title: Loss of heterozygosity at D14S62 and metastatic potential of breast cancer.
abstract: BACKGROUND
  In breast cancer progression, the prevalence of damage at specific genetic loci often increases with the stage of the lesion (i.e., from noninvasive to invasive to metastatic). By use of genetic markers and analysis of allelic imbalances (loss of heterozygosity [LOH]) to compare DNA samples from paired normal and breast tumor tissues, we examined whether specific genetic changes in primary breast cancers can serve as biomarkers of metastatic potential.
  
  
  METHODS
  DNA samples from 76 patients with primary breast cancer (42 with axillary lymph node-negative disease and 34 with axillary lymph node-positive disease) were genotyped with four genetic markers spanning chromosome 14q31-q32. The intensity ratios of the two genetic alleles in normal-tumor DNA pairs were examined in genetically informative individuals. LOH was scored when the tumor allele intensity ratio (tumor allele 1/tumor allele 2) divided by the normal allele intensity ratio (normal allele 1/normal allele 2) was either less than 0.71 (tumor allele 1 LOH) or greater than 1. 4 (tumor allele 2 LOH).
  
  
  CONCLUSIONS
  Contrary to our expectations, we found statistically significantly more LOH events at markers D14S62 (two-sided P =.001) and D14S51 (two-sided P =.02) in primary breast cancers from patients with lymph node-negative disease versus lymph node-positive disease, suggesting the presence of a gene in this region that affects metastatic potential. Analysis of small interstitial or terminal deletions in the tumors of six especially informative patients with lymph node-negative disease places the putative metastasis-related gene in a 1490-kilobase region near D14S62.
  
  
  CONCLUSIONS
  LOH in the D14S62 region may impede the process of metastasis. Therefore, the D14S62 region LOH profile may have prognostic implications, and the isolation of the metastasis-related gene(s) in this region may lead to better diagnosis and treatment of breast cancer.
authors.affiliation: Department of Pathology, The University of Texas Health Science Center at San Antonio, USA.
authors.forename: P
authors.initials: P
authors.lastname: O'Connell
authors.forename: K
authors.initials: K
authors.lastname: Fischbach
authors.forename: S
authors.initials: S
authors.lastname: Hilsenbeck
authors.forename: S K
authors.initials: SK
authors.lastname: Mohsin
authors.forename: S A
authors.initials: SA
authors.lastname: Fuqua
authors.forename: G M
authors.initials: GM
authors.lastname: Clark
authors.forename: C K
authors.initials: CK
authors.lastname: Osborne
authors.forename: D C
authors.initials: DC
authors.lastname: Allred
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity; D008207:Lymphatic Metastasis; D008940:Mitotic Index
chemical_list: D014408:Biomarkers, Tumor; D017931:DNA Primers; D004273:DNA, Neoplasm