Home > A. Molecular pathology > chromothripsis

chromothripsis

Wednesday 14 March 2012

Chromosome catastrophes

A variety of mutational mechanisms shape the dynamic architecture of human genomes and occasionally result in congenital defects and disease.

Cancer is driven by somatically acquired point mutations and chromosomal rearrangements, conventionally thought to accumulate gradually over time.

Using next-generation sequencing, it has been characterized a phenomenon, called "chromothripsis", whereby tens to hundreds of genomic rearrangements occur in a one-off cellular crisis.

Rearrangements involving one or a few chromosomes crisscross back and forth across involved regions, generating frequent oscillations between two copy number states.

These genomic hallmarks are highly improbable if rearrangements accumulate over time and instead imply that nearly all occur during a single cellular catastrophe.

The stamp of chromothripsis can be seen in at least 2%-3% of all cancers, across many subtypes, and is present in ∼25% of bone cancers.

One, or indeed more than one, cancer-causing lesion can emerge out of the genomic crisis.

This phenomenon has important implications for the origins of genomic remodeling and temporal emergence of cancer.

By tumoral types

- colorectal cancer

  • Chromothripsis is a prevalent mechanism driving structural rearrangements in colorectal cancer.
  • A complex interplay between point mutations, simple copy number changes and chromothripsis events drive colorectal tumor development and metastasis.

Open references

- Chromothripsis is a common mechanism driving genomic rearrangements in primary and metastatic colorectal cancer. Kloosterman WP, Hoogstraat M, Paling O, Tavakoli-Yaraki M, Renkens I, Vermaat JS, van Roosmalen MJ, van Lieshout S, Nijman IJ, Roessingh W, van ’t Slot R, van de Belt J, Guryev V, Koudijs M, Voest E, Cuppen E. Genome Biol. 2011 Oct 19;12(10):R103. doi: 10.1186/gb-2011-12-10-r103 . PMID: #22014273# [Free]

References

- Complex reorganization and predominant non-homologous repair following chromosomal breakage in karyotypically balanced germline rearrangements and transgenic integration. Chiang C, Jacobsen JC, Ernst C, Hanscom C, Heilbut A, Blumenthal I, Mills RE, Kirby A, Lindgren AM, Rudiger SR, McLaughlan CJ, Bawden CS, Reid SJ, Faull RL, Snell RG, Hall IM, Shen Y, Ohsumi TK, Borowsky ML, Daly MJ, Lee C, Morton CC, Macdonald ME, Gusella JF, Talkowski ME. Nat Genet. 2012 Mar 4. PMID: #22388000#

- Sequencing of neuroblastoma identifies chromothripsis and defects in neuritogenesis genes. Molenaar JJ, Koster J, Zwijnenburg DA, van Sluis P, Valentijn LJ, van der Ploeg I, Hamdi M, van Nes J, Westerman BA, van Arkel J, Ebus ME, Haneveld F, Lakeman A, Schild L, Molenaar P, Stroeken P, van Noesel MM, Ora I, Santo EE, Caron HN, Westerhout EM, Versteeg R. Nature. 2012 Feb 22. PMID: #22367537#

- Genome sequencing of pediatric medulloblastoma links catastrophic DNA rearrangements with TP53 mutations. Rausch T, Jones DT, Zapatka M, Stütz AM, Zichner T, Weischenfeldt J, Jäger N, Remke M, Shih D, Northcott PA, Pfaff E, Tica J, Wang Q, Massimi L, Witt H, Bender S, Pleier S, Cin H, Hawkins C, Beck C, von Deimling A, Hans V, Brors B, Eils R, Scheurlen W, Blake J, Benes V, Kulozik AE, Witt O, Martin D, Zhang C, Porat R, Merino DM, Wasserman J, Jabado N, Fontebasso A, Bullinger L, Rücker FG, Döhner K, Döhner H, Koster J, Molenaar JJ, Versteeg R, Kool M, Tabori U, Malkin D, Korshunov A, Taylor MD, Lichter P, Pfister SM, Korbel JO. Cell. 2012 Jan 20;148(1-2):59-71. PMID: #22265402#

