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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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Related in: MedlinePlus

Rearrangement Screens in Three Cancer Cell Lines Showing Evidence for ChromothripsisCopy number profiles derive from SNP6 microarray data and are shown as the upper panel of points for each cell line. Allelic ratios for each SNP are shown in the lower panel of dots: homozygous SNPs cluster at allelic ratios near 0 or 1, heterozygous SNPs cluster around 0.5. Intrachromosomal rearrangements of all four possible orientations are shown, with deletion-type events as blue lines, tandem duplication-type in red, tail-to-tail inverted rearrangements in green and head-to-head inverted rearrangements in yellow.(A) SNU-C1, a cell line from a colorectal cancer, carries 239 rearrangements involving chromosome 15.(B) 8505C, a thyroid cancer cell line, has 77 rearrangements involving chromosome 9p.(C) TK10, a renal cancer cell line, has 55 rearrangements involving chromosome 5.
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fig2: Rearrangement Screens in Three Cancer Cell Lines Showing Evidence for ChromothripsisCopy number profiles derive from SNP6 microarray data and are shown as the upper panel of points for each cell line. Allelic ratios for each SNP are shown in the lower panel of dots: homozygous SNPs cluster at allelic ratios near 0 or 1, heterozygous SNPs cluster around 0.5. Intrachromosomal rearrangements of all four possible orientations are shown, with deletion-type events as blue lines, tandem duplication-type in red, tail-to-tail inverted rearrangements in green and head-to-head inverted rearrangements in yellow.(A) SNU-C1, a cell line from a colorectal cancer, carries 239 rearrangements involving chromosome 15.(B) 8505C, a thyroid cancer cell line, has 77 rearrangements involving chromosome 9p.(C) TK10, a renal cancer cell line, has 55 rearrangements involving chromosome 5.

Mentions: We selected four of these cell lines for further genomic analysis with massively parallel paired-end sequencing for rearrangements and cytogenetic studies: SNU-C1, 8505C, TK10, and SCLC-21H (described later). In SNU-C1, derived from a colorectal cancer, we identified 239 rearrangements involving chromosome 15 (Figure 2A and Table S2). From 8505C, a thyroid cancer line, we mapped 77 rearrangements involving the short arm of chromosome 9 (Figure 2B and Table S2), and for TK10, a renal cancer, 55 rearrangements involving chromosome 5 (Figure 2C and Table S2).


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)

Rearrangement Screens in Three Cancer Cell Lines Showing Evidence for ChromothripsisCopy number profiles derive from SNP6 microarray data and are shown as the upper panel of points for each cell line. Allelic ratios for each SNP are shown in the lower panel of dots: homozygous SNPs cluster at allelic ratios near 0 or 1, heterozygous SNPs cluster around 0.5. Intrachromosomal rearrangements of all four possible orientations are shown, with deletion-type events as blue lines, tandem duplication-type in red, tail-to-tail inverted rearrangements in green and head-to-head inverted rearrangements in yellow.(A) SNU-C1, a cell line from a colorectal cancer, carries 239 rearrangements involving chromosome 15.(B) 8505C, a thyroid cancer cell line, has 77 rearrangements involving chromosome 9p.(C) TK10, a renal cancer cell line, has 55 rearrangements involving chromosome 5.
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Related In: Results  -  Collection

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

fig2: Rearrangement Screens in Three Cancer Cell Lines Showing Evidence for ChromothripsisCopy number profiles derive from SNP6 microarray data and are shown as the upper panel of points for each cell line. Allelic ratios for each SNP are shown in the lower panel of dots: homozygous SNPs cluster at allelic ratios near 0 or 1, heterozygous SNPs cluster around 0.5. Intrachromosomal rearrangements of all four possible orientations are shown, with deletion-type events as blue lines, tandem duplication-type in red, tail-to-tail inverted rearrangements in green and head-to-head inverted rearrangements in yellow.(A) SNU-C1, a cell line from a colorectal cancer, carries 239 rearrangements involving chromosome 15.(B) 8505C, a thyroid cancer cell line, has 77 rearrangements involving chromosome 9p.(C) TK10, a renal cancer cell line, has 55 rearrangements involving chromosome 5.
Mentions: We selected four of these cell lines for further genomic analysis with massively parallel paired-end sequencing for rearrangements and cytogenetic studies: SNU-C1, 8505C, TK10, and SCLC-21H (described later). In SNU-C1, derived from a colorectal cancer, we identified 239 rearrangements involving chromosome 15 (Figure 2A and Table S2). From 8505C, a thyroid cancer line, we mapped 77 rearrangements involving the short arm of chromosome 9 (Figure 2B and Table S2), and for TK10, a renal cancer, 55 rearrangements involving chromosome 5 (Figure 2C and Table S2).

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