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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)

Bottom Line: 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.We find that one, or indeed more than one, cancer-causing lesion can emerge out of the genomic crisis.

View Article: PubMed Central - PubMed

Affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.

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Spectral Karyotypes for (A) 8505C and (B) SNU-C1, Related to Figure 3
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figs3: Spectral Karyotypes for (A) 8505C and (B) SNU-C1, Related to Figure 3

Mentions: One question that arises is whether the rearrangements are all found on a single parental copy of the chromosome or whether both copies are involved. We therefore performed spectral karyotyping on the three cell lines (Figure 3A and Figure S3). TK10, a hyperdiploid line, carries six copies of chromosome 5. Consistent with the observed copy number profile alternating between states of copy number 4 with LOH and copy number 6 with heterozygosity, the karyotype showed four grossly normal copies of chromosome 5 and two smaller derivative chromosomes. Similarly, in 8505C, two copies of chromosome 9 showed distinctly foreshortened p arms alongside two cytogenetically normal chromosomes. None of the three karyotypes indicated translocations involving the respective derivative chromosomes, confirming the impression from the paired-end sequencing data that the genomic remodeling of these regions was entirely intrachromosomal. Cytogenetic changes were consistently seen across all cells examined.


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)

Spectral Karyotypes for (A) 8505C and (B) SNU-C1, Related to Figure 3
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3065307&req=5

figs3: Spectral Karyotypes for (A) 8505C and (B) SNU-C1, Related to Figure 3
Mentions: One question that arises is whether the rearrangements are all found on a single parental copy of the chromosome or whether both copies are involved. We therefore performed spectral karyotyping on the three cell lines (Figure 3A and Figure S3). TK10, a hyperdiploid line, carries six copies of chromosome 5. Consistent with the observed copy number profile alternating between states of copy number 4 with LOH and copy number 6 with heterozygosity, the karyotype showed four grossly normal copies of chromosome 5 and two smaller derivative chromosomes. Similarly, in 8505C, two copies of chromosome 9 showed distinctly foreshortened p arms alongside two cytogenetically normal chromosomes. None of the three karyotypes indicated translocations involving the respective derivative chromosomes, confirming the impression from the paired-end sequencing data that the genomic remodeling of these regions was entirely intrachromosomal. Cytogenetic changes were consistently seen across all cells examined.

Bottom Line: 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.We find that one, or indeed more than one, cancer-causing lesion can emerge out of the genomic crisis.

View Article: PubMed Central - PubMed

Affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.

Show MeSH
Related in: MedlinePlus