Cancer driver genes can undergo positive selection for various types of genetic alterations, including gain-of-function or loss-of-function mutations and copy number alterations (CNA). We investigated the landscape of different types of alterations affecting driver genes in 17,644 cancer exomes and genomes. We find that oncogenes may simultaneously exhibit signatures of positive selection and also negative selection in different gene segments, suggesting a method to identify additional tumor types where an oncogene is a driver or a vulnerability. Next, we characterize the landscape of CNA-dependent selection effects, revealing a general trend of increased positive selection on oncogene mutations not only upon CNA gains but also upon CNA deletions. Similarly, we observe a positive interaction between mutations and CNA gains in tumor suppressor genes. Thus, two-hit events involving point mutations and CNA are universally observed regardless of the type of CNA and may signal new therapeutic opportunities. An analysis with focus on the somatic CNA two-hit events can help identify additional driver genes relevant to a tumor type. By a global inference of point mutation and CNA selection signatures and interactions thereof across genes and tissues, we identify 9 evolutionary archetypes of driver genes, representing different mechanisms of (in)activation by genetic alterations.
Publications
Website LinkThis report summarises the Policy brief formulating recommendations based on the research and innovation strand of the “Understanding” annual cluster meeting, M12. The goal of this deliverable is to provide an annual policy brief with recommendations on R&I on the macro scale, i.e., from the perspective of “Understanding (risk factors and determinants) cluster.
This policy brief formulates recommendations to foster collaboration, focusing on data/material management, technological advancements, risk factor analysis, and policy implementation, based on the research and innovation strand of the “Understanding” annual cluster meeting, M12. This deliverable raises common barriers and potential recommendations as well as practical recommendations for the near future.
This newsletter provides an update about the project activities.
This deliverable has been conceived in the frame of T4.2 “Clinical protocols and requirements”, which is devolted to the organization of the assessment methodology that will be implemented during the development of each use-case at different levels after risk stratification of citizens and clinical scenario. All the designs will be based on the feedback and results after of tasks developed in WP3 and WP5. The following actions will be deployed:
– developing and agreeing on the sampling plan;
– choosing and testing measurement instruments;
– choosing the early diagnosis clinical pathways;
– choosing the diagnosis workflow; and
– planning the data collection and the validation protocols.
After the protocol design (which has already been finalized), all the authorizations required by the regulatory authorities will be obtained.
This deliverable provides the essential regulatory and research documents for the beginning and development of Task 4.3: “General population screening” under which the prospective clinical study will start recruiting participants and gathering data for the LUCIA project.
The content of this deliverable summarizes the clinical protocol for the cohort study in the general population screening and the regulatory authorizations that must be obtained before the enrollment of the first participant in the study.
This deliverable includes the following information:
– Final version of the study protocols of each clinical site as sent to each one of their respective ethics committees.
– Regulatory authorizations required for the enrolment of the first study participant.
The consortium partners have finalized and agreed on the common prospective clinical protocol, which ensures we reach the highest standards of quality and clinical and scientific relevance. The protocols have already been submitted to each one of the Ethics Committees for its approval request in December 2023.
We foresee to obtain the approval of the Ethics Committees in the coming months and start the recruitment of the volunteers that will participate in the prospective clinical study as soon as we get those approvals.
Since the approval has not been obtained yet, we provide in this document the documents of Request for Evaluation of research projects by the Ethics Committees of each clinical site until we obtain the approvals. Once we get them, we will provide also these regulatory authorizations.
This deliverable has been conceived in the frame of T4.2 “Clinical protocols and requirements”, which is devolted to the organization of the assessment methodology that will be implemented during the development of each use-case at different levels after risk stratification of citizens and clinical scenario. All the designs will be based on the feedback and results after of tasks developed in WP3 and WP5. The following actions will be deployed:
– developing and agreeing on the sampling plan;
– choosing and testing measurement instruments;
– choosing the early diagnosis clinical pathways;
– choosing the diagnosis workflow; and
– planning the data collection and the validation protocols.
After the protocol design (which has already been finalized), all the authorizations required by the regulatory authorities will be obtained.
This deliverable provides the essential regulatory and research documents for the beginning and development of Task 4.3: “General population screening” under which the prospective clinical study will start recruiting participants and gathering data for the LUCIA project.
The content of this deliverable summarizes the clinical protocol for the cohort study in the general population screening and the regulatory authorizations that must be obtained before the enrollment of the first participant in the study.
This deliverable includes the following information:
– Final version of the study protocols of each clinical site as sent to each one of their respective ethics committees.
– Regulatory authorizations required for the enrolment of the first study participant.
The consortium partners have finalized and agreed on the common prospective clinical protocol, which ensures we reach the highest standards of quality and clinical and scientific relevance. The protocols have already been submitted to each one of the Ethics Committees for its approval request in December 2023.
We foresee to obtain the approval of the Ethics Committees in the coming months and start the recruitment of the volunteers that will participate in the prospective clinical study as soon as we get those approvals.
Since the approval has not been obtained yet, we provide in this document the documents of Request for Evaluation of research projects by the Ethics Committees of each clinical site until we obtain the approvals. Once we get them, we will provide also these regulatory authorizations.
