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. 2006 Oct 13:6:245.
doi: 10.1186/1471-2407-6-245.

Frequency, prognostic impact, and subtype association of 8p12, 8q24, 11q13, 12p13, 17q12, and 20q13 amplifications in breast cancers

Anne Letessier  1 , Fabrice Sircoulomb, Christophe Ginestier, Nathalie Cervera, Florence Monville, Véronique Gelsi-Boyer, Benjamin Esterni, Jeannine Geneix, Pascal Finetti, Christophe Zemmour, Patrice Viens, Emmanuelle Charafe-Jauffret, Jocelyne Jacquemier, Daniel Birnbaum, Max Chaffanet
Affiliations

Frequency, prognostic impact, and subtype association of 8p12, 8q24, 11q13, 12p13, 17q12, and 20q13 amplifications in breast cancers

Anne Letessier et al. BMC Cancer. .

Abstract

Background: Oncogene amplification and overexpression occur in tumor cells. Amplification status may provide diagnostic and prognostic information and may lead to new treatment strategies. Chromosomal regions 8p12, 8q24, 11q13, 17q12 and 20q13 are recurrently amplified in breast cancers.

Methods: To assess the frequencies and clinical impact of amplifications, we analyzed 547 invasive breast tumors organized in a tissue microarray (TMA) by fluorescence in situ hybridization (FISH) and calculated correlations with histoclinical features and prognosis. BAC probes were designed for: (i) two 8p12 subregions centered on RAB11FIP1 and FGFR1 loci, respectively; (ii) 11q13 region centered on CCND1; (iii) 12p13 region spanning NOL1; and (iv) three 20q13 subregions centered on MYBL2, ZNF217 and AURKA, respectively. Regions 8q24 and 17q12 were analyzed with MYC and ERBB2 commercial probes, respectively.

Results: We observed amplification of 8p12 (amplified at RAB11FIP1 and/or FGFR1) in 22.8%, 8q24 in 6.1%, 11q13 in 19.6%, 12p13 in 4.1%, 17q12 in 9.9%, 20q13Z (amplified at ZNF217 only) in 9.9%, and 20q13Co (co-amplification of two or three 20q13 loci) in 8.5% of cases. The 8q24, 12p13, and 17q12 amplifications were correlated with high grade. The most frequent single amplifications were 8p12 (9.8%), 8q24 (3.3%) and 12p13 (3.3%), 20q13Z and 20q13Co (1.6%) regions. The 17q12 and 11q13 regions were never found amplified alone. The most frequent co-amplification was 8p12/11q13. Amplifications of 8p12 and 17q12 were associated with poor outcome. Amplification of 12p13 was associated with basal molecular subtype.

Conclusion: Our results establish the frequencies, prognostic impacts and subtype associations of various amplifications and co-amplifications in breast cancers.

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Figures

Figure 1
Figure 1
Amplification regions and FISH probes. Schematic representation of the six regions analyzed with probes used in FISH experiments and the main corresponding genes. The number of informative cases and the percentage (frequency) of amplifications of each analyzed region is given in the table.
Figure 2
Figure 2
Co-amplification network. Schematic representation of frequencies of single amplifications and co-amplifications in 128 breast tumors samples. The size of spheres represents the frequency of region amplified as single. Lines of the same color represent co-amplification and the thickness of lines represents the frequency of the co-amplification: small: 1.6%, medium: 3.3%, large: 8.2%. For instance, the pink line linking 11q13, 8p12, 20q13Co and 20q13Z represents a co-amplification of all these regions found in 1.6% of informative cases (N = 128).
Figure 3
Figure 3
Amplification status and associated metastasis-free survival in breast cancer. A. Impact of the amplification of 8p12 region on MFS of the whole population (N = 219). B. Impact of the amplification of 8p12 region on MFS of N- patients (N = 114). C. Impact of the amplification of 17q12 region on MFS of the whole population (N = 272). D. Impact of the amplification of 17q12 region on MFS of N- patients (N = 140). E. Impact of the co-amplification of 8p12 and 17q12 regions on MFS of N- patients (N = 84). Kaplan-Meier curves illustrate MFS according to the status of amplification of different regions analyzed.
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