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Cancer Genet. 2014 May;207(5):177-87. doi: 10.1016/j.cancergen.2014.04.007. Epub 2014 May 2.

Increased copy number of the DLX4 homeobox gene in breast axillary lymph node metastasis.

Author information

1
Department of Genetics, Federal University of Paraná, Curitiba, PR, Brazil.
2
Department of Biology, Federal University of Maranhão, São Luis, MA, Brazil.
3
Department of Biochemistry, University of Medicine and Pharmacy, Timisoara, Romania.
4
Innovation Center for Biomedical Informatics, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.
5
Breast Unit, Hospital Nossa Senhora das Graças, Curitiba, PR, Brazil.
6
Breast Unit, Hospital Nossa Senhora das Graças, Curitiba, PR, Brazil; Positivo University, Curitiba, PR, Brazil.
7
Department of Biochemistry and Molecular Medicine, George Washington University Medical Center, Washington, DC, USA.
8
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.
9
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA. Electronic address: lrc@georgetown.edu.

Abstract

DLX4 is a homeobox gene strongly implicated in breast tumor progression and invasion. Our main objective was to determine the DLX4 copy number status in sentinel lymph node (SLN) metastasis to assess its involvement in the initial stages of the axillary metastatic process. A total of 37 paired samples of SLN metastasis and primary breast tumors (PBT) were evaluated by fluorescence in situ hybridization, quantitative polymerase chain reaction and array comparative genomic hybridization assays. DLX4 increased copy number was observed in 21.6% of the PBT and 24.3% of the SLN metastasis; regression analysis demonstrated that the DLX4 alterations observed in the SLN metastasis were dependent on the ones in the PBT, indicating that they occur in the primary tumor cell populations and are maintained in the early axillary metastatic site. In addition, regression analysis demonstrated that DLX4 alterations (and other DLX and HOXB family members) occurred independently of the ones in the HER2/NEU gene, the main amplification driver on the 17q region. Additional studies evaluating DLX4 copy number in non-SLN axillary lymph nodes and/or distant breast cancer metastasis are necessary to determine if these alterations are carried on and maintained during more advanced stages of tumor progression and if could be used as a predictive marker for axillary involvement.

KEYWORDS:

DLX4; Homeobox gene; breast cancer; copy number; metastasis; sentinel lymph node

PMID:
24947980
PMCID:
PMC5806608
DOI:
10.1016/j.cancergen.2014.04.007
[Indexed for MEDLINE]
Free PMC Article

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