DNA copy number aberrations associated with aneuploidy and chromosomal instability in breast cancers.
Biological characteristics of a tumor are primarily affected by its genomic alterations. It is thus important to ascertain whether there are genomic changes linked with DNA ploidy and/or chromosomal instability (CIN). In the present study, using fresh-frozen samples of 46 invasive breast cancers, laser scanning cytometry, array-based comparative genomic hybridization, and chromosome fluorescence in situ hybridization were performed to assess DNA ploidy, DNA copy number aberrations (DCNAs), and CIN status. Both ploidy and CIN status were examined in 36 tumors, resulting in 23 aneuploid/CIN+ tumors, 1 aneuploid/CIN-, 2 diploid/CIN+, and 10 diploid/CIN- tumors. Comparison of the aCGH data with the DNA ploidy and CIN status identified cytogenetically 11 characteristic breast cancers with distinctive DCNAs. The 11 tumors were classified into two types; one type is diploid/CIN- phenotype containing 4 DCNAs, and the other aneuploid/CIN+ phenotype containing 7 DCNAs. In 30 (65.2%) of the 36 breast cancers, the status of DNA ploidy and CIN depended on the type of DCNAs. Furthermore, the DNA ploidy phenotype depended on the dominant type of DCNAs even in tumors with a mixture of multiple DCNAs of one type and a single DCNA of the other type. Tumors with multiple DCNAs of both types represented aneuploidy and over three quarters of breast cancers carry at least one type of the DCNAs. These results suggested that, in breast cancers, the status of DNA ploidy and CIN was likely to determine at the beginning of carcinogenesis.
Kawauchi
Shigeto
S
Department of Pathology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan. shig@yamaguchi-u.ac.jp
Furuya
Tomoko
T
Ikemoto
Kenzo
K
Nakao
Motonao
M
Yamamoto
Shigeru
S
Oka
Masaaki
M
Sasaki
Kohsuke
K
D000328:Adult; D000368:Aged; D000782:Aneuploidy; D001943:Breast Neoplasms / Q000235:genetics*; D002469:Cell Separation; D043171:Chromosomal Instability; D055028:Comparative Genomic Hybridization; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D005434:Flow Cytometry; D018628:Gene Dosage; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D018613:Microscopy, Confocal; D008875:Middle Aged
D004273:DNA, Neoplasm