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  Hypermutation of the inactive X chromosome is a frequent event in cancer

Jager, N., Schlesner, M., Jones, D. T., Raffel, S., Mallm, J. P., Junge, K. M., et al. (2013). Hypermutation of the inactive X chromosome is a frequent event in cancer. Cell, 155(3), 567-81. doi:S0092-8674(13)01216-6 [pii]10.1016/j.cell.2013.09.042.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0019-0861-A Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0019-0867-D
Genre: Journal Article

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Jäger.pdf (Publisher version), 2MB
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Copyright Date:
2013
Copyright Info:
2013 Elsevier Inc.

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 Creators:
Jager, N., Author
Schlesner, M., Author
Jones, D. T., Author
Raffel, S., Author
Mallm, J. P., Author
Junge, K. M., Author
Weichenhan, D., Author
Bauer, T., Author
Ishaque, N., Author
Kool, M., Author
Northcott, P. A., Author
Korshunov, A., Author
Drews, R. M., Author
Koster, J., Author
Versteeg, R., Author
Richter, J., Author
Hummel, M., Author
Mack, S. C., Author
Taylor, M. D., Author
Witt, H., Author
Swartman, B., AuthorSchulte-Bockholt, D., AuthorSultan, M.1, Author              Yaspo, M. L.1, Author              Lehrach, H.2, Author              Hutter, B., AuthorBrors, B., AuthorWolf, S., AuthorPlass, C., AuthorSiebert, R., AuthorTrumpp, A., AuthorRippe, K., AuthorLehmann, I., AuthorLichter, P., AuthorPfister, S. M., AuthorEils, R., Author more..
Affiliations:
1Human Chromosome 21 (Marie-Laure Yaspo), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479652              
2Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433550              

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Free keywords: Adult Aged *Chromosomes, Human, X DNA Replication Female Humans Male Medulloblastoma/genetics/pathology *Mutation Myelodysplastic Syndromes/genetics/pathology Neoplasms/*genetics Polymorphism, Single Nucleotide S Phase *X Chromosome Inactivation
 Abstract: Mutation is a fundamental process in tumorigenesis. However, the degree to which the rate of somatic mutation varies across the human genome and the mechanistic basis underlying this variation remain to be fully elucidated. Here, we performed a cross-cancer comparison of 402 whole genomes comprising a diverse set of childhood and adult tumors, including both solid and hematopoietic malignancies. Surprisingly, we found that the inactive X chromosome of many female cancer genomes accumulates on average twice and up to four times as many somatic mutations per megabase, as compared to the individual autosomes. Whole-genome sequencing of clonally expanded hematopoietic stem/progenitor cells (HSPCs) from healthy individuals and a premalignant myelodysplastic syndrome (MDS) sample revealed no X chromosome hypermutation. Our data suggest that hypermutation of the inactive X chromosome is an early and frequent feature of tumorigenesis resulting from DNA replication stress in aberrantly proliferating cells.

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Language(s): eng - English
 Dates: 2013-08-022013-04-272013-09-202013-10-172013
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: -
 Degree: -

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Title: Cell
Source Genre: Journal
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Publ. Info: Cambridge, Mass. : Cell Press
Pages: 15 Volume / Issue: 155 (3) Sequence Number: - Start / End Page: 567 - 81 Identifier: ISSN: 0092-8674
CoNE: https://pure.mpg.de/cone/journals/resource/954925463183