DiSsecting fetal genetiC and epigenetic changes After in utero exposure to chemotheRapy

ended

Cancer complicates 1 in 1000 pregnancies representing an important health challenge that affects both mother and child. In a series of breakthrough clinical studies, the hosting lab has shown that chemotherapy given during pregnancy is relatively safe for the infants in the short term. However, children born after in utero exposure to chemotherapy are often small for their gestation age, present with lower IQ scores and have higher risk to wear glasses, suggesting possible long-term health effects. Because chemotherapy elicits (epi)genetic alterations to cancer patients, we hypothesize that chemotherapy-mediated long-term health effects could be due to (epi)genetic changes in the offspring of women treated with chemotherapy during pregnancy. Thus, SCAR aims to determine whether in utero exposure to carboplatin may be linked to DNA damage in the offspring. My objectives are to 1) identify the genetic damage at single cell level and 2) determine epigenetic modifications; in umbilical cord blood cells of children in utero exposed to carboplatin. To this end, I will integrate highly innovative sequencing techniques and the access of the hosting team to a unique registry of pregnant cancer patients. As the phenotypic expression of these genetic alterations could take decades to appear, studying the underlying molecular epi(genetic) changes at birth, will provide more immediate evidence than long-term clinical follow-up, and will be instrumental to define safe and solid treatment guidelines for pregnant cancer patients. Through this work, I aim to broaden my scientific expertise (including technical and transferable skills) and my international network for pursuing an academic career in Europe. The MSCA-IF will be instrumental to actualize many objectives outlined in my career development plan in order to become an independent researcher in the genetic oncology field.