title: A differentiation-based phylogeny of cancer subtypes.
abstract: Histopathological classification of human tumors relies in part on the degree of differentiation of the tumor sample. To date, there is no objective systematic method to categorize tumor subtypes by maturation. In this paper, we introduce a novel computational algorithm to rank tumor subtypes according to the dissimilarity of their gene expression from that of stem cells and fully differentiated tissue, and thereby construct a phylogenetic tree of cancer. We validate our methodology with expression data of leukemia, breast cancer and liposarcoma subtypes and then apply it to a broader group of sarcomas. This ranking of tumor subtypes resulting from the application of our methodology allows the identification of genes correlated with differentiation and may help to identify novel therapeutic targets. Our algorithm represents the first phylogeny-based tool to analyze the differentiation status of human tumors.
authors.affiliation: Computational Biology Center, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: Markus
authors.initials: M
authors.lastname: Riester
authors.forename: Camille
authors.initials: C
authors.lastname: Stephan-Otto Attolini
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Downey
authors.forename: Samuel
authors.initials: S
authors.lastname: Singer
authors.forename: Franziska
authors.initials: F
authors.lastname: Michor
mesh_terms: D050156:Adipogenesis / Q000235:genetics; D000465:Algorithms; D000704:Analysis of Variance; D002454:Cell Differentiation / Q000502:physiology; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009369:Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology; D010802:Phylogeny
references.citation: Leuk Res. 1985;9(2):191-8
references.pmid: 3857408
references.citation: Biostatistics. 2003 Apr;4(2):249-64
references.pmid: 12925520
references.citation: Clin Cancer Res. 2007 Jun 1;13(11):3207-14
references.pmid: 17545524
references.citation: Genome Biol. 2004;5(10):R80
references.pmid: 15461798
references.citation: Ann Surg Oncol. 2004 Jan;11(1):78-84
references.pmid: 14699038
references.citation: Cancer Res. 2007 Jul 15;67(14):6626-36
references.pmid: 17638873
references.citation: Bioinformatics. 2002 Apr;18(4):536-45
references.pmid: 12016051
references.citation: Br J Haematol. 1976 Aug;33(4):451-8
references.pmid: 188440
references.citation: Int J Cancer. 2008 Apr 1;122(7):1557-66
references.pmid: 18058819
references.citation: Leukemia. 2005 Mar;19(3):402-9
references.pmid: 15674361
references.citation: J Natl Cancer Inst. 2006 Feb 15;98(4):262-72
references.pmid: 16478745
references.citation: Mod Pathol. 2007 Jul;20(7):749-59
references.pmid: 17464315
references.citation: Bioinformatics. 2006 Apr 15;22(8):1010-2
references.pmid: 16500939
references.citation: Proc Natl Acad Sci U S A. 2005 Sep 20;102(38):13550-5
references.pmid: 16141321
references.citation: J Comput Biol. 1999 Spring;6(1):37-51
references.pmid: 10223663
references.citation: Cancer. 1980 Dec 15;46(12 Suppl):2884-8
references.pmid: 7448733
references.citation: Am J Pathol. 2008 Apr;172(4):1069-80
references.pmid: 18310505
references.citation: Nat Rev Cancer. 2006 Dec;6(12):924-35
references.pmid: 17109012
references.citation: Proc Natl Acad Sci U S A. 2004 Mar 2;101(9):2957-62
references.pmid: 14976249
references.citation: J Bioinform Comput Biol. 2005 Aug;3(4):965-88
references.pmid: 16078370
references.citation: Mol Biol Evol. 2002 Oct;19(10):1769-81
references.pmid: 12270903
references.citation: Mol Biol Evol. 1993 Sep;10(5):1073-95
references.pmid: 8412650
references.citation: Genome Inform Ser Workshop Genome Inform. 2000;11:129-40
references.pmid: 11700594
references.citation: Cancer Genet Cytogenet. 2004 Nov;155(1):1-24
references.pmid: 15527898
references.citation: Blood. 2008 Nov 15;112(10):4193-201
references.pmid: 18716133
references.citation: IEEE/ACM Trans Comput Biol Bioinform. 2009 Apr-Jun;6(2):200-12
references.pmid: 19407345
references.citation: Genes Chromosomes Cancer. 2008 Jan;47(1):8-20
references.pmid: 17910043
references.citation: Nat Rev Cancer. 2003 Feb;3(2):89-101
references.pmid: 12563308
references.citation: Nat Rev Cancer. 2004 Mar;4(3):197-205
references.pmid: 14993901
references.citation: Stem Cells. 2006 Aug;24(8):1956-67
references.pmid: 16675594
references.citation: Mol Biol Evol. 1987 Jul;4(4):406-25
references.pmid: 3447015
references.citation: BMC Genomics. 2006 Sep 11;7:231
references.pmid: 16965636
references.citation: Nature. 1968 Feb 17;217(5129):624-6
references.pmid: 5637732
references.citation: J Bone Miner Res. 2004 Feb;19(2):256-64
references.pmid: 14969395
references.citation: Mol Biol Evol. 2004 Jul;21(7):1459-61
references.pmid: 15084681
references.citation: BMC Bioinformatics. 2007 Nov 22;8:460
references.pmid: 18034891
references.citation: Ann Surg. 2006 Sep;244(3):381-91
references.pmid: 16926564
references.citation: Exp Biol Med (Maywood). 2001 Jun;226(6):507-20
references.pmid: 11395921
references.citation: BMC Cancer. 2003 Apr 24;3:13
references.pmid: 12713671
references.citation: J Comput Biol. 2000;7(6):789-803
references.pmid: 11382362
references.citation: J Comput Biol. 2005 Jul-Aug;12(6):584-98
references.pmid: 16108705
references.citation: Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):14863-8
references.pmid: 9843981
references.citation: Mol Biol Evol. 2000 Jan;17(1):189-97
references.pmid: 10666718
references.citation: Biostatistics. 2004 Oct;5(4):545-56
references.pmid: 15475418
references.citation: Nucleic Acids Res. 2007 Jan;35(Database issue):D760-5
references.pmid: 17099226
references.citation: Mol Biol Evol. 2004 Mar;21(3):587-98
references.pmid: 14694080
references.citation: Nat Genet. 2010 Aug;42(8):715-21
references.pmid: 20601955
references.citation: Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):2907-12
references.pmid: 10077610
references.citation: Cell. 2000 Jan 7;100(1):57-70
references.pmid: 10647931
references.citation: Science. 1967 Jan 20;155(3760):279-84
references.pmid: 5334057
references.citation: Science. 1999 Oct 15;286(5439):531-7
references.pmid: 10521349
references.citation: Cancer. 1995 Jan 1;75(1 Suppl):211-44
references.pmid: 8000998
references.citation: Mol Biol Evol. 1994 May;11(3):459-68
references.pmid: 8015439
references.citation: Ann Surg. 2003 Sep;238(3):358-70; discussion 370-1
references.pmid: 14501502
references.citation: Bioinformatics. 2003 Jan 22;19(2):185-93
references.pmid: 12538238
references.citation: J Theor Biol. 2004 Jun 21;228(4):477-96
references.pmid: 15178197
references.citation: Nat Med. 2007 May;13(5):642-8
references.pmid: 17417652
references.citation: Genome Res. 2001 Jul;11(7):1149-55
references.pmid: 11435396