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000304848 1001_ $$0P:(DE-He78)6e4c1c3a625649efed69595001ff1e5e$$aDiaz Jimenez, Alberto$$b0$$eFirst author
000304848 245__ $$aEML4-ALK variant-specific genetic interactions shape lung tumorigenesis.
000304848 260__ $$aPhiladelphia, Pa.$$b[Verlag nicht ermittelbar]$$c2026
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000304848 520__ $$aDiverse fusions of EML4 and ALK are oncogenic drivers in lung adenocarcinomas. EML4-ALK variants have distinct breakpoints within EML4, but their functional differences remain poorly understood. Here, we use somatic genome editing to generate autochthonous mouse models of EML4-ALK-driven lung tumors and show that V3 is more oncogenic than V1. By employing multiplexed genome editing and quantifying the effects of 29 putative tumor suppressor genes on V1- and V3-driven lung cancer growth, we show that many tumor suppressor genes have variant-specific effects on tumorigenesis. Pharmacogenomic analyses further suggest that tumor genotype can influence therapeutic responses. Analysis of human EML4-ALK-positive lung cancers also identified variant-specific differences in their genomic landscapes. These findings suggest that EML4-ALK variants behave more like distinct oncogenes rather than a uniform entity and highlight the dramatic impact of oncogenic fusion partner proteins and coincident tumor suppressor gene alterations on the biology of oncogenic fusion-driven cancers.
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000304848 7001_ $$00000-0002-5018-0500$$aShuldiner, Emily G$$b1
000304848 7001_ $$0P:(DE-He78)1a99792a8cdba2d016336662bb5c1099$$aSomogyi, Kalman$$b2$$udkfz
000304848 7001_ $$00000-0001-7669-1643$$aShih, Karen$$b3
000304848 7001_ $$0P:(DE-He78)32e902dfbb03aa0614f4864d149b1266$$aGonzalez Velasco, Oscar$$b4$$udkfz
000304848 7001_ $$0P:(DE-He78)e8ba111d3edfcdc89a3c0eea339aa270$$aNajajreh, Mulham$$b5$$udkfz
000304848 7001_ $$00000-0001-7196-0541$$aKim, Stewart$$b6
000304848 7001_ $$0P:(DE-He78)c433c3d2a50f03793807ffc4d8516237$$aAkkas, Filiz$$b7$$udkfz
000304848 7001_ $$00000-0001-7027-892X$$aMurray, Christopher W$$b8
000304848 7001_ $$00000-0002-2202-5626$$aAndrejka, Laura$$b9
000304848 7001_ $$aTsai, Min K$$b10
000304848 7001_ $$0P:(DE-He78)fc949170377b58098e46141d95c72661$$aBrors, Benedikt$$b11$$udkfz
000304848 7001_ $$0P:(DE-He78)0c4543046185361a644540fee0dad8b1$$aHofmann, Ilse$$b12$$udkfz
000304848 7001_ $$00000-0001-7790-5615$$aSivakumar, Smruthy$$b13
000304848 7001_ $$00000-0001-7276-8084$$aSisoudiya, Saumya D$$b14
000304848 7001_ $$00000-0002-5480-8473$$aSokol, Ethan S$$b15
000304848 7001_ $$00000-0002-5921-5773$$aCai, Hongchen$$b16
000304848 7001_ $$00000-0002-3664-9130$$aPetrov, Dmitri A$$b17
000304848 7001_ $$00000-0002-5730-9573$$aWinslow, Monte M$$b18
000304848 7001_ $$00000-0002-0855-7917$$aSotillo, Rocio$$b19$$eLast author
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