Abstract
The discovery of a new class of massive chromosomal rearrangement, baptized chromothripsis, in different cancers and congenital disorders has deeply modified our understanding on the genesis of complex genomic rearrangements. Several mechanisms, involving abortive apoptosis, telomere erosion, mitotic errors, micronuclei formation, and p53 inactivation, might cause chromothripsis. The remarkable point is that all these plausible mechanisms have been identified in the field of human reproduction as causal factors for reproductive failures and chromosomal abnormality genesis. Specific features of gametogenesis and early embryonic development may contribute to the emergence of chromothripsis. Multiple lines of evidence support the assumption that chromothripsis may arise more frequently than previously thought in both gametogenesis and early human embryogenesis.
Key words
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Stephens PJ, Greenman CD, Fu B et al (2011) Massive genomic rearrangement acquired in a single catastrophic event during cancer development. Cell 144:27–40
Magrangeas F, Avet-Loiseau H, Munshi NC et al (2011) Chromothripsis identifies a rare and aggressive entity among newly diagnosed multiple myeloma patients. Blood 118:675–678
Rode A, Maass KK, Willmund KV et al (2016) Chromothripsis in cancer cells: an update. Int J Cancer 138:2322–2333
Kloosterman WP, Gurvey V, van Roosmalen M et al (2011) Chromothripsis as a mechanism driving complex de novo structural rearrangements in the germline. Hum Mol Genet 20:1916–1924
Chiang C, Jacobsen JC, Ernst C et al (2012) Complex reorganization and predominant non-homologous repair following chromosomal breakage in karyotypically balanced germline rearrangements and transgenic integration. Nat Genet 44:390–998
De Pagter MS, van Roosmalen MJ, Baas AF et al (2015) Chromothripsis in healthy individuals affects multiple protein-coding genes and can result in severe congenital abnormalities in offspring. Am J Hum Genet 96:651–656
Tubio JMC, Estivill X (2011) When catastrophe strikes a cell. Nature 470:476–477
Crasta K, Ganem NJ, Dagher R et al (2012) DNA breaks and chromosome pulverization from errors in mitosis. Nature 482:53–58
Zhang CZ, Spektor A, Cornils H et al (2015) Chromothripsis from DNA damage in micronuclei. Nature 522:179–184
Mardin BR, Drainas AP, Waszak SM et al (2015) A cell-based model system links chromothripsis with hyperploidy. Mol Syst Biol 11:828. https://doi.org/10.15252/msb.20156505
Maciejowski j LY, Bosco N et al (2015) Chromothripsis and Kataegis induced by telomere crisis. Cell 163:1641–1654
Pellestor F, Gatinois V, Puechberty J et al (2014) Chromothripsis: potential origin in gametogenesis and preimplantation cell divisions. A review. Fertil Steril 102:1785–1796
Daughtry BL, Chavez SL (2016) Chromosomal instability in mammalian pre-implantation embryos: potential causes, detection methods, and clinical consequences. Cell Tissue Res 363:201–225
Pellestor F (2014) Chromothripsis: how does such a catastrophic event impact human reproduction ? Hum Reprod 29:388–393
Fukami M, Shima H, Suzuki E et al (2017) Catastrophic cellular events leading to complex chromosomal rearrangements in the germline. Clin Genet 91:653–660
Rausch T, Jones DTW, Zapatka M et al (2012) Genome sequencing of pediatric medulloblastoma links catastrophic DNA rearrangements with TP53 mutations. Cell 148:59–71
Ivkov R, Bunz F (2015) Pathways to chromothripsis. Cell Cycle 14:2886–2890
Korbel JO, Campbell PJ (2013) Criteria for inference of chromothripsis in cancer genomes. Cell 152:1226–1236
Kloosterman WP, Cuppen E (2013) Chromothripsis in congenital disorders and cancer: similarities and differences. Curr Opin Cell Biol 25:341–348
Yang J, Liu J, Ouyang L et al (2016) CTLP scanner: a web server for chromothripsis-like pattern detection. Nucleic Acids Res 44(W1):W252–W258. https://doi.org/10.1093/nar/gkw434
Kloosterman WP, Tavakoli-Yaraki M, van Roosmalen M et al (2012) Constitutional chromothripsis rearrangements involve clustered double-stranded DNA breaks and nonhomologous repair mechanisms. Cell Rep 1:648–655
Macera MJ, Sobrino A, Levy B et al (2015) Prenatal diagnosis of chromothripsis, with nine breaks characterized by karyotyping, FISH, microarray and whole-genome sequencing. Prenat Diagn 35:299–301
