Whole genome sequencing of metastatic colorectal cancer reveals prior treatment effects and specific metastasis features.

Autor:	Mendelaar PAJ; Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands., Smid M; Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands., van Riet J; Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands.; Cancer Computational Biology Center, Erasmus MC Cancer Institute, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands.; Department of Urology, Erasmus MC Cancer Institute, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands., Angus L; Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands., Labots M; Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.; Center for Personalized Cancer Treatment, Rotterdam, The Netherlands., Steeghs N; Center for Personalized Cancer Treatment, Rotterdam, The Netherlands.; Department of Medical Oncology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek, Amsterdam, The Netherlands., Hendriks MP; Center for Personalized Cancer Treatment, Rotterdam, The Netherlands.; Department of Medical Oncology, Northwest Clinics, Alkmaar, The Netherlands., Cirkel GA; Center for Personalized Cancer Treatment, Rotterdam, The Netherlands.; Department of Medical Oncology, Meander Medical Center, Amersfoort, The Netherlands., van Rooijen JM; Center for Personalized Cancer Treatment, Rotterdam, The Netherlands.; Department of Medical Oncology, Martini Hospital, Groningen, The Netherlands., Ten Tije AJ; Center for Personalized Cancer Treatment, Rotterdam, The Netherlands.; Department of Medical Oncology, Amphia Hospital, Breda, The Netherlands., Lolkema MP; Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands.; Center for Personalized Cancer Treatment, Rotterdam, The Netherlands., Cuppen E; Center for Molecular Medicine and Oncode Institute, University Medical Center Utrecht, Utrecht, The Netherlands.; Hartwig Medical Foundation, Amsterdam, The Netherlands., Sleijfer S; Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands.; Center for Personalized Cancer Treatment, Rotterdam, The Netherlands., Martens JWM; Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands.; Center for Personalized Cancer Treatment, Rotterdam, The Netherlands., Wilting SM; Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands. s.wilting@erasmusmc.nl.
Jazyk:	angličtina
Zdroj:	Nature communications [Nat Commun] 2021 Jan 25; Vol. 12 (1), pp. 574. Date of Electronic Publication: 2021 Jan 25.
DOI:	10.1038/s41467-020-20887-6
Abstrakt:	In contrast to primary colorectal cancer (CRC) little is known about the genomic landscape of metastasized CRC. Here we present whole genome sequencing data of metastases of 429 CRC patients participating in the pan-cancer CPCT-02 study (NCT01855477). Unsupervised clustering using mutational signature patterns highlights three major patient groups characterized by signatures known from primary CRC, signatures associated with received prior treatments, and metastasis-specific signatures. Compared to primary CRC, we identify additional putative (non-coding) driver genes and increased frequencies in driver gene mutations. In addition, we identify specific genes preferentially affected by microsatellite instability. CRC-specific 1kb-10Mb deletions, enriched for common fragile sites, and LINC00672 mutations are associated with response to treatment in general, whereas FBXW7 mutations predict poor response specifically to EGFR-targeted treatment. In conclusion, the genomic landscape of mCRC shows defined changes compared to primary CRC, is affected by prior treatments and contains features with potential clinical relevance.
Databáze:	MEDLINE
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