Cancer progression in humans is difficult to infer because we do not routinely sample patients at multiple stages of their disease. However, heterogeneous breast tumors provide a unique opportunity to study human tumor progression because they still contain evidence of early and intermediate subpopulations in the form of the phylogenetic relationships. We have developed a method we call Sector-Ploidy-Profiling (SPP) to study the clonal composition of breast tumors. SPP involves macro-dissecting tumors, flow-sorting genomic subpopulations by DNA content, and profiling genomes using comparative genomic hybridization (CGH). Breast carcinomas display two classes of genomic structural variation: (1) monogenomic and (2) polygenomic. Monogenomic tumors appear to contain a single major clonal subpopulation with a highly stable chromosome structure. Polygenomic tumors contain multiple clonal tumor subpopulations, which may occupy the same sectors, or separate anatomic locations. In polygenomic tumors, we show that heterogeneity can be ascribed to a few clonal subpopulations, rather than a series of gradual intermediates. By comparing multiple subpopulations from different anatomic locations, we have inferred pathways of cancer progression and the organization of tumor growth.
Inferring tumor progression from genomic heterogeneity.
N. Navin,A. Krasnitz,L. Rodgers,K. Cook,J. Meth,J. Kendall,M. Riggs,Y. Eberling,J. Troge,V. Grubor,D. Levy,P. Lundin,S. Månér,A. Zetterberg,J. Hicks,M. Wigler
Published 2010 in Genome Research
ABSTRACT
PUBLICATION RECORD
- Publication year
2010
- Venue
Genome Research
- Publication date
Unknown publication date
- Fields of study
Biology, Medicine
- Identifiers
- External record
- Source metadata
Semantic Scholar, PubMed
CITATION MAP
EXTRACTION MAP
CLAIMS
CONCEPTS
- anatomic locations
Distinct physical regions within a tumor that can be sampled and compared.
Aliases: tumor sectors, locations
- breast carcinomas
Malignant epithelial tumors of the breast examined as the disease context in the abstract.
Aliases: breast cancer tumors
- cancer progression pathways
The inferred lineage routes by which tumor clones arise and diverge over time.
Aliases: progression pathways
- chromosome structure
The arrangement and stability of chromosomes within a tumor cell population.
Aliases: chromosomal structure
- clonal composition
The mixture and relative organization of tumor cell clones within a cancer sample.
Aliases: clone composition
- clonal subpopulation
A group of tumor cells sharing a common clonal origin and genomic profile.
Aliases: clone, clonal lineage
- clonal tumor subpopulations
Distinct tumor-derived clonal groups present within a polygenomic cancer.
Aliases: tumor clones
- comparative genomic hybridization
A genome profiling technique used to detect copy-number differences across tumor DNA samples.
Aliases: CGH
- flow sorting
A cell-separation procedure that isolates genomic subpopulations based on DNA content.
Aliases: flow-sorting
- genomic structural variation
Differences in chromosome-level genomic structure used here to classify tumor organization.
Aliases: structural variation
- monogenomic tumors
Tumors characterized by a largely single genomic lineage with limited structural diversity.
Aliases: monogenomic breast tumors
- polygenomic tumors
Tumors composed of multiple genomic lineages within the same cancer mass.
Aliases: polygenomic breast tumors
- sector-ploidy-profiling (spp)
A tumor-profiling strategy that uses sector sampling, DNA-content sorting, and genome profiling to examine clonal structure.
Aliases: SPP, Sector-Ploidy-Profiling
- tumor growth organization
The spatial and clonal arrangement of tumor expansion within the tissue.
Aliases: organization of tumor growth
- tumor heterogeneity
Variation in genomic or clonal makeup among cells within the same tumor.
Aliases: intratumor heterogeneity
REFERENCES
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