Cargando…

BAC CGH-array identified specific small-scale genomic imbalances in diploid DMBA-induced rat mammary tumors

BACKGROUND: Development of breast cancer is a multistage process influenced by hormonal and environmental factors as well as by genetic background. The search for genes underlying this malignancy has recently been highly productive, but the etiology behind this complex disease is still not understoo...

Descripción completa

Detalles Bibliográficos
Autores principales: Samuelson, Emma, Karlsson, Sara, Partheen, Karolina, Nilsson, Staffan, Szpirer, Claude, Behboudi, Afrouz
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3488521/
https://www.ncbi.nlm.nih.gov/pubmed/22894538
http://dx.doi.org/10.1186/1471-2407-12-352
_version_ 1782248629083308032
author Samuelson, Emma
Karlsson, Sara
Partheen, Karolina
Nilsson, Staffan
Szpirer, Claude
Behboudi, Afrouz
author_facet Samuelson, Emma
Karlsson, Sara
Partheen, Karolina
Nilsson, Staffan
Szpirer, Claude
Behboudi, Afrouz
author_sort Samuelson, Emma
collection PubMed
description BACKGROUND: Development of breast cancer is a multistage process influenced by hormonal and environmental factors as well as by genetic background. The search for genes underlying this malignancy has recently been highly productive, but the etiology behind this complex disease is still not understood. In studies using animal cancer models, heterogeneity of the genetic background and environmental factors is reduced and thus analysis and identification of genetic aberrations in tumors may become easier. To identify chromosomal regions potentially involved in the initiation and progression of mammary cancer, in the present work we subjected a subset of experimental mammary tumors to cytogenetic and molecular genetic analysis. METHODS: Mammary tumors were induced with DMBA (7,12-dimethylbenz[a]anthrazene) in female rats from the susceptible SPRD-Cu3 strain and from crosses and backcrosses between this strain and the resistant WKY strain. We first produced a general overview of chromosomal aberrations in the tumors using conventional kartyotyping (G-banding) and Comparative Genome Hybridization (CGH) analyses. Particular chromosomal changes were then analyzed in more details using an in-house developed BAC (bacterial artificial chromosome) CGH-array platform. RESULTS: Tumors appeared to be diploid by conventional karyotyping, however several sub-microscopic chromosome gains or losses in the tumor material were identified by BAC CGH-array analysis. An oncogenetic tree analysis based on the BAC CGH-array data suggested gain of rat chromosome (RNO) band 12q11, loss of RNO5q32 or RNO6q21 as the earliest events in the development of these mammary tumors. CONCLUSIONS: Some of the identified changes appear to be more specific for DMBA-induced mammary tumors and some are similar to those previously reported in ACI rat model for estradiol-induced mammary tumors. The later group of changes is more interesting, since they may represent anomalies that involve genes with a critical role in mammary tumor development. Genetic changes identified in this work are at very small scales and thus may provide a more feasible basis for the identification of the target gene(s). Identification of the genes underlying these chromosome changes can provide new insights to the mechanisms of mammary carcinogenesis.
format Online
Article
Text
id pubmed-3488521
institution National Center for Biotechnology Information
language English
publishDate 2012
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-34885212012-11-05 BAC CGH-array identified specific small-scale genomic imbalances in diploid DMBA-induced rat mammary tumors Samuelson, Emma Karlsson, Sara Partheen, Karolina Nilsson, Staffan Szpirer, Claude Behboudi, Afrouz BMC Cancer Research Article BACKGROUND: Development of breast cancer is a multistage process influenced by hormonal and environmental factors as well as by genetic background. The search for genes underlying this malignancy has recently been highly productive, but the etiology behind this complex disease is still not understood. In studies using animal cancer models, heterogeneity of the genetic background and environmental factors is reduced and thus analysis and identification of genetic aberrations in tumors may become easier. To identify chromosomal regions potentially involved in the initiation and progression of mammary cancer, in the present work we subjected a subset of experimental mammary tumors to cytogenetic and molecular genetic analysis. METHODS: Mammary tumors were induced with DMBA (7,12-dimethylbenz[a]anthrazene) in female rats from the susceptible SPRD-Cu3 strain and from crosses and backcrosses between this strain and the resistant WKY strain. We first produced a general overview of chromosomal aberrations in the tumors using conventional kartyotyping (G-banding) and Comparative Genome Hybridization (CGH) analyses. Particular chromosomal changes were then analyzed in more details using an in-house developed BAC (bacterial artificial chromosome) CGH-array platform. RESULTS: Tumors appeared to be diploid by conventional karyotyping, however several sub-microscopic chromosome gains or losses in the tumor material were identified by BAC CGH-array analysis. An oncogenetic tree analysis based on the BAC CGH-array data suggested gain of rat chromosome (RNO) band 12q11, loss of RNO5q32 or RNO6q21 as the earliest events in the development of these mammary tumors. CONCLUSIONS: Some of the identified changes appear to be more specific for DMBA-induced mammary tumors and some are similar to those previously reported in ACI rat model for estradiol-induced mammary tumors. The later group of changes is more interesting, since they may represent anomalies that involve genes with a critical role in mammary tumor development. Genetic changes identified in this work are at very small scales and thus may provide a more feasible basis for the identification of the target gene(s). Identification of the genes underlying these chromosome changes can provide new insights to the mechanisms of mammary carcinogenesis. BioMed Central 2012-08-15 /pmc/articles/PMC3488521/ /pubmed/22894538 http://dx.doi.org/10.1186/1471-2407-12-352 Text en Copyright ©2012 Samuelson et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Samuelson, Emma
Karlsson, Sara
Partheen, Karolina
Nilsson, Staffan
Szpirer, Claude
Behboudi, Afrouz
BAC CGH-array identified specific small-scale genomic imbalances in diploid DMBA-induced rat mammary tumors
title BAC CGH-array identified specific small-scale genomic imbalances in diploid DMBA-induced rat mammary tumors
title_full BAC CGH-array identified specific small-scale genomic imbalances in diploid DMBA-induced rat mammary tumors
title_fullStr BAC CGH-array identified specific small-scale genomic imbalances in diploid DMBA-induced rat mammary tumors
title_full_unstemmed BAC CGH-array identified specific small-scale genomic imbalances in diploid DMBA-induced rat mammary tumors
title_short BAC CGH-array identified specific small-scale genomic imbalances in diploid DMBA-induced rat mammary tumors
title_sort bac cgh-array identified specific small-scale genomic imbalances in diploid dmba-induced rat mammary tumors
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3488521/
https://www.ncbi.nlm.nih.gov/pubmed/22894538
http://dx.doi.org/10.1186/1471-2407-12-352
work_keys_str_mv AT samuelsonemma baccgharrayidentifiedspecificsmallscalegenomicimbalancesindiploiddmbainducedratmammarytumors
AT karlssonsara baccgharrayidentifiedspecificsmallscalegenomicimbalancesindiploiddmbainducedratmammarytumors
AT partheenkarolina baccgharrayidentifiedspecificsmallscalegenomicimbalancesindiploiddmbainducedratmammarytumors
AT nilssonstaffan baccgharrayidentifiedspecificsmallscalegenomicimbalancesindiploiddmbainducedratmammarytumors
AT szpirerclaude baccgharrayidentifiedspecificsmallscalegenomicimbalancesindiploiddmbainducedratmammarytumors
AT behboudiafrouz baccgharrayidentifiedspecificsmallscalegenomicimbalancesindiploiddmbainducedratmammarytumors