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学術論文

Integrative genomic analyses reveal an androgen-driven somatic alteration landscape in early-onset prostate cancer

MPS-Authors

Schlangen,  K.
Department of Biomedical Optics, Max Planck Institute for Medical Research, Max Planck Society;

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Warnatz,  H. J.
Department of Biomedical Optics, Max Planck Institute for Medical Research, Max Planck Society;

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Stehr,  H.
Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Amstislavskiy,  V.
Human Chromosome 21 (Marie-Laure Yaspo), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Lehrach,  H.
Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Parkhomchuk,  D.
Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Sultan,  M.
Human Chromosome 21 (Marie-Laure Yaspo), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Yaspo Lehrach,  Marie L.
Human Chromosome 21 (Marie-Laure Yaspo), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Weischenfeldt.pdf
(出版社版), 2MB

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引用

Weischenfeldt, J., Simon, R., Feuerbach, L., Schlangen, K., Weichenhan, D., Minner, S., Wuttig, D., Warnatz, H. J., Stehr, H., Rausch, T., Jager, N., Gu, L., Bogatyrova, O., Stutz, A. M., Claus, R., Eils, J., Eils, R., Gerhauser, C., Huang, P. H., Hutter, B., Kabbe, R., Lawerenz, C., Radomski, S., Bartholomae, C. C., Falth, M., Gade, S., Schmidt, M., Amschler, N., Hass, T., Galal, R., Gjoni, J., Kuner, R., Baer, C., Masser, S., von Kalle, C., Zichner, T., Benes, V., Raeder, B., Mader, M., Amstislavskiy, V., Avci, M., Lehrach, H., Parkhomchuk, D., Sultan, M., Burkhardt, L., Graefen, M., Huland, H., Kluth, M., Krohn, A., Sirma, H., Stumm, L., Steurer, S., Grupp, K., Sultmann, H., Sauter, G., Plass, C., Brors, B., Yaspo Lehrach, M. L., Korbel, J. O., & Schlomm, T. (2013). Integrative genomic analyses reveal an androgen-driven somatic alteration landscape in early-onset prostate cancer. Cancer Cell, 23(2), 159-70. doi:S1535-6108(13)00004-4 [pii]10.1016/j.ccr.2013.01.002.


引用: https://hdl.handle.net/11858/00-001M-0000-0018-F403-0
要旨
Early-onset prostate cancer (EO-PCA) represents the earliest clinical manifestation of prostate cancer. To compare the genomic alteration landscapes of EO-PCA with "classical" (elderly-onset) PCA, we performed deep sequencing-based genomics analyses in 11 tumors diagnosed at young age, and pursued comparative assessments with seven elderly-onset PCA genomes. Remarkable age-related differences in structural rearrangement (SR) formation became evident, suggesting distinct disease pathomechanisms. Whereas EO-PCAs harbored a prevalence of balanced SRs, with a specific abundance of androgen-regulated ETS gene fusions including TMPRSS2:ERG, elderly-onset PCAs displayed primarily non-androgen-associated SRs. Data from a validation cohort of > 10,000 patients showed age-dependent androgen receptor levels and a prevalence of SRs affecting androgen-regulated genes, further substantiating the activity of a characteristic "androgen-type" pathomechanism in EO-PCA.