title: Cell lineage analysis of a mouse tumor.
abstract: Revealing the lineage relations among cancer cells can shed light on tumor growth patterns and metastasis formation, yet cell lineages have been difficult to come by in the absence of a suitable method. We previously developed a method for reconstructing cell lineage trees from genomic variability caused by somatic mutations. Here, we apply the method to cancer and reconstruct, for the first time, a lineage tree of neoplastic and adjacent normal cells obtained by laser microdissection from tissue sections of a mouse lymphoma. Analysis of the reconstructed tree reveals that the tumor initiated from a single founder cell, approximately 5 months before diagnosis, that the tumor grew in a physically coherent manner, and that the average number of cell divisions accumulated in cancerous cells was almost twice than in adjacent normal lung epithelial cells but slightly less than the expected figure for normal B lymphocytes. The cells were also genotyped at the TP53 locus, and neoplastic cells were found to share a common mutation, which was most likely present in a heterozygous state. Our work shows that the ability to obtain data regarding the physical appearance, precise anatomic position, genotypic profile, and lineage position of single cells may be useful for investigating cancer development, progression, and interaction with the microenvironment.
authors.affiliation: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Dan
authors.initials: D
authors.lastname: Frumkin
authors.forename: Adam
authors.initials: A
authors.lastname: Wasserstrom
authors.forename: Shalev
authors.initials: S
authors.lastname: Itzkovitz
authors.forename: Tomer
authors.initials: T
authors.lastname: Stern
authors.forename: Alon
authors.initials: A
authors.lastname: Harmelin
authors.forename: Raya
authors.initials: R
authors.lastname: Eilam
authors.forename: Gideon
authors.initials: G
authors.lastname: Rechavi
authors.forename: Ehud
authors.initials: E
authors.lastname: Shapiro
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000818:Animals; D019070:Cell Lineage; D049109:Cell Proliferation; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005838:Genotype; D006579:Heterozygote; D008223:Lymphoma / Q000235:genetics / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D000070957:MutL Protein Homolog 1; D009154:Mutation; D009369:Neoplasms / Q000235:genetics / Q000473:pathology*; D009687:Nuclear Proteins / Q000235:genetics; D010802:Phylogeny
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C501485:Mlh1 protein, mouse; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1