One of the goals of the research group is to continue our work on familial cancers using the modern large-scale NGS technologies. By performing whole exome sequencing in patients with familial cancers, that tested negative for mutations in BRCA1/2 and MMR-related genes, we plan to identify pathogenic mutations and set of genes contributing to the most common familial type of cancers, such as hereditary breast and ovarian, prostate, colorectal and other rare familial types of cancer in the Bulgarian population.
Cancer, as other complex traits, is polygenic. Genome-wide association studies (GWASs) have identified hundreds of independent cancer susceptibility loci containing common, low-risk variants. Estimation of heritability due to additive effects of all single-nucleotide polymorphisms (SNPs) included in GWAS arrays shows that common variants have substantial potential to identify individuals at different levels of risk for many cancer types. The accumulation of whole exome and genome data from Bulgarian cancer patients, coupled with genome data from healthy people in the frame of other research initiatives such as Genome of Europe, 1+M genomes, and PRACTICAL consortium, will allow us to investigate the use of polygenic risk scores to guide cancer screening and prevention strategies with the aim of implementing them on a national scale in the future.
The ongoing collaboration of Molecualr Medicine Center with leading university clinics of surgery and the establishment in our biobank of collections of different types of fresh frozen tumors will give us the possibility to upply a multi-omics approach to study the specific molecular characteristics of various solid tiumours. We aim to apply whole exome sequencing in search of somatic mutations and to couple it with whole transcriptome and methylation profiling into a combined system biology analysis. This approach will be applied on different solid tumours to provide better molecular subclasification and diagnostics, but also to identify tumour specific markers and potential therapeutic targets.
The molecular heterogeneity of cancer is one of the major causes of drug resistance that leads to treatment failure. To understand better the heterogeneity of cancer and the role of microenvironment we aim to apply spatial transcriptomics. Recently single-cell sequencing has become an important tool for investigating tumor heterogeneity, however, it misses the spatial information of the analyzed cells. By using spatial transcriptomics and providing localization-indexed gene expression information we aim to study the nature of both inter-tumour and intra-tumor heterogeneity, tumor immune microenvironment, and matrix microenvironment, as well as the pathological classification and prognosis of cancer.