title: Genomic differences between estrogen receptor (ER)-positive and ER-negative human breast carcinoma identified by single nucleotide polymorphism array comparative genome hybridization analysis.
abstract: BACKGROUND
  Estrogen receptor (ER) remains one of the most important biomarkers for breast cancer subtyping and prognosis, and comparative genome hybridization has greatly contributed to the understanding of global genetic imbalance. The authors used single-nucleotide polymorphism (SNP) arrays to compare overall copy number aberrations (CNAs) as well as loss of heterozygosity (LOH) of the entire human genome in ER-positive and ER-negative breast carcinomas.
  
  
  METHODS
  DNA was extracted from frozen tumor sections of 21 breast carcinoma specimens and analyzed with a proprietary 50K XbaI SNP array. Copy number and LOH probability values were derived for each sample. Data were analyzed using bioinformatics and computational software, and permutation tests were used to estimate the significance of these values.
  
  
  RESULTS
  There was a global increase in CNAs and LOH in ER-negative relative to ER-positive cancers. Gain of the long arm of chromosome 1 (1q) and 8q were the most obvious changes common in both subtypes: An increase in the chromosome 1 short arm (1p)/1q ratio was observed in ER-negative samples, and an increased 16p/16q ratio was observed in ER-positive samples. Significant CNAs (adjusted P<.05) in ER-negative relative to ER-positive tumors included 5q deletion, loss of 15q, and gain of 2p and 21q. Copy-neutral LOH (cnLOH) common to both ER-positive and ER-negative samples included 9p21, the p16 tumor suppressor locus, and 4q13, the RCHY1 (ring finger and CHY zinc finger domain-containing 1) oncogene locus. Of particular interest was an enrichment of 17q LOH among the ER-negative tumors, potentially suggesting breast cancer 1 gene (BRCA1) mutations.
  
  
  CONCLUSIONS
  SNP array detected both genetic imbalances and cnLOH and was capable of discriminating ER-negative breast cancer from ER-positive breast cancer.
authors.affiliation: Fired Hutchinson Cancer Research Center, Seattle, WA 98109-1023, USA. mfang@fhcrc.org
authors.forename: Min
authors.initials: M
authors.lastname: Fang
authors.forename: Jessica
authors.initials: J
authors.lastname: Toher
authors.forename: Martin
authors.initials: M
authors.lastname: Morgan
authors.forename: Jerry
authors.initials: J
authors.lastname: Davison
authors.forename: Susan
authors.initials: S
authors.lastname: Tannenbaum
authors.forename: Kevin
authors.initials: K
authors.lastname: Claffey
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics*; D056915:DNA Copy Number Variations; D005260:Female; D014644:Genetic Variation; D042822:Genomic Instability; D006801:Humans; D019656:Loss of Heterozygosity; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D011960:Receptors, Estrogen / Q000378:metabolism*
chemical_list: D011960:Receptors, Estrogen