| Title: | Study of the genetic basis of clonal hematopoiesis |
| Lead Institution: | Institute for Research Biomedicine (IRB Barcelona) |
| Principal investigator: | Dr Nuria Lopez-Bigas |
Application 69794
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About
Clonal hematopoiesis is a prevalent condition across human populations, known to be related to aging and to the exposure to certain carcinogens, such as chemotherapies. It increases the risk of diseases such as cardiovascular ailments and hematopoietic malignancies. Therefore, accurately identifying clonal hematopoiesis in human subjects and understanding all the factors involved in its development are of paramount importance. Somatic mutations affecting certain genes of hematopoietic stem cells which provide certain advantages to the mutant cells in the face of evolutionary constraints are known to underlie the development of most clonal hematopoiesis cases. Moreover, mutations in different genes are known to underlie age-related clonal hematopoiesis and the condition arising from exposure to carcinogenic agents. However, to date only one or two dozen of the most frequently mutated among these clonal hematopoiesis driver genes have been recognized. This has hindered the two aforementioned goals, i.e., accurate identification of clonal hematopoiesis cases and the study of its underlying molecular mechanisms. We have recently repurposed large cohorts of blood samples taken from cancer patients as part of their diagnoses for the construction of the first unbiased snapshot of the compendium of clonal hematopoiesis driver genes. In this project we propose to apply the most up-to-date snapshot of said compendium to improve the sensitivity and specificity of the detection of cases of clonal hematopoiesis across the UK Biobank cohort. The results will serve as proof-of-concept for the design of an easy-to-use targeted sequencing panel for the accurate detection of clonal hematopoiesis associated with the general clinical practice. We will also study the different evolutionary constraints associated with mutations in different clonal hematopoiesis drivers to understand the influence of lifestyle exposure on the evolutionary constraints faced by hematopoietic stem cells that trigger the development of clonal hematopoiesis. This in turn will be important to predict the risk of certain individuals to develop the conditions associated with clonal hematopoiesis.1 Publication
| Pub ID | Title | Author(s) | Year | Journal |
|---|---|---|---|---|
| 12115 | Identification of Clonal Hematopoiesis Driver Mutations through In Silico Saturation Mutagenesis. | Santiago Demajo (+6) | 2024 | Cancer Discovery |
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