Journal article
Microalterations of Inherently Unstable Genomic Regions in Rat Mammary Carcinomas as Revealed by Long Oligonucleotide Array-Based Comparative Genomic Hybridization
Cancer research (Chicago, Ill.), Vol.69(12), pp.5159-5167
06/15/2009
DOI: 10.1158/0008-5472.CAN-08-4038
PMID: 19509235
Abstract
The presence of copy number variants in normal genomes poses a challenge to identify small genuine somatic copy number changes in high-resolution cancer genome profiling studies due to the use of unpaired reference DNA. Another problem is the well-known rearrangements of immunoglobulin and T-cell receptor genes in lymphocytes (a commonly used reference), which may misdirect the researcher to a locus with no relevance in tumorigenesis. We here show real gains of the IgG heavy chain V gene region in carcinogen-induced rat mammary tumor samples after normalization to paired mammary gland, a tissue without lymphocyte infiltration. We further show that the segmental duplication region encompassing the IgG heavy chain V genes is a copy number variant between the susceptible (SS) and the resistant (BN) to mammary tumor development inbred rat strains. Our data suggest that the already inherently unstable genomic region is a convenient target for additional structural rearrangements (gains) at the somatic level when exposed to a carcinogen (7,12-dimethylbenz[a]anthracene), which subsequently seem to benefit tumor development in the mammary gland of the susceptible strain. Thus, the selection of an appropriate reference DNA enabled us to identify immunoglobulin genes as novel cancer targets playing a role in mammary tumor development. We conclude that control DNA in array-based comparative genomic hybridization experiments should be selected with care, and DNA from pooled spleen (contains immature lymphocytes and is used as reference in animal studies) or blood may not be the ideal control in the study of primary tumors. [Cancer Res 2009;69(12):5159-67]
Details
- Title: Subtitle
- Microalterations of Inherently Unstable Genomic Regions in Rat Mammary Carcinomas as Revealed by Long Oligonucleotide Array-Based Comparative Genomic Hybridization
- Creators
- Tatjana Adamovic - Medical College of WisconsinDonna McAllister - Medical College of WisconsinVictor Guryev - Leukemia and Lymphoma SocietyXujing Wang - University of Alabama SystemJaime Wendt Andrae - Medical College of WisconsinEdwin Cuppen - Hubrecht Institute for Developmental Biology and Stem Cell ResearchHoward J. Jacob - Medical College of WisconsinSonia L. Sugg - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Cancer research (Chicago, Ill.), Vol.69(12), pp.5159-5167
- DOI
- 10.1158/0008-5472.CAN-08-4038
- PMID
- 19509235
- NLM abbreviation
- Cancer Res
- ISSN
- 0008-5472
- eISSN
- 1538-7445
- Publisher
- Amer Assoc Cancer Research
- Number of pages
- 9
- Grant note
- Scott and Peggy Sampson Memorial Breast Cancer Research Fellowship Harley Riders Breast Cancer Research Fund Medical College of Wisconsin Breast Cancer Research Fund Healthier Wisconsin Research Initiative
- Language
- English
- Date published
- 06/15/2009
- Academic Unit
- Surgery
- Record Identifier
- 9984322945802771
Metrics
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