Comprehensive genome sequence analysis of a breast cancer amplicon

Colin Collins, Stanislav Volik, David Kowbel, David Ginzinger, Bauke Ylstra, Thomas Cloutier, Trevor Hawkins, Paul Predki, Christopher Martin, Meredith Wernick, Wen Lin Kuo, Arthur Alberts, Joe Gray

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

Gene amplification occurs in most solid tumors and is associated with poor prognosis. Amplification of 20q13.2 is common to several tumor types including breast cancer. The 1 Mb of sequence spanning the 20q13.2 breast cancer amplicon is one of the most exhaustively studied segments of the human genome. These studies have included amplicon mapping by comparative genomic hybridization (CGH), fluorescent in-situ hybridization (FISH), array-CGH, quantitative microsatellite analysis (QUMA), and functional genomic studies. Together these studies revealed a complex amplicon structure suggesting the presence of at least two driver genes in some tumors. One of these, ZNF217, is capable of immortalizing human mammary epithelial cells (HMEC) when overexpressed. In addition, we now report the sequencing of this region in human and mouse, and on quantitative expression studies in tumors. Amplicon localization now is straightforward and the availability of human and mouse genomic sequence facilitates their functional analysis. However, comprehensive annotation of megabase-scale regions requires integration of vast amounts of information. We present a system for integrative analysis and demonstrate its utility on 1.2 Mb of sequence spanning the 20q13.2 breast cancer amplicon and 865 kb of syntenic murine sequence. We integrate tumor genome copy number measurements with exhaustive genome landscape mapping, showing that amplicon boundaries are associated with maxima in repetitive element density and a region of evolutionary instability. This integration of comprehensive sequence annotation, quantitative expression analysis, and tumor amplicon boundaries provide evidence for an additional driver gene prefoldin 4 (PFDN4), coregulated genes, conserved noncoding regions, and associate repetitive elements with regions of genomic instability at this locus.

Original languageEnglish (US)
Pages (from-to)1034-1042
Number of pages9
JournalGenome Research
Volume11
Issue number6
DOIs
StatePublished - 2001
Externally publishedYes

Fingerprint

Sequence Analysis
Genome
Breast Neoplasms
Neoplasms
Comparative Genomic Hybridization
Genes
Gene Amplification
Genomic Instability
Nucleic Acid Repetitive Sequences
Chromosome Mapping
Human Genome
Fluorescence In Situ Hybridization
Microsatellite Repeats
In Situ Hybridization
Breast
Epithelial Cells

ASJC Scopus subject areas

  • Genetics

Cite this

Collins, C., Volik, S., Kowbel, D., Ginzinger, D., Ylstra, B., Cloutier, T., ... Gray, J. (2001). Comprehensive genome sequence analysis of a breast cancer amplicon. Genome Research, 11(6), 1034-1042. https://doi.org/10.1101/gr.GR1743R

Comprehensive genome sequence analysis of a breast cancer amplicon. / Collins, Colin; Volik, Stanislav; Kowbel, David; Ginzinger, David; Ylstra, Bauke; Cloutier, Thomas; Hawkins, Trevor; Predki, Paul; Martin, Christopher; Wernick, Meredith; Kuo, Wen Lin; Alberts, Arthur; Gray, Joe.

In: Genome Research, Vol. 11, No. 6, 2001, p. 1034-1042.

Research output: Contribution to journalArticle

Collins, C, Volik, S, Kowbel, D, Ginzinger, D, Ylstra, B, Cloutier, T, Hawkins, T, Predki, P, Martin, C, Wernick, M, Kuo, WL, Alberts, A & Gray, J 2001, 'Comprehensive genome sequence analysis of a breast cancer amplicon', Genome Research, vol. 11, no. 6, pp. 1034-1042. https://doi.org/10.1101/gr.GR1743R
Collins C, Volik S, Kowbel D, Ginzinger D, Ylstra B, Cloutier T et al. Comprehensive genome sequence analysis of a breast cancer amplicon. Genome Research. 2001;11(6):1034-1042. https://doi.org/10.1101/gr.GR1743R
Collins, Colin ; Volik, Stanislav ; Kowbel, David ; Ginzinger, David ; Ylstra, Bauke ; Cloutier, Thomas ; Hawkins, Trevor ; Predki, Paul ; Martin, Christopher ; Wernick, Meredith ; Kuo, Wen Lin ; Alberts, Arthur ; Gray, Joe. / Comprehensive genome sequence analysis of a breast cancer amplicon. In: Genome Research. 2001 ; Vol. 11, No. 6. pp. 1034-1042.
@article{c794ed96f6ee43edbd645d1229146181,
title = "Comprehensive genome sequence analysis of a breast cancer amplicon",
abstract = "Gene amplification occurs in most solid tumors and is associated with poor prognosis. Amplification of 20q13.2 is common to several tumor types including breast cancer. The 1 Mb of sequence spanning the 20q13.2 breast cancer amplicon is one of the most exhaustively studied segments of the human genome. These studies have included amplicon mapping by comparative genomic hybridization (CGH), fluorescent in-situ hybridization (FISH), array-CGH, quantitative microsatellite analysis (QUMA), and functional genomic studies. Together these studies revealed a complex amplicon structure suggesting the presence of at least two driver genes in some tumors. One of these, ZNF217, is capable of immortalizing human mammary epithelial cells (HMEC) when overexpressed. In addition, we now report the sequencing of this region in human and mouse, and on quantitative expression studies in tumors. Amplicon localization now is straightforward and the availability of human and mouse genomic sequence facilitates their functional analysis. However, comprehensive annotation of megabase-scale regions requires integration of vast amounts of information. We present a system for integrative analysis and demonstrate its utility on 1.2 Mb of sequence spanning the 20q13.2 breast cancer amplicon and 865 kb of syntenic murine sequence. We integrate tumor genome copy number measurements with exhaustive genome landscape mapping, showing that amplicon boundaries are associated with maxima in repetitive element density and a region of evolutionary instability. This integration of comprehensive sequence annotation, quantitative expression analysis, and tumor amplicon boundaries provide evidence for an additional driver gene prefoldin 4 (PFDN4), coregulated genes, conserved noncoding regions, and associate repetitive elements with regions of genomic instability at this locus.",
author = "Colin Collins and Stanislav Volik and David Kowbel and David Ginzinger and Bauke Ylstra and Thomas Cloutier and Trevor Hawkins and Paul Predki and Christopher Martin and Meredith Wernick and Kuo, {Wen Lin} and Arthur Alberts and Joe Gray",
year = "2001",
doi = "10.1101/gr.GR1743R",
language = "English (US)",
volume = "11",
pages = "1034--1042",
journal = "PCR Methods and Applications",
issn = "1088-9051",
publisher = "Cold Spring Harbor Laboratory Press",
number = "6",

