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| 001 | 304848 | ||
| 005 | 20260112160902.0 | ||
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| 100 | 1 | _ | |a Diaz Jimenez, Alberto |0 P:(DE-He78)6e4c1c3a625649efed69595001ff1e5e |b 0 |e First author |
| 245 | _ | _ | |a EML4-ALK variant-specific genetic interactions shape lung tumorigenesis. |
| 260 | _ | _ | |a Philadelphia, Pa. |c 2026 |b [Verlag nicht ermittelbar] |
| 336 | 7 | _ | |a article |2 DRIVER |
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| 500 | _ | _ | |a #EA:B220#LA:B220# / 2026 Jan 12;16(1):46-65 |
| 520 | _ | _ | |a Diverse 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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| 700 | 1 | _ | |a Shuldiner, Emily G |0 0000-0002-5018-0500 |b 1 |
| 700 | 1 | _ | |a Somogyi, Kalman |0 P:(DE-He78)1a99792a8cdba2d016336662bb5c1099 |b 2 |u dkfz |
| 700 | 1 | _ | |a Shih, Karen |0 0000-0001-7669-1643 |b 3 |
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| 700 | 1 | _ | |a Kim, Stewart |0 0000-0001-7196-0541 |b 6 |
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| 700 | 1 | _ | |a Murray, Christopher W |0 0000-0001-7027-892X |b 8 |
| 700 | 1 | _ | |a Andrejka, Laura |0 0000-0002-2202-5626 |b 9 |
| 700 | 1 | _ | |a Tsai, Min K |b 10 |
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| 700 | 1 | _ | |a Sivakumar, Smruthy |0 0000-0001-7790-5615 |b 13 |
| 700 | 1 | _ | |a Sisoudiya, Saumya D |0 0000-0001-7276-8084 |b 14 |
| 700 | 1 | _ | |a Sokol, Ethan S |0 0000-0002-5480-8473 |b 15 |
| 700 | 1 | _ | |a Cai, Hongchen |0 0000-0002-5921-5773 |b 16 |
| 700 | 1 | _ | |a Petrov, Dmitri A |0 0000-0002-3664-9130 |b 17 |
| 700 | 1 | _ | |a Winslow, Monte M |0 0000-0002-5730-9573 |b 18 |
| 700 | 1 | _ | |a Sotillo, Rocio |0 0000-0002-0855-7917 |b 19 |e Last author |
| 773 | _ | _ | |a 10.1158/2159-8290.CD-24-1417 |0 PERI:(DE-600)2607892-2 |n 1 |p 46-65 |t Cancer discovery |v 16 |y 2026 |x 2159-8274 |
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