title: Genomic analysis of the 8p11-12 amplicon in familial breast cancer.
abstract: 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.
authors.affiliation: Human Genetics Group, Human Cancer Genetics Program, Spanish National Cancer Center (CNIO), Madrid, Spain.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Melchor
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Garcia
authors.forename: Emiliano
authors.initials: E
authors.lastname: Honrado
authors.forename: Jessica C M
authors.initials: JC
authors.lastname: Pole
authors.forename: Sara
authors.initials: S
authors.lastname: Alvarez
authors.forename: Paul A W
authors.initials: PA
authors.lastname: Edwards
authors.forename: Carlos
authors.initials: C
authors.lastname: Caldas
authors.forename: James D
authors.initials: JD
authors.lastname: Brenton
authors.forename: Javier
authors.initials: J
authors.lastname: Benítez
mesh_terms: D000328:Adult; D019313:BRCA1 Protein / Q000235:genetics; D024682:BRCA2 Protein / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D019927:Cyclin E / Q000032:analysis; D005192:Family Health; D005260:Female; D005784:Gene Amplification / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D015894:Genome, Human; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D008875:Middle Aged; D009693:Nucleic Acid Hybridization / Q000379:methods*; D011379:Prognosis
chemical_list: D019313:BRCA1 Protein; D024682:BRCA2 Protein; D019927:Cyclin E; D019394:Ki-67 Antigen