}

TY - JOUR

T1 - Comprehensive genome sequence analysis of a breast cancer amplicon

AU - Collins, Colin

AU - Volik, Stanislav

AU - Kowbel, David

AU - Ginzinger, David

AU - Ylstra, Bauke

AU - Cloutier, Thomas

AU - Hawkins, Trevor

AU - Predki, Paul

AU - Martin, Christopher

AU - Wernick, Meredith

AU - Kuo, Wen Lin

AU - Alberts, Arthur

AU - Gray, Joe

PY - 2001

Y1 - 2001

N2 - Gene amplification occurs in most solid tumors and is associated with poor prognosis. Amplification of 20q13.2 is common to several tumor types including breast cancer. The 1 Mb of sequence spanning the 20q13.2 breast cancer amplicon is one of the most exhaustively studied segments of the human genome. These studies have included amplicon mapping by comparative genomic hybridization (CGH), fluorescent in-situ hybridization (FISH), array-CGH, quantitative microsatellite analysis (QUMA), and functional genomic studies. Together these studies revealed a complex amplicon structure suggesting the presence of at least two driver genes in some tumors. One of these, ZNF217, is capable of immortalizing human mammary epithelial cells (HMEC) when overexpressed. In addition, we now report the sequencing of this region in human and mouse, and on quantitative expression studies in tumors. Amplicon localization now is straightforward and the availability of human and mouse genomic sequence facilitates their functional analysis. However, comprehensive annotation of megabase-scale regions requires integration of vast amounts of information. We present a system for integrative analysis and demonstrate its utility on 1.2 Mb of sequence spanning the 20q13.2 breast cancer amplicon and 865 kb of syntenic murine sequence. We integrate tumor genome copy number measurements with exhaustive genome landscape mapping, showing that amplicon boundaries are associated with maxima in repetitive element density and a region of evolutionary instability. This integration of comprehensive sequence annotation, quantitative expression analysis, and tumor amplicon boundaries provide evidence for an additional driver gene prefoldin 4 (PFDN4), coregulated genes, conserved noncoding regions, and associate repetitive elements with regions of genomic instability at this locus.

AB - Gene amplification occurs in most solid tumors and is associated with poor prognosis. Amplification of 20q13.2 is common to several tumor types including breast cancer. The 1 Mb of sequence spanning the 20q13.2 breast cancer amplicon is one of the most exhaustively studied segments of the human genome. These studies have included amplicon mapping by comparative genomic hybridization (CGH), fluorescent in-situ hybridization (FISH), array-CGH, quantitative microsatellite analysis (QUMA), and functional genomic studies. Together these studies revealed a complex amplicon structure suggesting the presence of at least two driver genes in some tumors. One of these, ZNF217, is capable of immortalizing human mammary epithelial cells (HMEC) when overexpressed. In addition, we now report the sequencing of this region in human and mouse, and on quantitative expression studies in tumors. Amplicon localization now is straightforward and the availability of human and mouse genomic sequence facilitates their functional analysis. However, comprehensive annotation of megabase-scale regions requires integration of vast amounts of information. We present a system for integrative analysis and demonstrate its utility on 1.2 Mb of sequence spanning the 20q13.2 breast cancer amplicon and 865 kb of syntenic murine sequence. We integrate tumor genome copy number measurements with exhaustive genome landscape mapping, showing that amplicon boundaries are associated with maxima in repetitive element density and a region of evolutionary instability. This integration of comprehensive sequence annotation, quantitative expression analysis, and tumor amplicon boundaries provide evidence for an additional driver gene prefoldin 4 (PFDN4), coregulated genes, conserved noncoding regions, and associate repetitive elements with regions of genomic instability at this locus.

UR - http://www.scopus.com/inward/record.url?scp=17944376262&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=17944376262&partnerID=8YFLogxK

U2 - 10.1101/gr.GR1743R

DO - 10.1101/gr.GR1743R

M3 - Article

C2 - 11381030

AN - SCOPUS:17944376262

VL - 11

SP - 1034

EP - 1042

JO - PCR Methods and Applications

JF - PCR Methods and Applications

SN - 1088-9051

IS - 6

ER -