Ancestral inference in tumors: how much can we know?
J Theor Biol
; 359: 136-45, 2014 Oct 21.
Article
en En
| MEDLINE
| ID: mdl-24907673
ABSTRACT
A tumor is thought to start from a single cell and genome. Yet genomes in the final tumor are typically heterogeneous. The mystery of this intratumoral heterogeneity (ITH) has not yet been uncovered, but much of this ITH may be secondary to replication errors. Methylation of cytosine bases often exhibits ITH and therefore may encode the ancestry of the tumor. In this study, we measure the passenger methylation patterns of a specific CpG region in 9 colorectal tumors by bisulfite sequencing and apply a tumor development model. Based on our model, we are able to retrieve information regarding the ancestry of each tumor using approximate Bayesian computation. With a large simulation study we explore the conditions under which we can estimate the model parameters, and the initial state of the first transformed cell. Finally we apply our analysis to clinical data to gain insight into the dynamics of tumor formation.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Evolución Molecular
/
Biología Computacional
/
Neoplasias
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Año:
2014
Tipo del documento:
Article