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Genomic and functional overlap between somatic and germline chromosomal rearrangements

(2014) CELL REPORTS. 9(6). p.2001-2010
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Abstract
Genomic rearrangements are a common cause of human congenital abnormalities. However, their origin and consequences are poorly understood. We performed molecular analysis of two patients with congenital disease who carried de novo genomic rearrangements. We found that the rearrangements in both patients hit genes that are recurrently rearranged in cancer (ETV1, FOXP1, and microRNA cluster C19MC) and drive formation of fusion genes similar to those described in cancer. Subsequent analysis of a large set of 552 de novo germline genomic rearrangements underlying congenital disorders revealed enrichment for genes rearranged in cancer and overlap with somatic cancer breakpoints. Breakpoints of common (inherited) germline structural variations also overlap with cancer breakpoints but are depleted for cancer genes. We propose that the same genomic positions are prone to genomic rearrangements in germline and soma but that timing and context of breakage determines whether developmental defects or cancer are promoted.
Keywords
GENE FUSIONS, STRUCTURAL VARIATION, REPAIR, ETV1, IDENTIFICATION, ABNORMALITIES, AUTISM SPECTRUM DISORDERS, DE-NOVO, COPY NUMBER VARIATION, PROSTATE-CANCER

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Citation

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MLA
van Heesch, Sebastiaan, Marieke Simonis, Markus J van Roosmalen, et al. “Genomic and Functional Overlap Between Somatic and Germline Chromosomal Rearrangements.” CELL REPORTS 9.6 (2014): 2001–2010. Print.
APA
van Heesch, S., Simonis, M., van Roosmalen, M. J., Pillalamarri, V., Brand, H., Kuijk, E. W., de Luca, K. L., et al. (2014). Genomic and functional overlap between somatic and germline chromosomal rearrangements. CELL REPORTS, 9(6), 2001–2010.
Chicago author-date
van Heesch, Sebastiaan, Marieke Simonis, Markus J van Roosmalen, Vamsee Pillalamarri, Harrison Brand, Ewart W Kuijk, Kim L de Luca, et al. 2014. “Genomic and Functional Overlap Between Somatic and Germline Chromosomal Rearrangements.” Cell Reports 9 (6): 2001–2010.
Chicago author-date (all authors)
van Heesch, Sebastiaan, Marieke Simonis, Markus J van Roosmalen, Vamsee Pillalamarri, Harrison Brand, Ewart W Kuijk, Kim L de Luca, Nico Lansu, A Koen Braat, Androniki Menelaou, Wensi Hao, Jeroen Korving, Simone Snijder, Lars T van der Veken, Ron Hochstenbach, Alida C Knegt, Karen Duran, Ivo Renkens, Najla Alekozai, Myrthe Jager, Sarah Vergult, Björn Menten, Ewart de Bruijn, Sander Boymans, Elly Ippel, Ellen van Binsbergen, Michael E Talkowski, Klaske Lichtenbelt, Edwin Cuppen, and Wigard P Kloosterman. 2014. “Genomic and Functional Overlap Between Somatic and Germline Chromosomal Rearrangements.” Cell Reports 9 (6): 2001–2010.
Vancouver
1.
van Heesch S, Simonis M, van Roosmalen MJ, Pillalamarri V, Brand H, Kuijk EW, et al. Genomic and functional overlap between somatic and germline chromosomal rearrangements. CELL REPORTS. 2014;9(6):2001–10.
IEEE
[1]
S. van Heesch et al., “Genomic and functional overlap between somatic and germline chromosomal rearrangements,” CELL REPORTS, vol. 9, no. 6, pp. 2001–2010, 2014.
@article{5827695,
  abstract     = {Genomic rearrangements are a common cause of human congenital abnormalities. However, their origin and consequences are poorly understood. We performed molecular analysis of two patients with congenital disease who carried de novo genomic rearrangements. We found that the rearrangements in both patients hit genes that are recurrently rearranged in cancer (ETV1, FOXP1, and microRNA cluster C19MC) and drive formation of fusion genes similar to those described in cancer. Subsequent analysis of a large set of 552 de novo germline genomic rearrangements underlying congenital disorders revealed enrichment for genes rearranged in cancer and overlap with somatic cancer breakpoints. Breakpoints of common (inherited) germline structural variations also overlap with cancer breakpoints but are depleted for cancer genes. We propose that the same genomic positions are prone to genomic rearrangements in germline and soma but that timing and context of breakage determines whether developmental defects or cancer are promoted.},
  author       = {van Heesch, Sebastiaan and Simonis, Marieke and van Roosmalen, Markus J and Pillalamarri, Vamsee and Brand, Harrison and Kuijk, Ewart W and de Luca, Kim L and Lansu, Nico and Braat, A Koen and Menelaou, Androniki and Hao, Wensi and Korving, Jeroen and Snijder, Simone and van der Veken, Lars T and Hochstenbach, Ron and Knegt, Alida C and Duran, Karen and Renkens, Ivo and Alekozai, Najla and Jager, Myrthe and Vergult, Sarah and Menten, Björn and de Bruijn, Ewart and Boymans, Sander and Ippel, Elly and van Binsbergen, Ellen and Talkowski, Michael E and Lichtenbelt, Klaske and Cuppen, Edwin and Kloosterman, Wigard P},
  issn         = {2211-1247},
  journal      = {CELL REPORTS},
  keywords     = {GENE FUSIONS,STRUCTURAL VARIATION,REPAIR,ETV1,IDENTIFICATION,ABNORMALITIES,AUTISM SPECTRUM DISORDERS,DE-NOVO,COPY NUMBER VARIATION,PROSTATE-CANCER},
  language     = {eng},
  number       = {6},
  pages        = {2001--2010},
  title        = {Genomic and functional overlap between somatic and germline chromosomal rearrangements},
  url          = {http://dx.doi.org/10.1016/j.celrep.2014.11.022},
  volume       = {9},
  year         = {2014},
}

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