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IS-BILAT-Mobilitet Norge-USA /Canada

Molecular heterogeneity of breast carcinomas; clinical implication of tumor subclones.

Awarded: NOK 0.21 mill.

Breast carcinomas are considered a heterogeneous tumor type both at the clinical, pathological and molecular level, and individual tumors can display a wide range of molecular variation. Recent work separating tumor cells into subfractions based on differ entially expressed cell surface markers has proved the existence of subpopulations of tumor cells with either stem cell like or more differentiated features. Breast carcinomas can be subdivided into at least five different types based on alterations in ge ne expression. The subtypes are based on similarities in gene expression pattern, and have resemblance to patterns seen in breast epithelium cells at different levels and directions of differentiation. In previous studies we have seen that some of the sub types are closely related both to genomic aberrations and methylation patterns, while others display a more varied group of tumors. This post-doctoral project is aiming at exploring the molecular heterogeneity within individual tumors with relation to di fferentiation and clinical parameters. Complex rearrangements of the tumor genome will be studied more closely both to reveal potential tumor-specific markers such as fusion genes and to search for genes that can be used as targets for therapy. The studie s will be performed both by high resolution techniques on sorted cell populations, tumorextracts and by functional studies of cells in culture. Findings of interest will be validated in larger clinical cohorts. Cultivated tumor cells will in addition be g rown under different conditions to study epitumoral influences on cellular differentiation. Differentiation is a well established prognostic marker, and inducing differentiation by restoring genomic defects that has haltered the process is a successful tr eatment for instances in a subtype of leukemia. Several of the techniques are not available in Norway at the moment.

Funding scheme:

IS-BILAT-Mobilitet Norge-USA /Canada