Molecular cytogenetic analysis of a human breast metastasis model

Identification of phenotype-specific chromosomal rearrangements

Steven Goodison, Carrie Viars, Virginia Urquidi

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

We have previously characterized an experimental system in which the role of candidate metastasis-related genes can be screened and tested. Monoclonal cell lines M4A4 and NM2C5 originated from the MDA-MB-435 breast tumor cell line but have opposite metastatic capabilities in vivo. To investigate gross genetic changes present in this model, we performed a detailed molecular cytogenetic evaluation of the parental cell line, the M4A4 and NM2C5 cell lines, and related clones of metastatic phenotype. Using a combination of spectral karyotyping (SKY), G-banding, and fluorescence in situ hybridization (FISH), we were able to resolve the identity of all common marker chromosomes present in MDA-MB-435 cells, and to define several chromosomal changes, which were specific to each monoclonal cell line. Twenty identical structural and numerical chromosomal aberrations, including trisomies of chromosomes 2 and 5 as well as t(1;7), t(1;10), t(8;11), t(8;15), and t(20;21), were present in all cell lines. The majority of translocations were relatively simple non-reciprocal rearrangements, most frequently involving chromosomes 19, 1, 6, and 20. Chromosomal gains of 1, 7q, 8q, and 20q are common alterations in breast cancer. The metastatic M4A4 cell line contained numerous unique chromosomal aberrations, of which an abnormal banding region on chromosome 22, abr(22), was the best clone-specific identifier. Conversely, the t(12;15)(q22;q26.1) was found exclusively in the non-metastatic NM2C5 cell line. The integration of these karyotypic data with other cytogenetic and genomic databases will enhance our ability to identify genes that play critical roles in cancer development and progression.

Original languageEnglish (US)
Pages (from-to)37-48
Number of pages12
JournalCancer Genetics and Cytogenetics
Volume156
Issue number1
DOIs
StatePublished - Jan 1 2005
Externally publishedYes

Fingerprint

Cytogenetic Analysis
Breast
Neoplasm Metastasis
Phenotype
Cell Line
Cytogenetics
Chromosome Aberrations
Clone Cells
Spectral Karyotyping
Breast Neoplasms
Chromosomes, Human, Pair 19
Chromosomes, Human, Pair 22
Chromosomes, Human, Pair 5
Chromosomes, Human, Pair 2
Chromosomes, Human, Pair 1
Trisomy
Tumor Cell Line
Fluorescence In Situ Hybridization
Genetic Markers
Genes

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Molecular Biology

Cite this

Molecular cytogenetic analysis of a human breast metastasis model : Identification of phenotype-specific chromosomal rearrangements. / Goodison, Steven; Viars, Carrie; Urquidi, Virginia.

In: Cancer Genetics and Cytogenetics, Vol. 156, No. 1, 01.01.2005, p. 37-48.

Research output: Contribution to journalArticle

@article{07a5bdb49f154d919a1ae0a4474b8190,
title = "Molecular cytogenetic analysis of a human breast metastasis model: Identification of phenotype-specific chromosomal rearrangements",
abstract = "We have previously characterized an experimental system in which the role of candidate metastasis-related genes can be screened and tested. Monoclonal cell lines M4A4 and NM2C5 originated from the MDA-MB-435 breast tumor cell line but have opposite metastatic capabilities in vivo. To investigate gross genetic changes present in this model, we performed a detailed molecular cytogenetic evaluation of the parental cell line, the M4A4 and NM2C5 cell lines, and related clones of metastatic phenotype. Using a combination of spectral karyotyping (SKY), G-banding, and fluorescence in situ hybridization (FISH), we were able to resolve the identity of all common marker chromosomes present in MDA-MB-435 cells, and to define several chromosomal changes, which were specific to each monoclonal cell line. Twenty identical structural and numerical chromosomal aberrations, including trisomies of chromosomes 2 and 5 as well as t(1;7), t(1;10), t(8;11), t(8;15), and t(20;21), were present in all cell lines. The majority of translocations were relatively simple non-reciprocal rearrangements, most frequently involving chromosomes 19, 1, 6, and 20. Chromosomal gains of 1, 7q, 8q, and 20q are common alterations in breast cancer. The metastatic M4A4 cell line contained numerous unique chromosomal aberrations, of which an abnormal banding region on chromosome 22, abr(22), was the best clone-specific identifier. Conversely, the t(12;15)(q22;q26.1) was found exclusively in the non-metastatic NM2C5 cell line. The integration of these karyotypic data with other cytogenetic and genomic databases will enhance our ability to identify genes that play critical roles in cancer development and progression.",
author = "Steven Goodison and Carrie Viars and Virginia Urquidi",
year = "2005",
month = "1",
day = "1",
doi = "10.1016/j.cancergencyto.2004.04.005",
language = "English (US)",
volume = "156",
pages = "37--48",
journal = "Cancer Genetics and Cytogenetics",
issn = "0165-4608",
publisher = "Elsevier Inc.",
number = "1",

