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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Vydané v:	Scientific reports Ročník 10; číslo 1; s. 581
Hlavní autori:	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.
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	London Nature Publishing Group UK 17.01.2020 Nature Publishing Group
Predmet:	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
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Abstract	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.
AbstractList	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. 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.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.
ArticleNumber	581
Author	Giesler, Amanda Yu, Celeste Graham, Donna M. Thomas, Mariam Nikbakht, Hamid Bourgey, Mathieu Siu, Lillian L. Kamel-Reid, Suzanne Bedard, Philippe L. Jessa, Selin Sukhai, Mahadeo A. Arseneault, Madeleine Eveleigh, Robert Letourneau, Louis Zhang, Tong Krzyzanowska, Monika Majewski, Jacek Moore, Malcolm J. Roehrl, Michael H. A. Chen, Eric X. Riazalhosseini, Yasser
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CitedBy_id	crossref_primary_10_1186_s12967_021_03062_3 crossref_primary_10_3390_cancers12102808 crossref_primary_10_1016_j_semcancer_2021_05_007 crossref_primary_10_3390_cancers14133078
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Snippet	While comparison of primary tumor and metastases has highlighted genomic heterogeneity in colorectal cancer (CRC), previous studies have focused on a single...
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SubjectTerms	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
Title	Latency and interval therapy affect the evolution in metastatic colorectal cancer
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