This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rennstam, K. Articles by Isola, J. Search for Related Content PubMed PubMed Citation Articles by Rennstam, K. Articles by Isola, J.

Patterns of Chromosomal Imbalances Defines Subgroups of Breast Cancer with Distinct Clinical Features and Prognosis. A Study of 305 Tumors by Comparative Genomic Hybridization

¹ Jubileum Institute, Department of Oncology, University Hospital, Lund, Sweden, and
² Institute of Medical Technology, Tampere University and University Hospital, Tampere, Finland

Chromosomal copy number aberrations (CNAs) are common in breast cancer and involve genomic regions in a frequency and combination, suggesting distinct routes of tumor development. We studied chromosomal gains (+) and losses (-) by comparative genomic hybridization from a series of 305 unselected primary invasive breast cancers. CNAs were observed in >90% of the tumors and involved all chromosomal arms in various frequencies, the most common being +1q (55%), +8q (41%), +16p (40%), +17q (28%), -13q (27%), -16q (22%), +20q (19%), -8p (18%), and +11q (16%). Eighteen pairs of CNAs were revealed as significantly associated using Fisher’s exact test with Bonferroni correction, the most common pairs being -8p/+8q, +17q/+20q, and -4q/-13q. To study more complex relationships between individual CNAs, principal component analysis and distance-based tree modeling were performed independently. Three distinct patterns of CNAs were observed. Group A was defined by +1q, +16p, and -16q, group B by +11q, +20q, +17q, and -13q, and group C by -8p and +8q. Group A was correlated to positive estrogen receptor and progesterone receptor (PgR) status (P < 0.001 and P < 0.05, respectively). Groups B and C were correlated to DNA nondiploidy (P < 0.001 and P < 0.05), high histological grade and lymph node positivity (P < 0.05), and group B also to high proliferation rate, large primary tumor size (P < 0.001), and negative PgR status (P < 0.05). Patients with aberrations in group A only had a significantly higher breast cancer survival rate than all other patients. The worst survival was seen for patients with aberrations in group C only along with the patients displaying aberrations from all CNA pattern groups (ABC). The 5-year survival rates vary from 96% in group A to 56% in group C. These correlations were independent of node status, tumor size, and PgR status in a multivariate analysis. We conclude that patterns of copy number gains and losses define breast tumors with distinct clinicopathological features and patient prognosis.

This article has been cited by other articles:

				M. Shehata, I. Bieche, R. Boutros, J. Weidenhofer, S. Fanayan, L. Spalding, N. Zeps, K. Byth, R. K. Bright, R. Lidereau, et al. Nonredundant Functions for Tumor Protein D52-Like Proteins Support Specific Targeting of TPD52 Clin. Cancer Res., August 15, 2008; 14(16): 5050 - 5060. [Abstract] [Full Text] [PDF]

				V. V. Iakovlev, N. C.R. Arneson, V. Wong, C. Wang, S. Leung, G. Iakovleva, K. Warren, M. Pintilie, and S. J. Done Genomic Differences Between Pure Ductal Carcinoma In Situ of the Breast and that Associated with Invasive Disease: a Calibrated aCGH Study Clin. Cancer Res., July 15, 2008; 14(14): 4446 - 4454. [Abstract] [Full Text] [PDF]

				A. Buness, R. Kuner, M. Ruschhaupt, A. Poustka, H. Sultmann, and A. Tresch Identification of aberrant chromosomal regions from gene expression microarray studies applied to human breast cancer Bioinformatics, September 1, 2007; 23(17): 2273 - 2280. [Abstract] [Full Text] [PDF]

				P. Briassouli, F. Chan, K. Savage, J. S. Reis-Filho, and S. Linardopoulos Aurora-A Regulation of Nuclear Factor-{kappa}B Signaling by Phosphorylation of I{kappa}B{alpha} Cancer Res., February 15, 2007; 67(4): 1689 - 1695. [Abstract] [Full Text] [PDF]

				A E Pinto, L Roque, R Rodrigues, S Andre, and J Soares Frequent 7q gains in flow cytometric multiploid/hypertetraploid breast carcinomas: a study of chromosome imbalances by comparative genomic hybridisation J. Clin. Pathol., April 1, 2006; 59(4): 367 - 372. [Abstract] [Full Text] [PDF]

				D. E. Stange, B. Radlwimmer, F. Schubert, F. Traub, A. Pich, G. Toedt, F. Mendrzyk, U. Lehmann, R. Eils, H. Kreipe, et al. High-Resolution Genomic Profiling Reveals Association of Chromosomal Aberrations on 1q and 16p with Histologic and Genetic Subgroups of Invasive Breast Cancer Clin. Cancer Res., January 15, 2006; 12(2): 345 - 352. [Abstract] [Full Text] [PDF]

				L. Melchor, S. Alvarez, E. Honrado, J. Palacios, A. Barroso, O. Diez, A. Osorio, and J. Benitez The Accumulation of Specific Amplifications Characterizes Two Different Genomic Pathways of Evolution of Familial Breast Tumors Clin. Cancer Res., December 15, 2005; 11(24): 8577 - 8584. [Abstract] [Full Text] [PDF]

				A. M. Burger, Y. Gao, Y. Amemiya, H. J. Kahn, R. Kitching, Y. Yang, P. Sun, S. A. Narod, W. M. Hanna, and A. K. Seth A Novel RING-Type Ubiquitin Ligase Breast Cancer-Associated Gene 2 Correlates with Outcome in Invasive Breast Cancer Cancer Res., November 15, 2005; 65(22): 10401 - 10412. [Abstract] [Full Text] [PDF]

				A. M. Sieuwerts, M. E. Meijer-van Gelder, M. Timmermans, A. M.A.C. Trapman, R. R. Garcia, M. Arnold, A. J.W. Goedheer, H. Portengen, J. G.M. Klijn, and J. A. Foekens How ADAM-9 and ADAM-11 Differentially From Estrogen Receptor Predict Response to Tamoxifen Treatment in Patients with Recurrent Breast Cancer: a Retrospective Study Clin. Cancer Res., October 15, 2005; 11(20): 7311 - 7321. [Abstract] [Full Text] [PDF]

				J Packeisen, K Nakachi, W Boecker, B Brandt, and H Buerger Cytogenetic differences in breast cancer samples between German and Japanese patients J. Clin. Pathol., October 1, 2005; 58(10): 1101 - 1103. [Abstract] [Full Text] [PDF]

				M Lacroix, R-A Toillon, and G Leclercq Stable 'portrait' of breast tumors during progression: data from biology, pathology and genetics Endocr. Relat. Cancer, September 1, 2004; 11(3): 497 - 522. [Abstract] [Full Text] [PDF]