Are ER+PR+ and ER+PR鈭?breast tumors genetically different? A CGH array study

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• 作者：Alma Carracedo^a ; ^b ; Marta Salido^a ; Josep M. Corominas^c ; Federico Rojo^c ; Bibiana I. Ferreira^d ; Javier Suela^d ; Ignasi Tusquets^e ; Cristina Corzo^f ; Marcel Segura^g ; Blanca Espinet^a ; Juan C. Cigudosa^d ; Montserrat Arumi^c ; Joan Albanell^c ; ^e ; Sergi Serrano^c ; Francesc Solé ; ^a ; ^b ; ^{FSole@parcdesalutmar.cat}
• 关键词：breast ; PR ; ER ; cancer ; CGH array
• 刊名：Cancer Genetics
• 出版年：2012
• 期刊代码：pca82_22107762
• 类别：med
• 出版时间：April, 2012
• 卷：205
• 期：4
• 页码：138-146
• 文件大小：606 K

摘要

The estrogen receptor (ER) is a well-known predictor of breast cancer response to endocrine therapy. ER+ progesterone receptor (PR)鈭?breast tumors have a poorer response to endocrine therapy and a more aggressive phenotype than ER+PR+ tumors. A comparative genomic hybridization array technique was used to examine 25 ER+PR+ and 23 ER+PR鈭?tumors. Tissue microarrays composed of 50 ER+PR+ and 50 ER+PR鈭?tumors were developed to validate the comparative genomic hybridization array results. The genes of interest were analyzed by fluorescence in situ hybridization. The ER+PR鈭?group had a slightly different genomic profile when compared with ER+PR+ tumors. Chromosomes 17 and 20 contained the most overlapping gains, and chromosomes 3, 8, 9, 14, 17, 21, and 22 contained the most overlapping losses when compared with the ER+PR+ group. The gained regions, 17q23.2-q23.3 and 20q13.12, and the lost regions, 3p21.32-p12.3, 9pter-p13.2, 17pter-p12, and 21pter-q21.1, occurred at different alteration frequencies and were statistically significant in the ER+PR鈭?tumors compared with the ER+PR+ tumors. ER+PR鈭?breast tumors have a different genomic profile compared with ER+PR+ tumors. Differentially lost regions in the ER+PR鈭?group included genes with tumor suppressor functions and genes involved in apoptosis, mitosis, angiogenesis, and cell spreading. Differentially gained regions included genes such as MAP3K3, RPS6KB1, and ZNF217. Amplification of these genes could contribute to resistance to apoptosis, increased activation of the PI3K/Akt/mTOR pathway, and the loss of PR in at least some ER+PR鈭?tumors.