title: Increased copy number of the DLX4 homeobox gene in breast axillary lymph node metastasis.
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.
authors.affiliation: Department of Genetics, Federal University of Paraná, Curitiba, PR, Brazil.
authors.forename: Clarissa
authors.initials: C
authors.lastname: Torresan
authors.affiliation: Department of Genetics, Federal University of Paraná, Curitiba, PR, Brazil.
authors.forename: Márcia M C
authors.initials: MM
authors.lastname: Oliveira
authors.affiliation: Department of Biology, Federal University of Maranhão, São Luis, MA, Brazil.
authors.forename: Silma R F
authors.initials: SR
authors.lastname: Pereira
authors.affiliation: Department of Genetics, Federal University of Paraná, Curitiba, PR, Brazil.
authors.forename: Enilze M S F
authors.initials: EM
authors.lastname: Ribeiro
authors.affiliation: Department of Biochemistry, University of Medicine and Pharmacy, Timisoara, Romania.
authors.forename: Catalin
authors.initials: C
authors.lastname: Marian
authors.affiliation: Innovation Center for Biomedical Informatics, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.
authors.forename: Yuriy
authors.initials: Y
authors.lastname: Gusev
authors.affiliation: Breast Unit, Hospital Nossa Senhora das Graças, Curitiba, PR, Brazil.
authors.forename: Rubens S
authors.initials: RS
authors.lastname: Lima
authors.affiliation: Breast Unit, Hospital Nossa Senhora das Graças, Curitiba, PR, Brazil; Positivo University, Curitiba, PR, Brazil.
authors.forename: Cicero A
authors.initials: CA
authors.lastname: Urban
authors.affiliation: Department of Biochemistry and Molecular Medicine, George Washington University Medical Center, Washington, DC, USA.
authors.forename: Patricia E
authors.initials: PE
authors.lastname: Berg
authors.affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.
authors.forename: Bassem R
authors.initials: BR
authors.lastname: Haddad
authors.affiliation: Department of Genetics, Federal University of Paraná, Curitiba, PR, Brazil.
authors.forename: Iglenir J
authors.initials: IJ
authors.lastname: Cavalli
authors.affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA. Electronic address: lrc@georgetown.edu.
authors.forename: Luciane R
authors.initials: LR
authors.lastname: Cavalli
mesh_terms: D000328:Adult; D000368:Aged; D001365:Axilla; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D005260:Female; D005801:Genes, Homeobox; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D021701:Sentinel Lymph Node Biopsy; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D018398:Homeodomain Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D014157:Transcription Factors; C105304:DLX4 protein, human; C508053:ERBB2 protein, human
keywords: DLX4; Homeobox gene; breast cancer; copy number; metastasis; sentinel lymph node