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FRIMEDBIO-Fri prosj.st. med.,helse,biol

Multiple breast malignancies in dogs; improved understanding of disease progression by human-canine comparison

Alternative title: Multiple jursvulster hos hund – Kan sammenlikning av brystkreft hos menneske og hund bidra til ny kunnskap om kreftutvikling?

Awarded: NOK 9.2 mill.

Breast cancer is the most common cancer in dogs and humans. Mammary gland tumors in dogs and humans are remarkably similar at several levels: Clinically, morphologically and molecularly, and there is a great potential in comparative studies that can benefit both dogs and humans suffering from breast cancer. The genetic makeup of the two species are highly similar, but there is a need for more knowledge of the genetic similarities of mammary gland tumors in dogs and humans. There are major differences in the incidence of breast cancer between dog breeds, indicating a significant heritable component with accumulation of risk alleles within some breeds. Breast cancer cases from high-risk breeds therefore provide excellent models that may contribute to improved understanding of breast cancer progression. The project group will use unique samples and state of the art methods for the study of risk factors and mechanisms of tumor progression. Multiple tumors, which are common in dogs but seldom in human, provides a suitable opportunity to study pairs of tumors with similar or different morphological classification, including genetic variants/mutations, differential gene expression profiles, molecular subtypes and cellular microenvironment. The project group also aims to study natural progression of breast cancer in dogs and provide longitudinal series of repeated samples from morphologically classified tumors including tumors that transition from benign to malignant. This provides a unique opportunity for mapping genetic changes throughout progression. The interdisciplinary collaboration will be important for discovering new mechanisms that may contribute to improved precision medicine in both dogs and humans.

Breast cancer is the most common cancer in dogs and the second leading cause of cancer related death among women. Dogs have basically the same morphological breast tumor types and similar clinical and morphological diagnostic methods are used. Dogs and humans are exposed to many of the same environmental risk factors since they are living together in the same household and partly share some food ingredients. The incidence of breast cancer is significantly different between dog breeds, indicating an accumulation of risk alleles within some breeds. The genomes of the two species have a high similarity, but with much longer LD and much lower genetic heterogeneity within dog breeds compared to human populations. Breast cancer cases from high risk breeds therefore provide excellent models that may contribute important information for improved understanding of breast cancer progression. The project group will use two unique materials and state of the art methods for the study of risk factors and mechanisms in tumor progression. A material of synchronous tumors provides a suitable opportunity to study pairs of tumors with similar or different morphological classification, including genetic variants/mutations, differential expression, molecular subtypes and microenvironment. The Project group already have collected a high number of samples (DNA/RNA from germline and tumor) from dog with multiple tumors. The second material is from a project following natural progression of breast cancer in old dogs and provide longitudinal series of repeated samples from morphologically classified tumors including tumors with transition from benign to malignant classification. This material provides a unique opportunity to study somatic mutations, expression profiles, molecular subtypes and microenvironment in tumors throughout progression. The interdisciplinary collaboration will be important to discovered new mechanisms that may contribute to improve precision medicine in dogs and human.

Funding scheme:

FRIMEDBIO-Fri prosj.st. med.,helse,biol

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