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Array comparative genomic hybridisation (aCGH) analysis of premenopausal breast cancers from a nuclear fallout area and matched cases from Western New York.

Varma G, Varma R, Huang H, Pryshchepava A, Groth J, Fleming D, Nowak NJ, McQuaid D, Conroy J, Mahoney M, Moysich K, Falkner KL, Geradts J - Br. J. Cancer (2005)

Bottom Line: HER2/neu negativity and younger age were also associated with a higher number of gains and fewer losses.In the five paired samples, we observed more discordant than concordant DNA changes.We identified a distinct CNA profile for carcinomas from a nuclear fallout area, suggesting a possible molecular fingerprint of radiation-associated breast cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA.

ABSTRACT
High-resolution array comparative genomic hybridisation (aCGH) analysis of DNA copy number aberrations (CNAs) was performed on breast carcinomas in premenopausal women from Western New York (WNY) and from Gomel, Belarus, an area exposed to fallout from the 1986 Chernobyl nuclear accident. Genomic DNA was isolated from 47 frozen tumour specimens from 42 patients and hybridised to arrays spotted with more than 3000 BAC clones. In all, 20 samples were from WNY and 27 were from Belarus. In total, 34 samples were primary tumours and 13 were lymph node metastases, including five matched pairs from Gomel. The average number of total CNAs per sample was 76 (range 35-134). We identified 152 CNAs (92 gains and 60 losses) occurring in more than 10% of the samples. The most common amplifications included gains at 8q13.2 (49%), at 1p21.1 (36%), and at 8q24.21 (36%). The most common deletions were at 1p36.22 (26%), at 17p13.2 (26%), and at 8p23.3 (23%). Belarussian tumours had more amplifications and fewer deletions than WNY breast cancers. HER2/neu negativity and younger age were also associated with a higher number of gains and fewer losses. In the five paired samples, we observed more discordant than concordant DNA changes. Unsupervised hierarchical cluster analysis revealed two distinct groups of tumours: one comprised predominantly of Belarussian carcinomas and the other largely consisting of WNY cases. In total, 50 CNAs occurred significantly more commonly in one cohort vs the other, and these included some candidate signature amplifications in the breast cancers in women exposed to significant radiation. In conclusion, our high-density aCGH study has revealed a large number of genetic aberrations in individual premenopausal breast cancer specimens, some of which had not been reported before. We identified a distinct CNA profile for carcinomas from a nuclear fallout area, suggesting a possible molecular fingerprint of radiation-associated breast cancer.

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Cluster analysis (dendrogram). Unsupervised hierarchical clustering based on 202 BAC clones (vertical) yielded two main arms (horizontal): 26 tumours predominantly from Belarus (blue) on the left and 21 tumours mainly from WNY (red) on the right.
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fig3: Cluster analysis (dendrogram). Unsupervised hierarchical clustering based on 202 BAC clones (vertical) yielded two main arms (horizontal): 26 tumours predominantly from Belarus (blue) on the left and 21 tumours mainly from WNY (red) on the right.

Mentions: Unsupervised hierarchical clustering using 202 discriminating BAC clones produced a dendrogram with two distinct arms: one predominantly composed of WNY carcinomas and the other mostly comprised of Belarussian samples (P<0.001) (Figure 3). These two arms were not significantly different with regard to patient age, primary tumours vs metastases, tumour size, nodal status, stage, grade, ER, or HER2 status. A total of 50 BAC clones were differentially amplified or deleted in premenopausal breast cancers from WNY and Belarus, and 25 of these contained named genes (Table 6). Of particular interest were 10 BAC clones that were amplified selectively in Belarussian tumours. Moreover, three of these BACs were specifically deleted in WNY cases. Two BAC clones with known genes were significantly more often amplified, and 13 were more frequently deleted in WNY tumours.


Array comparative genomic hybridisation (aCGH) analysis of premenopausal breast cancers from a nuclear fallout area and matched cases from Western New York.

Varma G, Varma R, Huang H, Pryshchepava A, Groth J, Fleming D, Nowak NJ, McQuaid D, Conroy J, Mahoney M, Moysich K, Falkner KL, Geradts J - Br. J. Cancer (2005)

Cluster analysis (dendrogram). Unsupervised hierarchical clustering based on 202 BAC clones (vertical) yielded two main arms (horizontal): 26 tumours predominantly from Belarus (blue) on the left and 21 tumours mainly from WNY (red) on the right.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2361621&req=5

fig3: Cluster analysis (dendrogram). Unsupervised hierarchical clustering based on 202 BAC clones (vertical) yielded two main arms (horizontal): 26 tumours predominantly from Belarus (blue) on the left and 21 tumours mainly from WNY (red) on the right.
Mentions: Unsupervised hierarchical clustering using 202 discriminating BAC clones produced a dendrogram with two distinct arms: one predominantly composed of WNY carcinomas and the other mostly comprised of Belarussian samples (P<0.001) (Figure 3). These two arms were not significantly different with regard to patient age, primary tumours vs metastases, tumour size, nodal status, stage, grade, ER, or HER2 status. A total of 50 BAC clones were differentially amplified or deleted in premenopausal breast cancers from WNY and Belarus, and 25 of these contained named genes (Table 6). Of particular interest were 10 BAC clones that were amplified selectively in Belarussian tumours. Moreover, three of these BACs were specifically deleted in WNY cases. Two BAC clones with known genes were significantly more often amplified, and 13 were more frequently deleted in WNY tumours.

Bottom Line: HER2/neu negativity and younger age were also associated with a higher number of gains and fewer losses.In the five paired samples, we observed more discordant than concordant DNA changes.We identified a distinct CNA profile for carcinomas from a nuclear fallout area, suggesting a possible molecular fingerprint of radiation-associated breast cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA.

ABSTRACT
High-resolution array comparative genomic hybridisation (aCGH) analysis of DNA copy number aberrations (CNAs) was performed on breast carcinomas in premenopausal women from Western New York (WNY) and from Gomel, Belarus, an area exposed to fallout from the 1986 Chernobyl nuclear accident. Genomic DNA was isolated from 47 frozen tumour specimens from 42 patients and hybridised to arrays spotted with more than 3000 BAC clones. In all, 20 samples were from WNY and 27 were from Belarus. In total, 34 samples were primary tumours and 13 were lymph node metastases, including five matched pairs from Gomel. The average number of total CNAs per sample was 76 (range 35-134). We identified 152 CNAs (92 gains and 60 losses) occurring in more than 10% of the samples. The most common amplifications included gains at 8q13.2 (49%), at 1p21.1 (36%), and at 8q24.21 (36%). The most common deletions were at 1p36.22 (26%), at 17p13.2 (26%), and at 8p23.3 (23%). Belarussian tumours had more amplifications and fewer deletions than WNY breast cancers. HER2/neu negativity and younger age were also associated with a higher number of gains and fewer losses. In the five paired samples, we observed more discordant than concordant DNA changes. Unsupervised hierarchical cluster analysis revealed two distinct groups of tumours: one comprised predominantly of Belarussian carcinomas and the other largely consisting of WNY cases. In total, 50 CNAs occurred significantly more commonly in one cohort vs the other, and these included some candidate signature amplifications in the breast cancers in women exposed to significant radiation. In conclusion, our high-density aCGH study has revealed a large number of genetic aberrations in individual premenopausal breast cancer specimens, some of which had not been reported before. We identified a distinct CNA profile for carcinomas from a nuclear fallout area, suggesting a possible molecular fingerprint of radiation-associated breast cancer.

Show MeSH
Related in: MedlinePlus