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A Cascade of Modules of a Network Defines Cancer Progression

Departments of Medicine (Genetics Program and Cancer Research Center), Genetics and Genomics, and Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, Massachusetts

Requests for reprints: Sam Thiagalingam, Genetics Program, Boston University School of Medicine, 715 Albany Street, L320, Boston, MA 02118. Phone: 617-638-6013; Fax: 617-638-4275; E-mail: samthia{at}bu.edu.

Abstract

Similar histologic subtypes of cancers often exhibit different spectrum of genetic and epigenetic alterations. The heterogeneity observed due to lack of consistent and defined alterations affecting a unique set of gene(s) or gene products in cancers derived from a specific tissue, or an organ, pose a challenge in unraveling the molecular basis of the disease. This dilemma also complicates diagnosis, prognosis, effective management, and treatment modalities. To streamline the available and emerging data into a coherent scheme of events, a multimodular molecular network (MMMN) cancer progression model is presented as a roadmap to dissect the complexity inherent to this disease. The fact that disruption/dysregulation of more than one alternate target gene could affect the functionality of each specific module of a cascade provides a molecular basis for genetic and epigenetic heterogeneity in any given cancer. Polymorphisms/mutations as well as the extracellular matrix and or the epigenetically/genetically conditioned surrounding stromal cells could also influence the rate of tumorigenesis and the properties of the tumor cells. The formulation of MMMN cancer progression models for specific cancers is likely to provide the blueprints for the markers and targets to aid diagnosis, prevention, and therapy of this deadly disease. (Cancer Res 2006; 66(15): 7379-85)