DNA copy number alterations and expression of relevant genes in triple-negative breast cancer.
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.
Han
Wonshik
W
Department of Surgery, Seoul National University College of Medicine, Chongno-gu, Seoul 110-744, Korea.
Jung
Eun-Mi
EM
Cho
Jihyoung
J
Lee
Jong Won
JW
Hwang
Ki-Tae
KT
Yang
Song-Ju
SJ
Kang
Jason Jongho
JJ
Bae
Ji-Yeon
JY
Jeon
Yoon Kyung
YK
Park
In-Ae
IA
Nicolau
Monica
M
Jeffrey
Stefanie S
SS
Noh
Dong-Young
DY
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
D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone