Genomic analysis of the 8p11-12 amplicon in familial breast cancer
Lorenzo Melchor
Human Genetics Group, Human Cancer Genetics Program, Spanish National Cancer Center (CNIO), Madrid, Spain
Search for more papers by this authorMaria J. Garcia
Human Genetics Group, Human Cancer Genetics Program, Spanish National Cancer Center (CNIO), Madrid, Spain
Department of Oncology, Cancer Genomics Program, Hutchison/MRC Research Center, University of Cambridge, Cambridge CB2 2XZ, United Kingdom
Search for more papers by this authorEmiliano Honrado
Human Genetics Group, Human Cancer Genetics Program, Spanish National Cancer Center (CNIO), Madrid, Spain
Search for more papers by this authorJessica C.M. Pole
Department of Pathology, Cancer Genomics Program, Hutchison/MRC Research Center, University of Cambridge, Cambridge CB2 2XZ, United Kingdom
Search for more papers by this authorSara Alvarez
Molecular Cytogenetics Group, Human Cancer Genetics Program, Spanish National Cancer Center (CNIO), Madrid, Spain
Search for more papers by this authorPaul A.W. Edwards
Department of Pathology, Cancer Genomics Program, Hutchison/MRC Research Center, University of Cambridge, Cambridge CB2 2XZ, United Kingdom
Search for more papers by this authorCarlos Caldas
Department of Oncology, Cancer Genomics Program, Hutchison/MRC Research Center, University of Cambridge, Cambridge CB2 2XZ, United Kingdom
Search for more papers by this authorJames D. Brenton
Department of Oncology, Cancer Genomics Program, Hutchison/MRC Research Center, University of Cambridge, Cambridge CB2 2XZ, United Kingdom
JDB is a Cancer Research UK Senior Clinical Research Fellow, Cancer Research, UK.
Search for more papers by this authorCorresponding Author
Javier Benítez
Human Genetics Group, Human Cancer Genetics Program, Spanish National Cancer Center (CNIO), Madrid, Spain
Human Genetics Group, Human Cancer Genetics Program, Spanish National Cancer Center (CNIO), Madrid, SpainSearch for more papers by this authorLorenzo Melchor
Human Genetics Group, Human Cancer Genetics Program, Spanish National Cancer Center (CNIO), Madrid, Spain
Search for more papers by this authorMaria J. Garcia
Human Genetics Group, Human Cancer Genetics Program, Spanish National Cancer Center (CNIO), Madrid, Spain
Department of Oncology, Cancer Genomics Program, Hutchison/MRC Research Center, University of Cambridge, Cambridge CB2 2XZ, United Kingdom
Search for more papers by this authorEmiliano Honrado
Human Genetics Group, Human Cancer Genetics Program, Spanish National Cancer Center (CNIO), Madrid, Spain
Search for more papers by this authorJessica C.M. Pole
Department of Pathology, Cancer Genomics Program, Hutchison/MRC Research Center, University of Cambridge, Cambridge CB2 2XZ, United Kingdom
Search for more papers by this authorSara Alvarez
Molecular Cytogenetics Group, Human Cancer Genetics Program, Spanish National Cancer Center (CNIO), Madrid, Spain
Search for more papers by this authorPaul A.W. Edwards
Department of Pathology, Cancer Genomics Program, Hutchison/MRC Research Center, University of Cambridge, Cambridge CB2 2XZ, United Kingdom
Search for more papers by this authorCarlos Caldas
Department of Oncology, Cancer Genomics Program, Hutchison/MRC Research Center, University of Cambridge, Cambridge CB2 2XZ, United Kingdom
Search for more papers by this authorJames D. Brenton
Department of Oncology, Cancer Genomics Program, Hutchison/MRC Research Center, University of Cambridge, Cambridge CB2 2XZ, United Kingdom
JDB is a Cancer Research UK Senior Clinical Research Fellow, Cancer Research, UK.
Search for more papers by this authorCorresponding Author
Javier Benítez
Human Genetics Group, Human Cancer Genetics Program, Spanish National Cancer Center (CNIO), Madrid, Spain
Human Genetics Group, Human Cancer Genetics Program, Spanish National Cancer Center (CNIO), Madrid, SpainSearch for more papers by this authorAbstract
Amplification of 8p11-12 has been recurrently reported in sporadic breast cancer. These studies define a complex molecular structure with a set of minimal amplified regions, and different putative oncogenes that show a strong correlation between amplification and over-expression such as ZNF703/FLJ14299, SPFH2/C8orf2, BRF2 and RAB11FIP. However, none of these studies were carried out on familial breast malignancies. We have studied the incidence, molecular features and clinical value of this amplification in familial breast tumors associated with BRCA1, BRCA2 and non-BRCA1/2 gene mutations. We detected 9 out of 80 familial tumors with this amplicon by chromosomal comparative genomic hybridization. Next, we used a high-resolution comparative genomic hybridization array covering the 8p11-12 region to characterize this chromosomal region. This approach allowed us to define 2 cores of common amplification that largely overlap with those reported in sporadic tumors. Our findings confirm the molecular complexity of this chromosomal region and indicate that this genomic event is a common alteration in breast cancer, present not only in sporadic but also in familial tumors. Finally, we found correlation between the 8p11-12 amplification and proliferation (Ki-67) and cyclin E expression, which further proves in familial tumors the poor prognosis association previously reported in sporadic breast cancer. © 2006 Wiley-Liss, Inc.
Supporting Information
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