The accumulation of specific amplifications characterizes two different genomic pathways of evolution of familial breast tumors.
OBJECTIVE
High-level DNA amplifications are recurrently found in breast cancer, and some of them are associated with poor patient prognosis. To determine their frequency and co-occurrence in familial breast cancer, we have analyzed 80 tumors previously characterized for BRCA1 and BRCA2 germ-line mutations (26 BRCA1, 18 BRCA2, and 36 non-BRCA1/2) using high-resolution comparative genomic hybridization.


RESULTS
Twenty-one regions were identified as recurrently amplified, such as 8q21-23 (26.25%), 17q22-25 (13.75%), 13q21-31 (12.50%), and 8q24 (11.25%), many of which were altered in each familial breast cancer group. These amplifications defined an amplifier phenotype that is correlated with a higher genomic instability. Based on these amplifications, two different genomic pathways have been established in association with 8q21-23 and/or 17q22-25 and with 13q21-31 amplification. These pathways are associated with specific genomic regions of amplification, carry specific immunohistochemical characteristics coincident with high and low aggressiveness, and have a trend to be associated with BRCA1 and BRCA2/X, respectively.


CONCLUSIONS
In summary, our data suggest the existence of two different patterns of evolution, probably common to familial and sporadic breast tumors.
Melchor
Lorenzo
L
Human Genetics Group, Human Cancer Genetics Programme, Spanish National Cancer Center, Madrid, Spain.
Alvarez
Sara
S
Honrado
Emiliano
E
Palacios
José
J
Barroso
Alicia
A
Díez
Orland
O
Osorio
Ana
A
Benítez
Javier
J
D001943:Breast Neoplasms / Q000235:genetics*; D002877:Chromosomes, Human; D019143:Evolution, Molecular; D005260:Female; D005784:Gene Amplification; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D015894:Genome, Human; D018095:Germ-Line Mutation; D006801:Humans