Microarray-based comparative genomic hybridisation of breast cancer patients receiving neoadjuvant chemotherapy - PubMed (original) (raw)
. 2007 Jan 29;96(2):341-51.
doi: 10.1038/sj.bjc.6603483. Epub 2006 Nov 28.
J S Reis-Filho, S J Cleator, T Dexter, A Mackay, P Simpson, K Fenwick, M Iravani, J Salter, M Hills, C Jones, A Ashworth, I E Smith, T Powles, M Dowsett
Affiliations
- PMID: 17133270
- PMCID: PMC2359992
- DOI: 10.1038/sj.bjc.6603483
Microarray-based comparative genomic hybridisation of breast cancer patients receiving neoadjuvant chemotherapy
J-Y Pierga et al. Br J Cancer. 2007.
Abstract
We analysed the molecular genetic profiles of breast cancer samples before and after neoadjuvant chemotherapy with combination doxorubicin and cyclophosphamide (AC). DNA was obtained from microdissected frozen breast core biopsies from 44 patients before chemotherapy. Additional samples were obtained before the second course of chemotherapy (D21) and after the completion of the treatment (surgical specimens) in 17 and 21 patients, respectively. Microarray-based comparative genome hybridisation was performed using a platform containing approximately 5800 bacterial artificial chromosome clones (genome-wide resolution: 0.9 Mb). Analysis of the 44 pretreatment biopsies revealed that losses of 4p, 4q, 5q, 12q13.11-12q13.12, 17p11.2 and 17q11.2; and gains of 1p, 2p, 7q, 9p, 11q, 19p and 19q were significantly associated with oestrogen receptor negativity. 16q21-q22.1 losses were associated with lobular and 8q24 gains with ductal types. Losses of 5q33.3-q4 and 18p11.31 and gains of 6p25.1-p25.2 and Xp11.4 were associated with HER2 amplification. No correlations between DNA copy number changes and clinical response to AC were found. Microarray-based comparative genome hybridisation analysis of matched pretreatment and D21 biopsies failed to identify statistically significant differences, whereas a comparison between matched pretreatment and surgical samples revealed a statistically significant acquired copy number gain on 11p15.2-11p15.5. The modest chemotherapy-driven genomic changes, despite profound loss of cell numbers, suggest that there is little therapeutic selection of resistant non-modal cell lineages.
Figures
Figure 1
Frequency of copy number changes in 44 invasive breast carcinomas. (A) Overall frequency of DNA copy number alterations found in 44 invasive breast carcinomas as defined by aCGH. The proportion of tumours in which each clone is gained (green bars) or lost (red bars) is plotted (y axis) for each BAC clone according to genomic location (x axis). Vertical dotted lines represent chromosome centromeres. (B) – Pearson's correlation matrix of all thresholded aCGH data for 29 ER-positive, invasive breast carcinomas. Strong positive correlations are plotted as dark red, strong negative correlations as dark blue. Note the associations between chromosomes 1p/8p, 1p/12q, 4q/8p, 7p/22, 8q/12q and 11q/12q. Bacterial artificial chromosome clones are plotted in genome order. (C) Pearson's correlation matrix of all thresholded aCGH data for 15 ER-negative, invasive breast carcinomas. Strong direct plotted as dark red, strong negative correlations as dark blue. Note the associations between chromosomes 1p and 7q, 16p and 17q, and strong inverse correlations between 1q and 14q, 2q and 9q, 4q and 15q, 6q and 11q, 7p and 11q, 7p and 12q, 9p and 16p, and 13q and 15q. Bacterial artificial chromosome clones are plotted in genome order.
Figure 2
Categorical analysis of copy number gains and losses between non-responders (_N_=20) and responders (_N_=24). Fisher's exact tests are carried out on the segmented values for each clone, and those with a _P_-value of less than 0.01 are plotted (inverse log10, y axis) according to genomic location (x axis).
Figure 3
Hierarchical clustering analysis (Ward's method/Euclidean distance) of matched pre- and post-chemotherapy samples (17 patients) (A) and pre-chemotherapy, post-chemotherapy and surgical samples (12 patients) (B). (b – before chemotherapy; a – after chemotherapy (day 21); s – surgical biopsy).
Figure 4
Categorical analysis of copy number gains and losses between matched pre-chemotherapy and surgical tumour samples (21 patients). Fisher's exact tests are carried out on the segmented values for each clone, and those with a _P_-value of less than 0.01 are plotted (inverse log10, y axis) according to genomic location (x axis).
Similar articles
- Genomic and immunophenotypical characterization of pure micropapillary carcinomas of the breast.
Marchiò C, Iravani M, Natrajan R, Lambros MB, Savage K, Tamber N, Fenwick K, Mackay A, Senetta R, Di Palma S, Schmitt FC, Bussolati G, Ellis LO, Ashworth A, Sapino A, Reis-Filho JS. Marchiò C, et al. J Pathol. 2008 Aug;215(4):398-410. doi: 10.1002/path.2368. J Pathol. 2008. PMID: 18484683 - Array comparative genomic hybridization analysis of genomic alterations in breast cancer subtypes.
