DNA Copy Number Aberrations in Breast Cancer by Array Comparative Genomic Hybridization

Array comparative genomic hybridization (CGH) has been popularly used for analyzing DNA copy number variations in diseases like cancer. In this study, we investigated 82 sporadic samples from 49 breast cancer patients using 1-Mb resolution bacterial artificial chromosome CGH arrays. A number of highly frequent genomic aberrations were discovered, which may act as “drivers” of tumor progression. Meanwhile, the genomic profiles of four “normal” breast tissue samples taken at least 2 cm away from the primary tumor sites were also found to have some genomic aberrations that recurred with high frequency in the primary tumors, which may have important implications for clinical therapy. Additionally, we performed class comparison and class prediction for various clinicopathological parameters, and a list of characteristic genomic aberrations associated with different clinicopathological phenotypes was compiled. Our study provides clues for further investigations of the underlying mechanisms of breast carcinogenesis.

[1]  Jian Li,et al.  Omics-based Profiling of Carcinoma of the Breast and Matched Regional Lymph Node Metastasis , 2022 .

[2]  S. Lakhani,et al.  Molecular evolution of breast cancer , 2005, The Journal of pathology.

[3]  Jane Fridlyand,et al.  Differentiation of lobular versus ductal breast carcinomas by expression microarray analysis. , 2003, Cancer research.

[4]  K. Chew,et al.  Tumor labeling indices of primary breast cancers and their regional lymph node metastases , 1993, Cancer.

[5]  C. Giardina,et al.  Prognostic factors in breast cancer: the predictive value of the Nottingham Prognostic Index in patients with a long-term follow-up that were treated in a single institution. , 2001, European journal of cancer.

[6]  D M Parkin,et al.  Statistics on cancer in China: cancer registration in 2002 , 2005, European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation.

[7]  C. D. HAAGENSEN,et al.  Diseases of the Breast , 1972 .

[8]  Roland Eils,et al.  High-Resolution Genomic Profiling Reveals Association of Chromosomal Aberrations on 1q and 16p with Histologic and Genetic Subgroups of Invasive Breast Cancer , 2006, Clinical Cancer Research.

[9]  Laura Biganzoli,et al.  Prognostic and predictive factors. , 2009, Cancer treatment and research.

[10]  Tom Walsh,et al.  Molecular pathology of breast cancer and its application to clinical management , 1997, Cancer and Metastasis Reviews.

[11]  J. Daling,et al.  Risk of mortality by histologic type of breast cancer among women aged 50 to 79 years. , 2003, Archives of internal medicine.

[12]  Stefan Handt,et al.  Differences in genetic alterations between primary lobular and ductal breast cancers detected by comparative genomic hybridization , 2001, The Journal of pathology.

[13]  M. Pike,et al.  Reproductive factors and breast cancer risk according to joint estrogen and progesterone receptor status: a meta-analysis of epidemiological studies , 2006, Breast Cancer Research.

[14]  T. Powles,et al.  Prognostic relavance of cerbB2 expression following neoadjuvant chemotherapy in patients in a randomised trial of neoadjuvant versus adjuvant chemoendocrine therapy , 2004, Breast Cancer Research and Treatment.

[15]  S Miyano,et al.  Open source clustering software. , 2004, Bioinformatics.

[16]  D. Pinkel,et al.  Array comparative genomic hybridization and its applications in cancer , 2005, Nature Genetics.

[17]  Lars Bolund,et al.  Integrating Proteomic and Functional Genomic Technologies in Discovery-driven Translational Breast Cancer Research* , 2003, Molecular & Cellular Proteomics.

[18]  D. M. Dent.  Axillary lymphadenectomy for breast cancer , 1996 .

[19]  D. Dent,et al.  Axillary lymphadenectomy for breast cancer. Paradigm shifts and pragmatic surgeons. , 1996, Archives of surgery.

[20]  Yudong D. He,et al.  Gene expression profiling predicts clinical outcome of breast cancer , 2002, Nature.

[21]  Christian A. Rees,et al.  Molecular portraits of human breast tumours , 2000, Nature.

[22]  Mikael Lundin,et al.  Amplification of erbB2 and erbB2 expression are superior to estrogen receptor status as risk factors for distant recurrence in pT1N0M0 breast cancer: a nationwide population-based study. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[23]  Huanming Yang,et al.  High-resolution mapping of genotype-phenotype relationships in cri du chat syndrome using array comparative genomic hybridization. , 2005, American journal of human genetics.

