title: DNA copy number alterations and expression of relevant genes in triple-negative breast cancer.
abstract: Triple-negative breast cancer (TNBC) is defined by a lack of expression of estrogen, progesterone, and HER2 receptors, and genetically most of them fall into the basal subgroup of breast cancer. The important issue of TNBC is poorer clinical outcome and absence of effective targeted therapy. In this study, we sought to identify DNA copy number alterations and expression of relevant genes characteristic of TNBC to discover potential therapeutic targets. Frozen tissues from 114 breast cancers were analyzed using high-resolution array comparative genomic hybridization. The classification into subtype was determined by estrogen and progesterone receptor expression, and by the presence or absence of gain on the ERBB2 containing clone. The ACE algorithm was used for calling gain and loss of clones. Twenty-eight cases (25%) were classified as TNBC. Recurrent gains (> or =25%) unique to TNBC were 9p24-p21, 10p15-p13, 12p13, 13q31-q34, 18q12, 18q21-q23, and 21q22. Two published gene expression array data sets comparing basal subtype versus other subtype breast cancers were used for searching candidate genes. Of the genes upregulated in the basal subtype, 45 of 686 genes in one data set and 59 of 1,428 in the second data set were found to be located in the gained regions. Of these candidate genes, gain of NFIB (9p24.1) was specific for TNBC in a validation set by real-time PCR. In conclusion, we have identified recurrently gained regions characteristic of TNBC, and found that NFIB copy number and expression is increased in TNBC across the data sets. This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1045-2257/suppmat.
authors.affiliation: Department of Surgery, Seoul National University College of Medicine, Chongno-gu, Seoul 110-744, Korea.
authors.forename: Wonshik
authors.initials: W
authors.lastname: Han
authors.forename: Eun-Mi
authors.initials: EM
authors.lastname: Jung
authors.forename: Jihyoung
authors.initials: J
authors.lastname: Cho
authors.forename: Jong Won
authors.initials: JW
authors.lastname: Lee
authors.forename: Ki-Tae
authors.initials: KT
authors.lastname: Hwang
authors.forename: Song-Ju
authors.initials: SJ
authors.lastname: Yang
authors.forename: Jason Jongho
authors.initials: JJ
authors.lastname: Kang
authors.forename: Ji-Yeon
authors.initials: JY
authors.lastname: Bae
authors.forename: Yoon Kyung
authors.initials: YK
authors.lastname: Jeon
authors.forename: In-Ae
authors.initials: IA
authors.lastname: Park
authors.forename: Monica
authors.initials: M
authors.lastname: Nicolau
authors.forename: Stefanie S
authors.initials: SS
authors.lastname: Jeffrey
authors.forename: Dong-Young
authors.initials: DY
authors.lastname: Noh
mesh_terms: D000328:Adult; D000368:Aged; D000465:Algorithms; D001943:Breast Neoplasms / Q000145:classification / Q000235:genetics* / Q000401:mortality; D018270:Carcinoma, Ductal, Breast / Q000145:classification / Q000235:genetics* / Q000401:mortality; D003199:Computer Systems; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005784:Gene Amplification; D018628:Gene Dosage; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D018734:Genes, erbB-2; D006801:Humans; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D011960:Receptors, Estrogen / Q000235:genetics; D011980:Receptors, Progesterone / Q000235:genetics
chemical_list: D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone