دورية أكاديمية
Whole-genome characterization of lung adenocarcinomas lacking the RTK/RAS/RAF pathway
| العنوان: | Whole-genome characterization of lung adenocarcinomas lacking the RTK/RAS/RAF pathway |
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| المؤلفون: | Carrot-Zhang, J., Yao, X., Devarakonda, S., Deshpande, A., Damrauer, J.S., Silva, T.C., Wong, C.K., Choi, H.Y., Felau, I., Robertson, A.G., Castro, M.A.A., Bao, L., Rheinbay, E., Liu, E.M., Trieu, T., Haan, D., Yau, C., Hinoue, T., Liu, Y., Shapira, O., Kumar, K., Mungall, K.L., Zhang, H., Lee, J.J.-K., Berger, A., Gao, G.F., Zhitomirsky, B., Liang, W.-W., Zhou, M., Moorthi, S., Berger, A.H., Collisson, E.A., Zody, M.C., Ding, L., Cherniack, A.D., Getz, G., Elemento, O., Benz, C.C., Stuart, J., Zenklusen, J.C., Beroukhim, R., Chang, J.C., Campbell, J.D., Hayes, D.N., Yang, L., Laird, P.W., Weinstein, J.N., Kwiatkowski, D.J., Tsao, M.S., Travis, W.D., Khurana, E., Berman, B.P., Hoadley, K.A., Robine, N., TCGA Research Network, Meyerson, M., Govindan, R., Imielinski, M. |
| المصدر: | Cell Reports, 34(5) |
| بيانات النشر: | Elsevier B.V. |
| سنة النشر: | 2021 |
| المجموعة: | Carolina Digital Repository (UNC - University of North Carolina) |
| مصطلحات موضوعية: | lung adenocarcinoma, tumor suppressor, TCGA, driver, genome analysis, noncoding, precision oncology, whole genome sequencing, structural variation, oncogene |
| الوصف: | RTK/RAS/RAF pathway alterations (RPAs) are a hallmark of lung adenocarcinoma (LUAD). In this study, we use whole-genome sequencing (WGS) of 85 cases found to be RPA(−) by previous studies from The Cancer Genome Atlas (TCGA) to characterize the minority of LUADs lacking apparent alterations in this pathway. We show that WGS analysis uncovers RPA(+) in 28 (33%) of the 85 samples. Among the remaining 57 cases, we observe focal deletions targeting the promoter or transcription start site of STK11 (n = 7) or KEAP1 (n = 3), and promoter mutations associated with the increased expression of ILF2 (n = 6). We also identify complex structural variations associated with high-level copy number amplifications. Moreover, an enrichment of focal deletions is found in TP53 mutant cases. Our results indicate that RPA(−) cases demonstrate tumor suppressor deletions and genome instability, but lack unique or recurrent genetic lesions compensating for the lack of RPAs. Larger WGS studies of RPA(−) cases are required to understand this important LUAD subset. © 2021 The AuthorsCarrot-Zhang et al. perform whole-genome characterization of lung adenocarcinomas (LUADs) lacking RTK/RAS/RAF pathway alterations (RPAs) and identify mutations or structural variants in both coding and non-coding spaces that define a unique entity of RPA(−) LUADs and potentially explain the underlying biology of this disease. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | https://doi.org/10.17615/r3x4-ht75Test; https://cdr.lib.unc.edu/downloads/9z903808j?file=thumbnailTest; https://cdr.lib.unc.edu/downloads/9z903808jTest |
| DOI: | 10.17615/r3x4-ht75 |
| الإتاحة: | https://doi.org/10.17615/r3x4-ht75Test https://cdr.lib.unc.edu/downloads/9z903808j?file=thumbnailTest https://cdr.lib.unc.edu/downloads/9z903808jTest |
| رقم الانضمام: | edsbas.8B67084C |
| قاعدة البيانات: | BASE |
| DOI: | 10.17615/r3x4-ht75 |
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