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Title:
Genome remodelling in a basal-like breast cancer metastasis and xenograft | Nature
Description:
Massively parallel DNA sequencing technologies provide an unprecedented ability to screen entire genomes for genetic changes associated with tumour progression. Here we describe the genomic analyses of four DNA samples from an African-American patient with basal-like breast cancer: peripheral blood, the primary tumour, a brain metastasis and a xenograft derived from the primary tumour. The metastasis contained two de novo mutations and a large deletion not present in the primary tumour, and was significantly enriched for 20 shared mutations. The xenograft retained all primary tumour mutations and displayed a mutation enrichment pattern that resembled the metastasis. Two overlapping large deletions, encompassing CTNNA1, were present in all three tumour samples. The differential mutation frequencies and structural variation patterns in metastasis and xenograft compared with the primary tumour indicate that secondary tumours may arise from a minority of cells within the primary tumour. With the latest DNA sequencing technologies it is now possible to screen an entire genome for the genetic changes associated with tumour progression. This approach has been used to obtain complete sequences of four DNA samples from a 44-year-old African-American patient with basal-like breast cancer: the primary tumour, peripheral blood, a brain metastasis and a first-passage xenograft derived from the primary tumour. Mutational analysis suggests that the metastasis tumour specifically selects a subset of cells from the primary tumour that contain pre-existing mutations, and also develops a small number of de novo mutations. Massively parallel DNA sequencing allows entire genomes to be screened for genetic changes associated with tumour progression. Here, the genomes of four DNA samples from a 44-year-old African-American patient with basal-like breast cancer were analysed. The samples came from peripheral blood, the primary tumour, a brain metastasis and a xenograft derived from the primary tumour. The findings indicate that cells with a distinct subset of the primary tumour mutation might be selected during metastasis and xenografting.
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headline:Genome remodelling in a basal-like breast cancer metastasis and xenograft
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headline:Genome remodelling in a basal-like breast cancer metastasis and xenograft
description:Massively parallel DNA sequencing technologies provide an unprecedented ability to screen entire genomes for genetic changes associated with tumour progression. Here we describe the genomic analyses of four DNA samples from an African-American patient with basal-like breast cancer: peripheral blood, the primary tumour, a brain metastasis and a xenograft derived from the primary tumour. The metastasis contained two de novo mutations and a large deletion not present in the primary tumour, and was significantly enriched for 20 shared mutations. The xenograft retained all primary tumour mutations and displayed a mutation enrichment pattern that resembled the metastasis. Two overlapping large deletions, encompassing CTNNA1, were present in all three tumour samples. The differential mutation frequencies and structural variation patterns in metastasis and xenograft compared with the primary tumour indicate that secondary tumours may arise from a minority of cells within the primary tumour. With the latest DNA sequencing technologies it is now possible to screen an entire genome for the genetic changes associated with tumour progression. This approach has been used to obtain complete sequences of four DNA samples from a 44-year-old African-American patient with basal-like breast cancer: the primary tumour, peripheral blood, a brain metastasis and a first-passage xenograft derived from the primary tumour. Mutational analysis suggests that the metastasis tumour specifically selects a subset of cells from the primary tumour that contain pre-existing mutations, and also develops a small number of de novo mutations. Massively parallel DNA sequencing allows entire genomes to be screened for genetic changes associated with tumour progression. Here, the genomes of four DNA samples from a 44-year-old African-American patient with basal-like breast cancer were analysed. The samples came from peripheral blood, the primary tumour, a brain metastasis and a xenograft derived from the primary tumour. The findings indicate that cells with a distinct subset of the primary tumour mutation might be selected during metastasis and xenografting.
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name:Ling Lin
affiliation:
name:The Genome Center at Washington University,
address:
name:The Genome Center at Washington University,,
type:PostalAddress
type:Organization
name:Michael C. Wendl
affiliation:
name:The Genome Center at Washington University,
address:
name:The Genome Center at Washington University,,
type:PostalAddress
type:Organization
name:Department of Genetics,
address:
name:Department of Genetics,,
type:PostalAddress
type:Organization
name:Joshua F. McMichael
affiliation:
name:The Genome Center at Washington University,
address:
name:The Genome Center at Washington University,,
type:PostalAddress
type:Organization
name:Vincent J. Magrini
affiliation:
name:The Genome Center at Washington University,
address:
name:The Genome Center at Washington University,,
type:PostalAddress
type:Organization
name:Department of Genetics,
address:
name:Department of Genetics,,
type:PostalAddress
type:Organization
name:Lisa Cook
affiliation:
name:The Genome Center at Washington University,
address:
name:The Genome Center at Washington University,,
type:PostalAddress
type:Organization
name:Sean D. McGrath
affiliation:
name:The Genome Center at Washington University,
address:
name:The Genome Center at Washington University,,
type:PostalAddress
type:Organization
name:Tammi L. Vickery
affiliation:
name:The Genome Center at Washington University,
address:
name:The Genome Center at Washington University,,
type:PostalAddress
type:Organization
name:Elizabeth Appelbaum
affiliation:
name:The Genome Center at Washington University,
address:
name:The Genome Center at Washington University,,
type:PostalAddress
type:Organization
name:Katherine DeSchryver
affiliation:
name:Department of Medicine,
address:
name:Department of Medicine,,
type:PostalAddress
type:Organization
name:Sherri Davies
affiliation:
name:Department of Medicine,
address:
name:Department of Medicine,,
type:PostalAddress
type:Organization
name:Therese Guintoli
affiliation:
name:Department of Medicine,
address:
name:Department of Medicine,,
type:PostalAddress
type:Organization
name:Li Lin
affiliation:
name:Department of Medicine,
address:
name:Department of Medicine,,
type:PostalAddress
type:Organization
name:Robert Crowder
affiliation:
name:Department of Medicine,
address:
name:Department of Medicine,,
type:PostalAddress
type:Organization
name:Yu Tao
affiliation:
name:Division of Biostatistics,
address:
name:Division of Biostatistics,,
type:PostalAddress
type:Organization
name:Jacqueline E. Snider
affiliation:
name:Department of Medicine,
address:
name:Department of Medicine,,
type:PostalAddress
type:Organization
name:Scott M. Smith
affiliation:
name:The Genome Center at Washington University,
address:
name:The Genome Center at Washington University,,
type:PostalAddress
type:Organization
name:Adam F. Dukes
affiliation:
name:The Genome Center at Washington University,
address:
