Female
Gene Frequency
Gene Regulatory Networks
Genetic Heterogeneity
Heterogeneity
High-Throughput Nucleotide Sequencing
Humanities and Social Sciences
Humans
Latency
Lesions
Liver
Liver Neoplasms - genetics
Liver Neoplasms - secondary
Lung cancer
Lung Neoplasms - genetics
Lung Neoplasms - secondary
Male
Metastases
Metastasis
multidisciplinary
Mutation
Science
Science (multidisciplinary)
Time Factors
Tumors
Whole Exome Sequencing
ISSN:2045-2322, 2045-2322
Online Access:Get full text
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Summary:While comparison of primary tumor and metastases has highlighted genomic heterogeneity in colorectal cancer (CRC), previous studies have focused on a single metastatic site or limited genomic testing. Combining data from whole exome and ultra-deep targeted sequencing, we explored possible evolutionary trajectories beyond the status of these mutations, particularly among patient-matched metastatic tumors. Our findings confirm the persistence of known clinically-relevant mutations (e.g., those of RAS family of oncogenes) in CRC primary and metastases, yet reveal that latency and interval systemic therapy affect the course of evolutionary events within metastatic lesions. Specifically, our analysis of patient-matched primary and multiple metastatic lesions, developed over time, showed a similar genetic composition for liver metastatic tumors, which were 21-months apart. This genetic makeup was different from those identified in lung metastases developed before manifestation of the second liver metastasis. These results underscore the role of latency in the evolutionary path of metastatic CRC and may have implications for future treatment options.
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ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-020-57476-y