AU  - Mendelaar, Pauline A. J.
AU  - Smid, Marcel
AU  - van Riet, Job
AU  - Angus, Lindsay
AU  - Labots, Mariette
AU  - Steeghs, Neeltje
AU  - Hendriks, Mathijs P.
AU  - Cirkel, Geert A.
AU  - van Rooijen, Johan M.
AU  - Ten Tije, Albert J.
AU  - Lolkema, Martijn P.
AU  - Cuppen, Edwin
AU  - Sleijfer, Stefan
AU  - Martens, John W. M.
AU  - Wilting, Saskia M.
TI  - Whole genome sequencing of metastatic colorectal cancer reveals prior treatment effects and specific metastasis features
JO  - Nature Communications
VL  - 12
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Nature Publishing Group UK
M1  - DKFZ-2022-01691
SP  - 574
PY  - 2021
AB  - In contrast to primary colorectal cancer (CRC) little is known about the genomic landscape ofmetastasized CRC. Here we present whole genome sequencing data of metastases of 429CRC patients participating in the pan-cancer CPCT-02 study (NCT01855477). Unsupervisedclustering using mutational signature patterns highlights three major patient groups characterized by signatures known from primary CRC, signatures associated with received priortreatments, and metastasis-specific signatures. Compared to primary CRC, we identifyadditional putative (non-coding) driver genes and increased frequencies in driver genemutations. In addition, we identify specific genes preferentially affected by microsatelliteinstability. CRC-specific 1kb-10Mb deletions, enriched for common fragile sites, andLINC00672 mutations are associated with response to treatment in general, whereas FBXW7mutations predict poor response specifically to EGFR-targeted treatment. In conclusion, thegenomic landscape of mCRC shows defined changes compared to primary CRC, is affectedby prior treatments and contains features with potential clinical relevance.
LB  - PUB:(DE-HGF)16
DO  - DOI:10.1038/s41467-020-20887-6
UR  - https://inrepo02.dkfz.de/record/180966
ER  -