P2-06-01: Genomic Instability in Breast Cancers from Atomic Bomb Survivors: An Analysis of Microarray-Comparative Genomic Hybridization with Old Archival Tissues.

Abstract

Abstract Background: Sixty-six years after two atomic bombs (A-bombs) explosion on Hiroshima and Nagasaki, the incidence of breast cancer in A-bomb survivors still higher than that in controlled populations. We have reported a higher incidence of HER2 and C-MYC oncogene amplification in breast cancers from A-bomb survivors, which suggested genomic instability (GIN) induced by A-bomb radiation exposure might promote breast carcinogenesis in A-bomb survivors. The purpose of this study was to clarify the effect of A-bomb radiation exposure on GIN in breast cancer using microarray-comparative genomic hybridization (aCGH). Materials and Methods: DNA was extracted from the paraffin-embedded tissues of invasive ductal cancers from 11 survivors exposed at 1.5km from the hypocenter and 9 calendar year-matched non-exposed patients followed by aCGH analysis using a high-density oligonucleotide microarray (Agilent® SurePrint G3 8×60k microarray). The total length of chromosomal aberrant region was used as an indicator of GIN, and correlation with clinicopathological factors were statistically tested. Results: The mean of the derivative log ratio spread (DLRSpread), which estimates the log ratio noise by calculating the spread of log ratio differences between consecutive probes along all chromosomes, was 0.60 (range, 0.30 to 1.05). The concordance of aCGH results with FISH results for HER2 gene amplification was 90%. Samples from A-bomb survivors had significantly more copy number aberrations (CNA) than samples from control patients (P= 0.040). Samples with C-MYC gene amplification determined by aCGH analysis tended to harbor more CNA (P= 0.20), and age at the time of diagnosis tended to be inversely associated with the total length of chromosomal aberrant regions (P= 0.13). The multivariate analysis with covariance revealed that the status of A-bomb exposure was the only independent factor which was significantly associated the total length of chromosomal aberrant regions (P= 0.0324). Conclusions: This study suggested that A-bomb radiation may affect the development of chromosomal aberrant regions including oncogene amplification by inducing GIN and may be associated with a higher histological grade in breast cancer found in A-bomb survivors. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-06-01.