- Chromothripsis and human disease: piecing together the shattering process. Maher CA, Wilson RK. Cell. 2012 Jan 20;148(1-2):29-32. PMID: #22265399#

- DNA breaks and chromosome pulverization from errors in mitosis. Crasta K, Ganem NJ, Dagher R, Lantermann AB, Ivanova EV, Pan Y, Nezi L, Protopopov A, Chowdhury D, Pellman D. Nature. 2012 Jan 18;482(7383):53-8. PMID: #22258507#

- Chromothripsis is a common mechanism driving genomic rearrangements in primary and metastatic colorectal cancer. Kloosterman WP, Hoogstraat M, Paling O, Tavakoli-Yaraki M, Renkens I, Vermaat JS, van Roosmalen MJ, van Lieshout S, Nijman IJ, Roessingh W, van ’t Slot R, van de Belt J, Guryev V, Koudijs M, Voest E, Cuppen E. Genome Biol. 2011 Oct 19;12(10):R103. PMID: #22014273#

- The consequences of structural genomic alterations in humans: Genomic Disorders, genomic instability and cancer. Colnaghi R, Carpenter G, Volker M, O’Driscoll M. Semin Cell Dev Biol. 2011 Oct;22(8):875-85. PMID: #21802523#

- Chromosome catastrophes involve replication mechanisms generating complex genomic rearrangements. Liu P, Erez A, Nagamani SC, Dhar SU, Kołodziejska KE, Dharmadhikari AV, Cooper ML, Wiszniewska J, Zhang F, Withers MA, Bacino CA, Campos-Acevedo LD, Delgado MR, Freedenberg D, Garnica A, Grebe TA, Hernández-Almaguer D, Immken L, Lalani SR, McLean SD, Northrup H, Scaglia F, Strathearn L, Trapane P, Kang SH, Patel A, Cheung SW, Hastings PJ, Stankiewicz P, Lupski JR, Bi W. Cell. 2011 Sep 16;146(6):889-903. PMID: #21925314#

- Chromothripsis identifies a rare and aggressive entity among newly diagnosed multiple myeloma patients. Magrangeas F, Avet-Loiseau H, Munshi NC, Minvielle S. Blood. 2011 Jul 21;118(3):675-8. Epub 2011 May 31. PMID: #21628407#

- Diverse system stresses: common mechanisms of chromosome fragmentation. Stevens JB, Abdallah BY, Liu G, Ye CJ, Horne SD, Wang G, Savasan S, Shekhar M, Krawetz SA, Hüttemann M, Tainsky MA, Wu GS, Xie Y, Zhang K, Heng HH. Cell Death Dis. 2011 Jun 30;2:e178. PMID: #21716293#

- Chromothripsis as a mechanism driving complex de novo structural rearrangements in the germline. Kloosterman WP, Guryev V, van Roosmalen M, Duran KJ, de Bruijn E, Bakker SC, Letteboer T, van Nesselrooij B, Hochstenbach R, Poot M, Cuppen E. Hum Mol Genet. 2011 May 15;20(10):1916-24. PMID: #21349919#

- Massive genomic rearrangement acquired in a single catastrophic event during cancer development. Stephens PJ, Greenman CD, Fu B, Yang F, Bignell GR, Mudie LJ, Pleasance ED, Lau KW, Beare D, Stebbings LA, McLaren S, Lin ML, McBride DJ, Varela I, Nik-Zainal S, Leroy C, Jia M, Menzies A, Butler AP, Teague JW, Quail MA, Burton J, Swerdlow H, Carter NP, Morsberger LA, Iacobuzio-Donahue C, Follows GA, Green AR, Flanagan AM, Stratton MR, Futreal PA, Campbell PJ. Cell. 2011 Jan 7;144(1):27-40. PMID: #21215367#

- Cancer genomes evolve by pulverizing single chromosomes. Meyerson M, Pellman D. Cell. 2011 Jan 7;144(1):9-10. PMID: #21215363#

Chromothripsis