name:The Genome Center at Washington University,,
type:PostalAddress
type:Organization
name:Gabriel E. Sanderson
affiliation:
name:The Genome Center at Washington University,
address:
name:The Genome Center at Washington University,,
type:PostalAddress
type:Organization
name:Craig S. Pohl
affiliation:
name:The Genome Center at Washington University,
address:
name:The Genome Center at Washington University,,
type:PostalAddress
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name:Kim D. Delehaunty
affiliation:
name:The Genome Center at Washington University,
address:
name:The Genome Center at Washington University,,
type:PostalAddress
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name:Catrina C. Fronick
affiliation:
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address:
name:The Genome Center at Washington University,,
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address:
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affiliation:
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address:
name:The Genome Center at Washington University,,
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affiliation:
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address:
name:The Genome Center at Washington University,,
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affiliation:
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address:
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name:William Schierding
affiliation:
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address:
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affiliation:
name:The Genome Center at Washington University,
address:
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affiliation:
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address:
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affiliation:
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address:
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affiliation:
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address:
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affiliation:
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address:
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address:
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affiliation:
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address:
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affiliation:
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address:
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affiliation:
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address:
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affiliation:
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address:
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affiliation:
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address:
name:The Genome Center at Washington University,,
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address:
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affiliation:
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address:
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affiliation:
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address:
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type:PostalAddress
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address:
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type:PostalAddress
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affiliation:
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address:
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address:
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type:PostalAddress
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address:
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type:PostalAddress
type:Organization
name:George M. Weinstock
affiliation:
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address:
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type:PostalAddress
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name:Department of Genetics,
address:
name:Department of Genetics,,
type:PostalAddress
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address:
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type:PostalAddress
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name:Mark Watson
affiliation:
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address:
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affiliation:
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address:
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address:
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email:[email protected]
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address:
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name:The Genome Center at Washington University,,
name:The Genome Center at Washington University,,
name:Department of Genetics,,
name:The Genome Center at Washington University,,
name:The Genome Center at Washington University,,
name:The Genome Center at Washington University,,
name:Department of Genetics,,
name:The Genome Center at Washington University,,
name:Department of Genetics,,
name:The Genome Center at Washington University,,
name:Department of Medicine,,
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name:Department of Genetics,,
name:The Genome Center at Washington University,,
name:The Genome Center at Washington University,,
name:The Genome Center at Washington University,,
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name:The Genome Center at Washington University,,
name:The Genome Center at Washington University,,
name:The Genome Center at Washington University,,
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name:The Genome Center at Washington University,,
name:Department of Genetics,,
name:The Genome Center at Washington University,,
name:The Genome Center at Washington University,,
name:The Genome Center at Washington University,,
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name:Department of Medicine,,
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name:The Genome Center at Washington University,,
name:The Genome Center at Washington University,,
name:The Genome Center at Washington University,,
name:The Genome Center at Washington University,,
name:The Genome Center at Washington University,,
name:The Genome Center at Washington University,,
name:The Genome Center at Washington University,,
name:The Genome Center at Washington University,,
name:The Genome Center at Washington University,,
name:The Genome Center at Washington University,,
name:The Genome Center at Washington University,,
name:The Genome Center at Washington University,,
name:The Genome Center at Washington University,,
name:The Genome Center at Washington University,,
name:The Genome Center at Washington University,,
name:The Genome Center at Washington University,,
name:The Genome Center at Washington University,,
name:The Genome Center at Washington University,,
name:The Genome Center at Washington University,,
name:The Genome Center at Washington University,,
name:The Genome Center at Washington University,,
name:The Genome Center at Washington University,,
name:The Genome Center at Washington University,,
name:The Genome Center at Washington University,,
name:The Genome Center at Washington University,,
name:Department of Surgery and the Young Womenâs Breast Cancer Program,,
name:Department of Surgery and the Young Womenâs Breast Cancer Program,,
name:Department of Surgery and the Young Womenâs Breast Cancer Program,,
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