Understanding the genetics of cancer

English version of the article published in UNIL-L'ACTU on 06.04.2018

In order to develop personalized treatments for cancer therapy, it is imperative to embark on the daunting task of understanding the extent, detailed mechanisms, and co-occurrence of molecular alterations underlying the emergence and progression of each patient’s disease. Indeed, highly heterogeneous combinations of alterations characterize human tumors, including molecular changes selectively observed in specific tumor types and others ubiquitously present independent of the tissue of origin.

 

Started in 2005, The Cancer Genome Atlas (TCGA) Consortium started tackling this challenge by collecting and profiling thousands of human cancers, with the aim of genomically characterize each tumor. Today, a joint effort of the research group led by Giovanni Ciriello at the University of Lausanne and collaborators from the Memorial Sloan Kettering Cancer Center in New York and Dana Farber Cancer Institute in Boston released an accurate and comprehensive compendium of the alterations affecting the most important signaling pathways in cancer. The study, published in Cell, is most comprehensive to date pan-cancer exploration of similarities and differences among alterations affecting ~9,000 human tumors from 33 different types of cancer.

 

The authors curated more than 400 types of cancer alterations and their effect on specific genes and cellular processes. Moreover,  treatment opportunities for the analyzed patients have been explored based on currently available therapeutic agents and the specific set of alterations found in each tumor. Moving one step forward, the authors explored which combinations of alterations are frequently observed across patients, revealing concurrent and synergistic activation of specific pathways and, importantly, pinpointing candidate combination treatments. This work builds on methodological advancements that the research unit of Prof. Ciriello has developed to dissect the complex interplay of co-occurring and mutually exclusive alterations within and among pathways and alterations.

 

“This landscape of alterations of signaling pathways is meant to provide a valuable resource for clinical oncologists, cancer researchers, and for a broad scientific community interested in cancer precision medicine” says Dr. Marco Mina, one of the lead authors of the study, and senior post-doc in the group of Prof. Ciriello. While a lot remains to be done, comprehensively mapping oncogenic alterations to patient groups and treatments options is a crucial first step to implement personalized medicine in cancer care.

 

This manuscript is part of The Cancer Genome Atlas ( TCGA) Program, a joint effort of the National Cancer Institute (NCI ) and the National Human Genome Research Institute (NHGRI).

 

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