Loo LW, Grove DI, Williams EM, Neal CL, Cousens LA, Schubert EL, Holcomb IN, Massa HF, Glogovac J, Li CI, Malone KE, Daling JR, Delrow JJ, Trask BJ, Hsu L, Porter PL. Loo LW, et al. Cancer Res. 2004 Dec 1;64(23):8541-9. doi: 10.1158/0008-5472.CAN-04-1992. Cancer Res. 2004. PMID: 15574760 - Genomic alterations identified by array comparative genomic hybridization as prognostic markers in tamoxifen-treated estrogen receptor-positive breast cancer.
Han W, Han MR, Kang JJ, Bae JY, Lee JH, Bae YJ, Lee JE, Shin HJ, Hwang KT, Hwang SE, Kim SW, Noh DY. Han W, et al. BMC Cancer. 2006 Apr 12;6:92. doi: 10.1186/1471-2407-6-92. BMC Cancer. 2006. PMID: 16608533 Free PMC article. - Genomic alterations in renal tumours: what have we learned in the era of comparative genomic hybridisation?
Moch H. Moch H. Pathology. 2004 Feb;36(1):51-7. doi: 10.1080/0031302032000174932. Pathology. 2004. PMID: 14757557 Review.
Cited by
- ZNF714 Supports Pro-Oncogenic Features in Lung Cancer Cells.
Oleksiewicz U, Machnik M, Sobocińska J, Molenda S, Olechnowicz A, Florczak A, Smolibowski M, Kaczmarek M. Oleksiewicz U, et al. Int J Mol Sci. 2023 Oct 24;24(21):15530. doi: 10.3390/ijms242115530. Int J Mol Sci. 2023. PMID: 37958512 Free PMC article. - Diverse Roles of Annexin A6 in Triple-Negative Breast Cancer Diagnosis, Prognosis and EGFR-Targeted Therapies.
Korolkova OY, Widatalla SE, Williams SD, Whalen DS, Beasley HK, Ochieng J, Grewal T, Sakwe AM. Korolkova OY, et al. Cells. 2020 Aug 7;9(8):1855. doi: 10.3390/cells9081855. Cells. 2020. PMID: 32784650 Free PMC article. Review. - Integrative analysis of copy number and gene expression in breast cancer using formalin-fixed paraffin-embedded core biopsy tissue: a feasibility study.
Iddawela M, Rueda O, Eremin J, Eremin O, Cowley J, Earl HM, Caldas C. Iddawela M, et al. BMC Genomics. 2017 Jul 11;18(1):526. doi: 10.1186/s12864-017-3867-3. BMC Genomics. 2017. PMID: 28697743 Free PMC article. - bc-GenExMiner 3.0: new mining module computes breast cancer gene expression correlation analyses.
Jézéquel P, Frénel JS, Campion L, Guérin-Charbonnel C, Gouraud W, Ricolleau G, Campone M. Jézéquel P, et al. Database (Oxford). 2013 Jan 15;2013:bas060. doi: 10.1093/database/bas060. Print 2013. Database (Oxford). 2013. PMID: 23325629 Free PMC article. - 17p12 deletion in breast cancer predicts resistance to neoadjuvant chemotherapy.
Han W, Woo JH, Jeon YK, Yang SJ, Cho J, Ko E, Kim TY, Im SA, Oh DY, Park IA, Hwang KT, Moon HG, Yang KS, Noh DY. Han W, et al. Exp Ther Med. 2011 Sep;2(5):799-804. doi: 10.3892/etm.2011.299. Epub 2011 Jun 29. Exp Ther Med. 2011. PMID: 22977578 Free PMC article.
References
- Albertson DG (2003) Profiling breast cancer by array CGH. Breast Cancer Res Treat 78: 289–298 - PubMed
- Atienza JM, Roth RB, Rosette C, Smylie KJ, Kammerer S, Rehbock J, Ekblom J, Denissenko MF (2005) Suppression of RAD21 gene expression decreases cell growth and enhances cytotoxicity of etoposide and bleomycin in human breast cancer cells. Mol Cancer Ther 4: 361–368 - PubMed
- Ayers M, Symmans WF, Stec J, Damokosh AI, Clark E, Hess K, Lecocke M, Metivier J, Booser D, Ibrahim N, Valero V, Royce M, Arun B, Whitman G, Ross J, Sneige N, Hortobagyi GN, Pusztai L (2004) Gene expression profiles predict complete pathologic response to neoadjuvant paclitaxel and fluorouracil, doxorubicin, and cyclophosphamide chemotherapy in breast cancer. J Clin Oncol 22: 2284–2293 - PubMed
- Brenton JD, Carey LA, Ahmed AA, Caldas C (2005) Molecular classification and molecular forecasting of breast cancer: ready for clinical application? J Clin Oncol 23: 7350–7360 - PubMed
- Buerger H, Otterbach F, Simon R, Poremba C, Diallo R, Decker T, Riethdorf L, Brinkschmidt C, Dockhorn-Dworniczak B, Boecker W (1999a) Comparative genomic hybridization of ductal carcinoma in situ of the breast-evidence of multiple genetic pathways. J Pathol 187: 396–402 - PubMed
MeSH terms
LinkOut - more resources
Full Text Sources
Medical
Research Materials
Miscellaneous