}

TY - JOUR

T1 - Molecular cytogenetic analysis of a human breast metastasis model

T2 - Identification of phenotype-specific chromosomal rearrangements

AU - Goodison, Steven

AU - Viars, Carrie

AU - Urquidi, Virginia

PY - 2005/1/1

Y1 - 2005/1/1

N2 - We have previously characterized an experimental system in which the role of candidate metastasis-related genes can be screened and tested. Monoclonal cell lines M4A4 and NM2C5 originated from the MDA-MB-435 breast tumor cell line but have opposite metastatic capabilities in vivo. To investigate gross genetic changes present in this model, we performed a detailed molecular cytogenetic evaluation of the parental cell line, the M4A4 and NM2C5 cell lines, and related clones of metastatic phenotype. Using a combination of spectral karyotyping (SKY), G-banding, and fluorescence in situ hybridization (FISH), we were able to resolve the identity of all common marker chromosomes present in MDA-MB-435 cells, and to define several chromosomal changes, which were specific to each monoclonal cell line. Twenty identical structural and numerical chromosomal aberrations, including trisomies of chromosomes 2 and 5 as well as t(1;7), t(1;10), t(8;11), t(8;15), and t(20;21), were present in all cell lines. The majority of translocations were relatively simple non-reciprocal rearrangements, most frequently involving chromosomes 19, 1, 6, and 20. Chromosomal gains of 1, 7q, 8q, and 20q are common alterations in breast cancer. The metastatic M4A4 cell line contained numerous unique chromosomal aberrations, of which an abnormal banding region on chromosome 22, abr(22), was the best clone-specific identifier. Conversely, the t(12;15)(q22;q26.1) was found exclusively in the non-metastatic NM2C5 cell line. The integration of these karyotypic data with other cytogenetic and genomic databases will enhance our ability to identify genes that play critical roles in cancer development and progression.

AB - We have previously characterized an experimental system in which the role of candidate metastasis-related genes can be screened and tested. Monoclonal cell lines M4A4 and NM2C5 originated from the MDA-MB-435 breast tumor cell line but have opposite metastatic capabilities in vivo. To investigate gross genetic changes present in this model, we performed a detailed molecular cytogenetic evaluation of the parental cell line, the M4A4 and NM2C5 cell lines, and related clones of metastatic phenotype. Using a combination of spectral karyotyping (SKY), G-banding, and fluorescence in situ hybridization (FISH), we were able to resolve the identity of all common marker chromosomes present in MDA-MB-435 cells, and to define several chromosomal changes, which were specific to each monoclonal cell line. Twenty identical structural and numerical chromosomal aberrations, including trisomies of chromosomes 2 and 5 as well as t(1;7), t(1;10), t(8;11), t(8;15), and t(20;21), were present in all cell lines. The majority of translocations were relatively simple non-reciprocal rearrangements, most frequently involving chromosomes 19, 1, 6, and 20. Chromosomal gains of 1, 7q, 8q, and 20q are common alterations in breast cancer. The metastatic M4A4 cell line contained numerous unique chromosomal aberrations, of which an abnormal banding region on chromosome 22, abr(22), was the best clone-specific identifier. Conversely, the t(12;15)(q22;q26.1) was found exclusively in the non-metastatic NM2C5 cell line. The integration of these karyotypic data with other cytogenetic and genomic databases will enhance our ability to identify genes that play critical roles in cancer development and progression.

UR - http://www.scopus.com/inward/record.url?scp=10044248882&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=10044248882&partnerID=8YFLogxK

U2 - 10.1016/j.cancergencyto.2004.04.005

DO - 10.1016/j.cancergencyto.2004.04.005

M3 - Article

VL - 156

SP - 37

EP - 48

JO - Cancer Genetics and Cytogenetics

JF - Cancer Genetics and Cytogenetics

SN - 0165-4608

IS - 1

ER -