Distinct genomic aberration patterns are found in familial breast cancer associated with different immunohistochemical subtypes.
Five breast cancer subtypes have been described in sporadic breast cancer (SBC) using expression arrays: basal-like, ERBB2, normal breast-like, luminal A and B. These molecular subtypes show different genomic aberration patterns (GAPs). Recently, our group described these breast cancer subtypes in 50 non-BRCA1/2 familial tumors using immunohistochemistry assays. We extended this study to the other classes of familial breast cancer (FBC), including 62 tumors (18 BRCA1, 16 BRCA2 and 28 non-BRCA1/2), with the same panel of 25 immunohistochemical (IHC) markers and histological grade obtaining a similar classification. We combined these data with results generated by a 1 Mb BAC array-based CGH study to evaluate the genomic aberrations of each group. We found that BRCA1-related tumors are preferentially basal-like, whereas non-BRCA1/2 familial tumors are mainly luminal A subtype. We described distinct GAPs related to each IHC subtype. Basal tumors had a greater number of gains/losses, while luminal B tumors had more high-level DNA amplifications. Our data are similar to those obtained in SBC studies, highlighting the existence of distinct genetic pathways of tumor evolution, common to both SBC and FBC.
Melchor
L
L
Human Genetics Group, Human Cancer Genetics Program, Spanish National Cancer Center (CNIO), Madrid, Spain.
Honrado
E
E
García
M J
MJ
Alvarez
S
S
Palacios
J
J
Osorio
A
A
Nathanson
K L
KL
Benítez
J
J
D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000145:classification* / Q000235:genetics* / Q000378:metabolism; D002869:Chromosome Aberrations; D002898:Chromosomes, Human, Pair 8; D016000:Cluster Analysis; D005190:Family; D005260:Female; D005784:Gene Amplification; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005787:Gene Frequency; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D018740:Genetic Heterogeneity; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis
D014408:Biomarkers, Tumor