Bertelsen B, Nazaryan-Petersen L, Sun W et al (2016) A germline chromothripsis event stably segregating in 11 individuals through three generations. Genet Med 15:494–500
Anderson SE, Kamath A, Pilz DT et al (2016) A rare example of germ-line chromothripsis resulting in large genomic imbalance. Clin Dysmorphol 25:58–62
Sakkas D, Alvarez JG (2010) Sperm DNA fragmentation: mechanisms of origin, impact on reproductive outcome, and analysis. Fertil Steril 93:1027–1036
Taylor RC, Cullen SP, Martin SJ (2008) Apoptosis: controlled demolition at the cellular level. Nat Rev Mol Cell Biol 9:231–241
Tang HL, Tang HM, Mak KH et al (2012) Cell survival, DNA damage, and oncogenic transformation after a transient and reversible apoptotic response. Mol Biol Cell 23:2240–2252
Sakkas D, Seli E, Bizzaro D et al (2003) Abnormal spermatozoa in the ejaculate: abortive apoptosis and faulty nuclear remodeling during spermatogenesis. Reprod Biomed Online 7:428–432
Jones MJK, Jallepalli PV (2012) Chromothripsis: chromosomes in crisis. Dev Cell 23:908–917
Delhanty JDA, Pellestor F (eds) (2011) Aneuploidy. Cytogenet Genome Res 133:2–4
Baarends WM, van der Laan R, Grootegoed A (2001) DNA repair mechanisms and gametogenesis. Reproduction 121:31–39
Oliver-Bonnet M, Ko E, Martin RH (2005) Male infertility in reciprocal translocation carriers: the sex body affair. Cytogenet Genome Res 111:434–346
Martin RH (2008) Cytogenetic determinants of male fertility. Hum Reprod Update 14:379–390
Aoki VW, Liu L, Carrell DT (2005) Identification and evaluation of a novel sperm protamine abnormality in a population of infertile males. Hum Reprod 20:1298–1306
Oliva R (2006) Protamines and male infertility. Hum Reprod Update 12:417–435
Carroll J, Marangos P (2013) The DNA damage response in mammalian oocytes. Front Genet 4:1–9
Hunt PA, Hassold TJ (2008) Human female meiosis: what makes a good egg go bad? Trends Genet 24:86–93
Marchetti F, Essers J, Kanaar R et al (2007) Disruption of maternal DNA repair increases sperm-derived chromosomal aberrations. Proc Natl Acad Sci U S A 104:17725–17729
Jaroudi S, Kakourou G, Cawood S et al (2009) Expression profiling of DNA repair genes in human oocytes and blastocysts using microarrays. Hum Reprod 24:2649–2655
Steuerwald N (2005) Meiotic spindle checkpoints for assessment of aneuploid oocytes. Cytogenet Genome Res 111:256–259
Kastan MB, Lim DS (2000) The many substrates and functions of ATM. Nat Rev Mol Cell Biol 1:179–186
Pellestor F, Anahory T, Hamamah S (2005) The chromosomal analysis of human oocytes. An overview of established procedures. Hum Reprod Update 11:15–32
McLay DW, Clarke HJ (2003) Remodeling the paternal chromatin at fertilization in mammals. Reproduction 125:625–633
Ahmadi A, Ng SC (1999) Developmental capacity of damaged spermatozoa. Hum Reprod 14:2279–2285
Eichenlaub-Ritter U, Schmiady H, Kentenich H et al (1995) Recurrent failure in polar body formation and premature chromosome condensation in oocytes from a human patient: indicators of asynchrony in nuclear and cytoplasmic maturation. Hum Reprod 10:2343–2349
Meyerson M, Pellman D (2011) Cancer genomes evolve by pulverizing single chromosome. Cell 144:9–10
Lebedev I (2011) Mosaic aneuploidy in early fetal losses. Cytogenet Genome Res 133:169–183
Acknowledgments
Work in the unit of Chromosomal Genetics is supported by the CHU research platform ChromoStem (http://www.chu-montpellier.fr/fr/chercheurs/plateformes/les-plateformes-recherche/chromostem/).
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2018 Springer Science+Business Media, LLC, part of Springer Nature
About this protocol
Cite this protocol
Pellestor, F., Gatinois, V. (2018). Potential Role of Chromothripsis in the Genesis of Complex Chromosomal Rearrangements in Human Gametes and Preimplantation Embryo. In: Pellestor, F. (eds) Chromothripsis. Methods in Molecular Biology, vol 1769. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7780-2_3
Download citation
DOI: https://doi.org/10.1007/978-1-4939-7780-2_3
Published:
Publisher Name: Humana Press, New York, NY
Print ISBN: 978-1-4939-7779-6
Online ISBN: 978-1-4939-7780-2
eBook Packages: Springer Protocols