Latency and interval therapy affect the evolution in metastatic colorectal cancer.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
17 01 2020
17 01 2020
Historique:
received:
19
10
2017
accepted:
27
12
2019
entrez:
19
1
2020
pubmed:
19
1
2020
medline:
20
11
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 31953485
doi: 10.1038/s41598-020-57476-y
pii: 10.1038/s41598-020-57476-y
pmc: PMC6969060
doi:
Types de publication
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
581Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
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