[24]  M. Wigler,et al.  Circular binary segmentation for the analysis of array-based DNA copy number data. , 2004, Biostatistics.

[25]  Satoru Miyano,et al.  Open source clustering software , 2004 .

[26]  H. Dai,et al.  No common denominator for breast cancer lymph node metastasis , 2005, British Journal of Cancer.

[27]  T. Rebbeck,et al.  Differential expression of E-cadherin in lobular and ductal neoplasms of the breast and its biologic and diagnostic implications. , 2001, American journal of clinical pathology.

[28]  Dieter Niederacher,et al.  Multistep carcinogenesis of breast cancer and tumour heterogeneity , 1997, Journal of Molecular Medicine.

[29]  Wei Zhang,et al.  Distinguishing key biological pathways between primary breast cancers and their lymph node metastases by gene function-based clustering analysis. , 2004, International journal of oncology.

[30]  Daniel F Hayes,et al.  Prognostic and predictive factors revisited. , 2005, Breast.

[31]  Karsten Schlüns,et al.  Patterns of chromosomal imbalances in invasive breast cancer , 2000, International journal of cancer.

[32]  J. Mesirov,et al.  Molecular classification of cancer: class discovery and class prediction by gene expression monitoring. , 1999, Science.

[33]  N. Natarajan,et al.  Breast cancer in the medial half. Results of 1978 national survey of the American College of surgeons , 1983, Cancer.

[34]  P. V. van Diest,et al.  Genetic analysis of 53 lymph node‐negative breast carcinomas by CGH and relation to clinical, pathological, morphometric, and DNA cytometric prognostic factors , 1998, The Journal of pathology.

[35]  Van,et al.  A gene-expression signature as a predictor of survival in breast cancer. , 2002, The New England journal of medicine.

[36]  David Botstein,et al.  Different gene expression patterns in invasive lobular and ductal carcinomas of the breast. , 2004, Molecular biology of the cell.

[37]  P J Drew,et al.  Genetic changes in breast cancer detected by comparative genomic hybridisation , 2000, International journal of cancer.

[38]  J Isola,et al.  Genetic alterations in lobular breast cancer by comparative genomic hybridization , 1997, International journal of cancer.

[39]  P. Cornillet‐Lefèbvre,et al.  Compilation of published comparative genomic hybridization studies. , 2002, Cancer genetics and cytogenetics.

[40]  R. Eckhardt,et al.  DNA index and cell cycle analysis of primary breast cancer and synchronous axillary lymph node metastases , 2005, Breast Cancer Research and Treatment.

[41]  S Hellman,et al.  Natural history of node-negative breast cancer: a study of 826 patients with long-term follow-up. , 1995, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[42]  Joseph Geradts,et al.  Differential gene expression patterns in HER2/neu-positive and -negative breast cancer cell lines and tissues. , 2002, The American journal of pathology.

[43]  E. Wit.  Design and Analysis of DNA Microarray Investigations , 2004, Human Genomics.

[44]  D. Albertson.  Profiling Breast Cancer by Array CGH , 2003, Breast Cancer Research and Treatment.

[45]  F. Révillion,et al.  ERBB2 oncogene in human breast cancer and its clinical significance. , 1998, European journal of cancer.

[46]  Heng Li,et al.  Snap: an integrated SNP annotation platform , 2006, Nucleic Acids Res..

[47]  M G Daidone,et al.  Proliferative activity of primary breast cancer and of synchronous lymph node metastases evaluated by [3H]‐thymidine labelling index , 1990, Cell and tissue kinetics.

[48]  C Caldas,et al.  Using array-comparative genomic hybridization to define molecular portraits of primary breast cancers , 2007, Oncogene.

[49]  I. Ellis,et al.  Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. , 2002, Histopathology.

[50]  Matthias D Hofer,et al.  Genomic profiling of hormone-naïve lymph node metastases in patients with prostate cancer. , 2006, Neoplasia.

[51]  Barbara J. Trask,et al.  Array Comparative Genomic Hybridization Analysis of Genomic Alterations in Breast Cancer Subtypes , 2004, Cancer Research.

[52]  Jane Fridlyand,et al.  Bioinformatics Original Paper a Comparison Study: Applying Segmentation to Array Cgh Data for Downstream Analyses , 2022 .

[53]  P. Hall,et al.  Prognostic and predictive factors. , 2004, Methods in molecular medicine.