Integrated profiling of basal and luminal breast cancers.
Basal and luminal are two molecular subtypes of breast cancer with opposite histoclinical features. We report a combined, high-resolution analysis of genome copy number and gene expression in primary basal and luminal breast cancers. First, we identified and compared genomic alterations in 45 basal and 48 luminal tumors by using 244K oligonucleotide array comparative genomic hybridization (aCGH). We found various genome gains and losses and rare high-level gene amplifications that may provide therapeutic targets. We show that gain of 10p is a new alteration in basal breast cancer and that a subregion of the 8p12 amplification is specific of luminal tumors. Rare high-level amplifications contained BCL2L2, CCNE, EGFR, FGFR2, IGF1R, NOTCH2, and PIK3CA. Potential gene breaks involved ETV6 and FLT3. Second, we analyzed both aCGH and gene expression profiles for 42 basal and 32 luminal breast cancers. The results support the existence of specific oncogenic pathways in basal and luminal breast cancers, involving several potential oncogenes and tumor suppressor genes (TSG). In basal tumors, 73 candidate oncogenes were identified in chromosome regions 1q21-23, 10p14, and 12p13 and 28 candidate TSG in regions 4q32-34 and 5q11-23. In luminal breast cancers, 33 potential oncogenes were identified in 1q21-23, 8p12-q21, 11q13, and 16p12-13 and 61 candidate TSG in 16q12-13, 16q22-24, and 17p13. HORMAD1 (P = 6.5 x 10(-5)) and ZNF703 (P = 7 x 10(-4)) were the most significant basal and luminal potential oncogenes, respectively. Finally, among 10p candidate oncogenes associated with basal subtype, we validated CDC123/C10orf7 protein as a basal marker.
Adélaïde
José
J
Marseille Cancer Research Center, Department of Molecular Oncology, Institut Paoli-Calmettes and UMR599 Institut National de la Santé et de la Recherche Médicale, Marseille, France.
Finetti
Pascal
P
Bekhouche
Ismahane
I
Repellini
Laetitia
L
Geneix
Jeannine
J
Sircoulomb
Fabrice
F
Charafe-Jauffret
Emmanuelle
E
Cervera
Nathalie
N
Desplans
Jérôme
J
Parzy
Daniel
D
Schoenmakers
Eric
E
Viens
Patrice
P
Jacquemier
Jocelyne
J
Birnbaum
Daniel
D
Bertucci
François
F
Chaffanet
Max
M
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology / Q000601:surgery; D001943:Breast Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D002874:Chromosome Mapping; D002898:Chromosomes, Human, Pair 8; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D005784:Gene Amplification; D020869:Gene Expression Profiling; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification
D004273:DNA, Neoplasm; D012334:RNA, Neoplasm