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| Home > Publications database > Whole genome sequencing puts forward hypotheses on metastasis evolution and therapy in colorectal cancer. > print |
| 001 | 141414 | ||
| 005 | 20240229105126.0 | ||
| 024 | 7 | _ | |a 10.1038/s41467-018-07041-z |2 doi |
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| 037 | _ | _ | |a DKFZ-2018-01920 |
| 041 | _ | _ | |a eng |
| 082 | _ | _ | |a 500 |
| 100 | 1 | _ | |a Ishaque, Naveed |0 P:(DE-He78)4096eeffdfc73b75e8ba63dc621a017d |b 0 |e First author |u dkfz |
| 245 | _ | _ | |a Whole genome sequencing puts forward hypotheses on metastasis evolution and therapy in colorectal cancer. |
| 260 | _ | _ | |a [London] |c 2018 |b Nature Publishing Group UK |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1680780749_21951 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
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| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 520 | _ | _ | |a Incomplete understanding of the metastatic process hinders personalized therapy. Here we report the most comprehensive whole-genome study of colorectal metastases vs. matched primary tumors. 65% of somatic mutations originate from a common progenitor, with 15% being tumor- and 19% metastasis-specific, implicating a higher mutation rate in metastases. Tumor- and metastasis-specific mutations harbor elevated levels of BRCAness. We confirm multistage progression with new components ARHGEF7/ARHGEF33. Recurrently mutated non-coding elements include ncRNAs RP11-594N15.3, AC010091, SNHG14, 3 UTRs of FOXP2, DACH2, TRPM3, XKR4, ANO5, CBL, CBLB, the latter four potentially dual protagonists in metastasis and efferocytosis-/PD-L1 mediated immunosuppression. Actionable metastasis-specific lesions include FAT1, FGF1, BRCA2, KDR, and AKT2-, AKT3-, and PDGFRA-3 UTRs. Metastasis specific mutations are enriched in PI3K-Akt signaling, cell adhesion, ECM and hepatic stellate activation genes, suggesting genetic programs for site-specific colonization. Our results put forward hypotheses on tumor and metastasis evolution, and evidence for metastasis-specific events relevant for personalized therapy. |
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| 700 | 1 | _ | |a Abba, Mohammed L |b 1 |
| 700 | 1 | _ | |a Hauser, Christine |b 2 |
| 700 | 1 | _ | |a Patil, Nitin |b 3 |
| 700 | 1 | _ | |a Paramasivam, Nagarajan |0 P:(DE-He78)4a8b73f9f05542860120bb0e19527fd2 |b 4 |u dkfz |
| 700 | 1 | _ | |a Huebschmann, Daniel |0 P:(DE-He78)a5218e4871866cd5ab2312e594ca403d |b 5 |u dkfz |
| 700 | 1 | _ | |a Leupold, Jörg Hendrik |b 6 |
| 700 | 1 | _ | |a Balasubramanian, Gnana Prakash |0 P:(DE-HGF)0 |b 7 |
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| 700 | 1 | _ | |a Shavinskaya, Anna |b 12 |
| 700 | 1 | _ | |a Zhou, Chan |b 13 |
| 700 | 1 | _ | |a Gu, Zuguang |0 P:(DE-He78)73316f3cd41c27508dbb6f4c5e7e7a8a |b 14 |u dkfz |
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| 700 | 1 | _ | |a Marx, Alexander |b 16 |
| 700 | 1 | _ | |a Moniuszko, Marcin |b 17 |
| 700 | 1 | _ | |a Kozlowski, Miroslaw |b 18 |
| 700 | 1 | _ | |a Reszec, Joanna |b 19 |
| 700 | 1 | _ | |a Niklinski, Jacek |b 20 |
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| 700 | 1 | _ | |a Brors, Benedikt |0 P:(DE-He78)fc949170377b58098e46141d95c72661 |b 24 |u dkfz |
| 700 | 1 | _ | |a Allgayer, Heike |b 25 |
| 773 | _ | _ | |a 10.1038/s41467-018-07041-z |g Vol. 9, no. 1, p. 4782 |0 PERI:(DE-600)2553671-0 |n 1 |p 4782 |t Nature Communications |v 9 |y 2018 |x 2041-1723 |
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