Computational oncology and personalized medicine Priority Research Area POB1

We cordially invite everyone to participate in our next POB1 seminar. Our guest is Prof. Lajos Pusztai, the Director of Breast Cancer Translational Research from Yale Cancer Genetics and Genomics Program, Yale School of Medicine, New Haven, USA. Prof. Lajos Pusztai will held a lecture entitled “Cancer biology as a combinatorial challenge”. 

Meeting will be organized using Zoom platform.

Each cancer has a unique clinical course and behavior, and harbors hundreds of somatic genomic alterations in unique combinations. Most somatic alterations occur with low frequencies, and these are considered biologically inert “passenger mutations”. Increasingly, laboratory studies indicate that many of these passenger mutations have a functional impact on cell biology. All somatic alterations occur against the background of an even more diverse germline SNP repertoire. Variation in germline SNPs explains most of the human variation, proving their impact on biology. We hypothesize that the combination of both somatic mutations and germline variants affects cancer biology and collectively determine the unique course of each cancer. We recently demonstrated that high functional germline variants and low-frequency passenger mutations often map into canonical cancer biology pathways. On average, patients who develop cancer at a younger age have a higher germline variant burden in cancer hallmark genes and fewer acquired somatic mutations than those who develop cancer at an older age. However, the contribution of germline versus somatic alterations in cancer-relevant genes also varies by cancer type. We show that many human genes may have context-dependent cancer relevance inferred from their network connectivity. We acknowledge that different genes have different functional importance in malignant transformation but believe that the “cancer driver” versus “passenger mutation” dichotomization is a simplification. What counts as a driver event is context-dependent and understanding the malignant transformation process represents a combinatorial challenge of multiple hits from somatic and germline origins leading to a convergent phenotype (i.e cancer).