It’s a real ‘data’s goldmine’, which today the researchers of Michelangelo Foundation and Gianni Bonadonna Foundation are drawing on: the METABRIC case series of breast cancer patients is the largest to have been widely characterized at the molecular level and is therefore a source of valuable information, generated by Prof. Caldas lab and collaborators at the Cancer Research UK Cambridge Institute. It is one of the largest cohorts where the recently developed Imaging Mass Cytometry (IMC) technology has been successfully applied to study the spatial organization and heterogeneity of both the tumour and its microenvironment at single cell resolution. Through a fruitful collaboration with Cambridge, IMC is now being used on patients enrolled in clinical studies designed and conducted by the Michelangelo Foundation.
«METABRIC is the largest breast cancer cohort including about two thousand patients for which up to 20 years of clinical information have been collected and a multi-dimensional molecular characterization has been generated. As a comparison, in The Cancer Genome Atlas, a landmark cancer genomics international program, there are many more tumour types included, but for breast cancer, samples from only a thousand cases are included», explains Maurizio Callari, Computational Biologist for Michelangelo Foundation and Gianni Bonadonna Foundation. Callari knows METABRIC very well because he worked for seven years at the Cancer Research UK Cambridge Institute in Prof. Caldas’ lab, where the cases were collected, characterized and gene expression and genomic profiles have been obtained. «The resulting datasets have always been made public and are also accessible through cBioPortal», Callari says. «The gene expression and copy number profiling of the METABRIC cohort was primarily used to identify and validate eleven breast cancer subtypes different for molecular characteristics and survival rates. Subsequently, the microRNA profiles have been generated, followed by the identification of somatic mutations in a panel of cancer genes. More recently, two studies reporting on the IMC and DNA methylation profiling have been reported. We know a lot about these samples and we can use them to evaluate the role of a target gene or to develop more complex and subtype-specific survival prediction models».
The IMC method, developed and applied by Dr. Raza Ali on METABRIC, is proving useful for Michelangelo Foundation and Gianni Bonadonna Foundation research: «We are collaborating with Raza to obtain similar data on patients enrolled in trials from the Foundation, to understand how this type of analysis can help to identify the mechanisms of response and therapeutic resistance in a specific clinical context», adds Callari. The first results of this collaboration will be presented during the upcoming San Antonio Breast Cancer Symposium.
