title: miRNA expression patterns in normal breast tissue and invasive breast cancers of BRCA1 and BRCA2 germ-line mutation carriers.
abstract: miRNA deregulation has been found to promote carcinogenesis. Little is known about miRNA deregulation in hereditary breast tumors as no miRNA expression profiling studies have been performed in normal breast tissue of BRCA1 and BRCA2 mutation carriers. miRNA profiles of 17 BRCA1- and 9 BRCA2-associated breast carcinomas were analyzed using microarrays. Normal breast tissues from BRCA1 and BRCA2 mutation carriers (both n = 5) and non-mutation carriers (n = 10) were also included. Candidate miRNAs were validated by qRT-PCR. Breast carcinomas showed extensive miRNA alteration compared to normal breast tissues in BRCA1 and BRCA2 mutation carriers. Moreover, normal breast tissue from BRCA1 mutation carriers already showed miRNA alterations compared to non-mutation carriers. Chromosomal distribution analysis showed several hotspots containing down- or up-regulated miRNAs. Pathway analysis yielded many similarities between the BRCA1 and BRCA2 axes with miRNAs involved in cell cycle regulation, proliferation and apoptosis. Lesser known pathways were also affected, including cellular movement and protein trafficking. This study provides a comprehensive insight into the potential role of miRNA deregulation in BRCA1/2-associated breast carcinogenesis. The observed extensive miRNA deregulation is likely the result of genome-wide effects of chromosomal instability caused by impaired BRCA1 or BRCA2 function. This study's results also suggest the existence of common pathways driving breast carcinogenesis in both BRCA1 and BRCA2 germ-line mutation carriers.
authors.affiliation: Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Shoko
authors.initials: S
authors.lastname: Vos
authors.affiliation: Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Farhad
authors.initials: F
authors.lastname: Vesuna
authors.affiliation: Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.|Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Venu
authors.initials: V
authors.lastname: Raman
authors.affiliation: Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.|Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: van Diest
authors.affiliation: Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Petra
authors.initials: P
authors.lastname: van der Groep
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018275:Carcinoma, Lobular / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018276:Carcinoma, Medullary / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D002877:Chromosomes, Human / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D007124:Immunoenzyme Techniques; D035683:MicroRNAs / Q000235:genetics*; D046228:Microarray Analysis; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D019313:BRCA1 Protein; D024682:BRCA2 Protein; D014408:Biomarkers, Tumor; D035683:MicroRNAs; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C492913:BRCA1 protein, human; C551750:BRCA2 protein, human; C508053:ERBB2 protein, human
keywords: BRCA1; BRCA2; breast cancer; hereditary; miRNA