title: Microarray comparative genomic hybridization analysis of tubular breast carcinoma shows recurrent loss of the CDH13 locus on 16q.
abstract: Tubular breast carcinoma is a highly differentiated carcinoma with an excellent prognosis. Distinct genetic alterations in tubular breast carcinoma cells have been described, especially broad genetic losses on the q-arm of chromosome 16. These are more common in lobular breast carcinoma and low-grade ductal carcinoma in situ than in ductal breast carcinoma and high-grade ductal carcinoma in situ. To further delineate the molecular changes involved in tubular breast carcinoma more precisely, we examined 23 formalin-fixed and paraffin wax-embedded tissue samples (21 of tubular breast carcinoma and 2 of nonneoplastic breast epithelium) by microarray-based comparative genomic hybridization focusing on 287 genomic target clones of oncogenes and tumor suppressor genes. The results obtained from all nonneoplastic tissue samples of breast epithelium indicate no DNA copy number changes. In the tubular breast carcinoma samples, the highest frequencies for DNA sequence copy number losses were detected for CDH13 (in 86% of the samples) and MSH2, KCNK12 (in 52% of the samples). The highest frequencies of DNA sequence copy number gains were detected for HRAS and D13S319XYZ (each in 62% of the samples). Using principal component analysis, 3 subgroups of tubular breast carcinomas showing relative genetic changes were identified. For validation, the most frequent DNA copy number loss for CDH13 (18/21) was confirmed using fluorescence in situ hybridization in 4 of 5 tubular breast carcinomas analyzed. The newly identified genes with considerable copy number changes may include so far unknown candidate genes for the development and progression of tubular breast carcinoma, such as CDH13. The study provides the starting point for further delineating their detailed influence on the pathogenesis of tubular breast carcinoma.
authors.affiliation: Institute of Pathology, University Hospital Freiburg, Freiburg i. Br., Germany.
authors.forename: Marc-Oliver
authors.initials: MO
authors.lastname: Riener
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Nikolopoulos
authors.forename: Alexander
authors.initials: A
authors.lastname: Herr
authors.forename: Peter Johannes
authors.initials: PJ
authors.lastname: Wild
authors.forename: Michael
authors.initials: M
authors.lastname: Hausmann
authors.forename: Thorsten
authors.initials: T
authors.lastname: Wiech
authors.forename: Marzenna
authors.initials: M
authors.lastname: Orlowska-Volk
authors.forename: Silke
authors.initials: S
authors.lastname: Lassmann
authors.forename: Axel
authors.initials: A
authors.lastname: Walch
authors.forename: Martin
authors.initials: M
authors.lastname: Werner
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics*; D015820:Cadherins / Q000235:genetics*; D018270:Carcinoma, Ductal, Breast / Q000235:genetics*; D018275:Carcinoma, Lobular / Q000235:genetics; D002885:Chromosomes, Human, Pair 16; D055028:Comparative Genomic Hybridization; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D046228:Microarray Analysis; D008856:Microscopy, Fluorescence
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins; C099972:H-cadherin