title: Identifying early events of gene expression in breast cancer with systems biology phylogenetics.
abstract: Advanced omics technologies such as deep sequencing and spectral karyotyping are revealing more of cancer heterogeneity at the genetic, genomic, gene expression, epigenetic, proteomic, and metabolomic levels. With this increasing body of emerging data, the task of data analysis becomes critical for mining and modeling to better understand the relevant underlying biological processes. However, the multiple levels of heterogeneity evident within and among populations, healthy and diseased, complicate the mining and interpretation of biological data, especially when dealing with hundreds to tens of thousands of variables. Heterogeneity occurs in many diseases, such as cancers, autism, macular degeneration, and others. In cancer, heterogeneity has hampered the search for validated biomarkers for early detection, and it has complicated the task of finding clonal (driver) and nonclonal (nonexpanded or passenger) aberrations. We show that subtyping of cancer (classification of specimens) should be an a priori step to the identification of early events of cancers. Studying early events in oncogenesis can be done on histologically normal tissues from diseased individuals (HNTDI), since they most likely have been exposed to the same mutagenic insults that caused the cancer in their neighboring tissues. Polarity assessment of HNTDI data variables by using healthy specimens as outgroup(s), followed by the application of parsimony phylogenetic analysis, produces a hierarchical classification of specimens that reveals the early events of the disease ontogeny within its subtypes as shared derived changes (abnormal changes) or synapomorphies in phylogenetic terminology.
authors.affiliation: Section of Immunopathology, National Eye Institute, National Institutes of Health, Bethesda, Md., USA.
authors.forename: M S
authors.initials: MS
authors.lastname: Abu-Asab
authors.forename: N
authors.initials: N
authors.lastname: Abu-Asab
authors.forename: C A
authors.initials: CA
authors.lastname: Loffredo
authors.forename: R
authors.initials: R
authors.lastname: Clarke
authors.forename: H
authors.initials: H
authors.lastname: Amri
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000601:surgery; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D010802:Phylogeny; D012016:Reference Values; D049490:Systems Biology / Q000379:methods*
references.citation: Int J Cancer. 2008 Apr 1;122(7):1557-66
references.pmid: 18058819
references.citation: Am J Med. 2007 Apr;120(4 Suppl 1):S21-5
references.pmid: 17403378
references.citation: OMICS. 2008 Sep;12(3):183-99
references.pmid: 18699725
references.citation: Nat Rev Cancer. 2008 Jan;8(1):37-49
references.pmid: 18097463
references.citation: Proteomics Clin Appl. 2008 Feb;2(2):122-134
references.pmid: 18458745
references.citation: Genomics. 2011 Oct;98(4):242-52
references.pmid: 21640814
references.citation: J Clin Oncol. 2008 Feb 20;26(6):995-1005
references.pmid: 18195328
references.citation: Breast Cancer Res Treat. 2010 Jan;119(2):335-46
references.pmid: 19266279
references.citation: Proc Natl Acad Sci U S A. 2010 Oct 26;107(43):18545-50
references.pmid: 20876136
references.citation: Adv Cancer Res. 2011;112:217-53
references.pmid: 21925306
references.citation: J Proteome Res. 2006 Sep;5(9):2236-40
references.pmid: 16944935
references.citation: BMC Bioinformatics. 2004 Aug 12;5:110
references.pmid: 15307894
references.citation: Nature. 2011 Mar 24;471(7339):428-32
references.pmid: 21430749
references.citation: Cancer Res. 2008 May 15;68(10):3551-7; discussion 3557
references.pmid: 18483233
references.citation: Front Oncol. 2011 Oct 17;1:33
references.pmid: 22649761
references.citation: Cancer Prev Res (Phila). 2010 Nov;3(11):1361-4
references.pmid: 20959519
references.citation: OMICS. 2011 Mar;15(3):105-12
references.pmid: 21319991
references.citation: Curr Drug Targets. 2010 Oct;11(10):1304-16
references.pmid: 20840073
references.citation: Toxicol Mech Methods. 2011 May;21(4):289-97
references.pmid: 21495867
references.citation: Nanomedicine (Lond). 2008 Apr;3(2):137-40
references.pmid: 18373419
references.citation: J Cell Physiol. 2009 Sep;220(3):538-47
references.pmid: 19441078
references.citation: Cancer Metastasis Rev. 1983;2(1):5-23
references.pmid: 6616442
references.citation: Exp Oncol. 2010 Sep;32(3):132-6
references.pmid: 21403606
references.citation: Cancer Epidemiol Biomarkers Prev. 1995 Apr-May;4(3):223-31
references.pmid: 7606196
references.citation: Cold Spring Harb Symp Quant Biol. 2008;73:171-4
references.pmid: 19150965
references.citation: J Natl Cancer Inst. 2010 Oct 6;102(19):1462-7
references.pmid: 20705936
references.citation: Breast Cancer Res Treat. 2011 Jul;128(2):327-36
references.pmid: 20697806
references.citation: Br J Cancer. 2010 Apr 13;102(8):1284-93
references.pmid: 20197764
references.citation: Science. 2011 Sep 16;333(6049):1569-71
references.pmid: 21921174