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000141414 1001_ $$0P:(DE-He78)4096eeffdfc73b75e8ba63dc621a017d$$aIshaque, Naveed$$b0$$eFirst author$$udkfz
000141414 245__ $$aWhole genome sequencing puts forward hypotheses on metastasis evolution and therapy in colorectal cancer.
000141414 260__ $$a[London]$$bNature Publishing Group UK$$c2018
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000141414 520__ $$aIncomplete 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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000141414 7001_ $$aAbba, Mohammed L$$b1
000141414 7001_ $$aHauser, Christine$$b2
000141414 7001_ $$aPatil, Nitin$$b3
000141414 7001_ $$0P:(DE-He78)4a8b73f9f05542860120bb0e19527fd2$$aParamasivam, Nagarajan$$b4$$udkfz
000141414 7001_ $$0P:(DE-He78)a5218e4871866cd5ab2312e594ca403d$$aHuebschmann, Daniel$$b5$$udkfz
000141414 7001_ $$aLeupold, Jörg Hendrik$$b6
000141414 7001_ $$0P:(DE-HGF)0$$aBalasubramanian, Gnana Prakash$$b7
000141414 7001_ $$0P:(DE-He78)e053817bc90becc8a8dd8250e677e773$$aKleinheinz, Kortine$$b8$$udkfz
000141414 7001_ $$0P:(DE-He78)cd8295952c28dc5b483b5ba9386a5669$$aToprak, Umut$$b9$$udkfz
000141414 7001_ $$0P:(DE-He78)135e8c8d1dd1b66b8127c3d1e3a9b6a0$$aHutter, Barbara$$b10$$udkfz
000141414 7001_ $$0P:(DE-He78)e15dfa1260625c69d6690a197392a994$$aBenner, Axel$$b11$$udkfz
000141414 7001_ $$aShavinskaya, Anna$$b12
000141414 7001_ $$aZhou, Chan$$b13
000141414 7001_ $$0P:(DE-He78)73316f3cd41c27508dbb6f4c5e7e7a8a$$aGu, Zuguang$$b14$$udkfz
000141414 7001_ $$0P:(DE-He78)ceb63355dafa7f7576123ee3828b8820$$aKerssemakers, Jules$$b15$$udkfz
000141414 7001_ $$aMarx, Alexander$$b16
000141414 7001_ $$aMoniuszko, Marcin$$b17
000141414 7001_ $$aKozlowski, Miroslaw$$b18
000141414 7001_ $$aReszec, Joanna$$b19
000141414 7001_ $$aNiklinski, Jacek$$b20
000141414 7001_ $$0P:(DE-He78)442f4a5d2d41f01896229fac4d339d45$$aEils, Jürgen$$b21$$udkfz
000141414 7001_ $$0P:(DE-He78)f2a782242acf94a3114d75c45dc75b37$$aSchlesner, Matthias$$b22$$udkfz
000141414 7001_ $$0P:(DE-He78)78b6aa82148e60b4d91e3a37a6d3d9a0$$aEils, Roland$$b23$$udkfz
000141414 7001_ $$0P:(DE-He78)fc949170377b58098e46141d95c72661$$aBrors, Benedikt$$b24$$udkfz
000141414 7001_ $$aAllgayer, Heike$$b25
000141414 773__ $$0PERI:(DE-600)2553671-0$$a10.1038/s41467-018-07041-z$$gVol. 9, no. 1, p. 4782$$n1$$p4782$$tNature Communications$$v9$$x2041-1723$$y2018
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