PMID- 22152285
OWN - NLM
STAT- MEDLINE
DCOM- 20120615
LR  - 20211021
IS  - 1748-717X (Electronic)
IS  - 1748-717X (Linking)
VI  - 6
DP  - 2011 Dec 7
TI  - Significance of genomic instability in breast cancer in atomic bomb survivors: 
      analysis of microarray-comparative genomic hybridization.
PG  - 168
LID - 10.1186/1748-717X-6-168 [doi]
AB  - BACKGROUND: It has been postulated that ionizing radiation induces breast cancers 
      among atomic bomb (A-bomb) survivors. We have reported a higher incidence of HER2 
      and C-MYC oncogene amplification in breast cancers from A-bomb survivors. The 
      purpose of this study was to clarify the effect of A-bomb radiation exposure on 
      genomic instability (GIN), which is an important hallmark of carcinogenesis, in 
      archival formalin-fixed paraffin-embedded (FFPE) tissues of breast cancer by 
      using microarray-comparative genomic hybridization (aCGH). METHODS: Tumor DNA was 
      extracted from FFPE tissues of invasive ductal cancers from 15 survivors who were 
      exposed at 1.5 km or less from the hypocenter and 13 calendar year-matched 
      non-exposed patients followed by aCGH analysis using a high-density 
      oligonucleotide microarray. The total length of copy number aberrations (CNA) 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 noise by calculating the spread of log ratio 
      differences between consecutive probes for all chromosomes, was 0.54 (range, 0.26 
      to 1.05). The concordance of results between aCGH and fluorescence in situ 
      hybridization (FISH) for HER2 gene amplification was 88%. The incidence of HER2 
      amplification and histological grade was significantly higher in the A-bomb 
      survivors than control group (P = 0.04, respectively). The total length of CNA 
      tended to be larger in the A-bomb survivors (P = 0.15). Correlation analysis of 
      CNA and clinicopathological factors revealed that DLRSpread was negatively 
      correlated with that significantly (P = 0.034, r = -0.40). Multivariate analysis 
      with covariance revealed that the exposure to A-bomb was a significant (P = 
      0.005) independent factor which was associated with larger total length of CNA of 
      breast cancers. CONCLUSIONS: Thus, archival FFPE tissues from A-bomb survivors 
      are useful for genome-wide aCGH analysis. Our results suggested that A-bomb 
      radiation may affect the increased amount of CNA as a hallmark of GIN and, 
      subsequently, be associated with a higher histologic grade in breast cancer found 
      in A-bomb survivors.
FAU - Oikawa, Masahiro
AU  - Oikawa M
AD  - Department of Human Genetics, Atomic Bomb Disease Institute, Nagasaki University 
      Graduate School of Biomedical Sciences, Nagasaki, Japan.
FAU - Yoshiura, Koh-ichiro
AU  - Yoshiura K
FAU - Kondo, Hisayoshi
AU  - Kondo H
FAU - Miura, Shiro
AU  - Miura S
FAU - Nagayasu, Takeshi
AU  - Nagayasu T
FAU - Nakashima, Masahiro
AU  - Nakashima M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20111207
PL  - England
TA  - Radiat Oncol
JT  - Radiation oncology (London, England)
JID - 101265111
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Breast Neoplasms/*genetics/pathology
MH  - Carcinoma, Ductal, Breast/*genetics/pathology
MH  - Comparative Genomic Hybridization
MH  - Female
MH  - Gene Amplification
MH  - Genes, erbB-2/genetics/radiation effects
MH  - Genes, myc/genetics/radiation effects
MH  - Genomic Instability/*radiation effects
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Middle Aged
MH  - Neoplasm Grading
MH  - Neoplasms, Radiation-Induced/*genetics/pathology
MH  - *Nuclear Weapons
MH  - Oligonucleotide Array Sequence Analysis
MH  - *Survivors
PMC - PMC3280193
EDAT- 2011/12/14 06:00
MHDA- 2012/06/16 06:00
PMCR- 2011/12/07
CRDT- 2011/12/14 06:00
PHST- 2011/09/14 00:00 [received]
PHST- 2011/12/07 00:00 [accepted]
PHST- 2011/12/14 06:00 [entrez]
PHST- 2011/12/14 06:00 [pubmed]
PHST- 2012/06/16 06:00 [medline]
PHST- 2011/12/07 00:00 [pmc-release]
AID - 1748-717X-6-168 [pii]
AID - 10.1186/1748-717X-6-168 [doi]
PST - epublish
SO  - Radiat Oncol. 2011 Dec 7;6:168. doi: 10.1186/1748-717X-6-168.