Evaluating offspring Genomic and Epigenomic alterations after prenatal exposure to Cancer treatment In Pregnancy (GE-CIP): a multicentric observational study
Introduction Around 1 in 1000–2000 pregnancies are affected by a cancer diagnosis. Previous studies have shown that chemotherapy during pregnancy has reassuring cognitive and cardiac neonatal outcomes, and hence has been proposed as standard of care. However, although these children perform within n...
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BMJ Publishing Group
2024-03-01
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| Series: | BMJ Open |
| Online Access: | https://bmjopen.bmj.com/content/14/3/e081833.full |
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| author | Lode Godderis Bernard Thienpont Koenraad Devriendt Frédéric Amant Vera Wolters Liesbeth Lenaerts Kristel Van Calsteren Thierry Voet Ilana Struys Carolina Velázquez Heidi Segers Ruben van Boxtel |
| author_facet | Lode Godderis Bernard Thienpont Koenraad Devriendt Frédéric Amant Vera Wolters Liesbeth Lenaerts Kristel Van Calsteren Thierry Voet Ilana Struys Carolina Velázquez Heidi Segers Ruben van Boxtel |
| author_sort | Lode Godderis |
| collection | DOAJ |
| description | Introduction Around 1 in 1000–2000 pregnancies are affected by a cancer diagnosis. Previous studies have shown that chemotherapy during pregnancy has reassuring cognitive and cardiac neonatal outcomes, and hence has been proposed as standard of care. However, although these children perform within normal ranges for their age, subtle differences have been identified. Given that chemotherapeutic compounds can cross the placenta, the possibility that prenatal chemotherapy exposure mutates the offspring’s genome and/or epigenome, with potential deleterious effects later in life, urges to be investigated.Methods and analyses This multicentric observational study aims to collect cord blood, meconium and neonatal buccal cells at birth, as well as peripheral blood, buccal cells and urine from infants when 6, 18 and/or 36 months of age. Using bulk and single-cell approaches, we will compare samples from chemotherapy-treated pregnant patients with cancer, pregnant patients with cancer not treated with chemotherapy and healthy pregnant women. Potential chemotherapy-related newborn genomic and/or epigenomic alterations, such as single nucleotide variants, copy number variants and DNA-methylation alterations, will be identified in mononuclear and epithelial cells, isolated from blood, buccal swabs and urine. DNA from maternal peripheral blood and paternal buccal cells will be used to determine de novo somatic mutations in the neonatal blood and epithelial cells. Additionally, the accumulated exposure of the fetus, and biological effective dose of alkylating agents, will be assessed in meconium and cord blood via mass spectrometry approaches.Ethics and dissemination The Ethics Committee Research of UZ/KU Leuven (EC Research) and the Medical Ethical Review Committee of University Medical Center Amsterdam have approved the study. Results of this study will be disseminated via presentations at (inter)national conferences, through peer-reviewed, open-access publications, via social media platforms aimed to inform patients and healthcare workers, and through the website of the International Network on Cancer, Infertility and Pregnancy (www.cancerinpregnancy.org). |
| format | Article |
| id | doaj-art-d6098ada18d84dbe8816f8aacd440c2a |
| institution | DOAJ |
| issn | 2044-6055 |
| language | English |
| publishDate | 2024-03-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open |
| spelling | doaj-art-d6098ada18d84dbe8816f8aacd440c2a2025-08-20T03:11:36ZengBMJ Publishing GroupBMJ Open2044-60552024-03-0114310.1136/bmjopen-2023-081833Evaluating offspring Genomic and Epigenomic alterations after prenatal exposure to Cancer treatment In Pregnancy (GE-CIP): a multicentric observational studyLode Godderis0Bernard Thienpont1Koenraad Devriendt2Frédéric Amant3Vera Wolters4Liesbeth Lenaerts5Kristel Van Calsteren6Thierry Voet7Ilana Struys8Carolina Velázquez9Heidi Segers10Ruben van Boxtel112 Knowledge Information and Research Center, Group Idewe, Leuven, BelgiumDepartment of Human Genetics, KU Leuven, Leuven, Flanders, BelgiumDepartment of Human Genetics, University Hospital Leuven, Leuven, Belgium3Gynecologic Oncology, Center for Gynecologic Oncology Amsterdam, Amsterdam, NetherlandsGynecologic Oncology, Netherlands Cancer Institute, Amsterdam, NetherlandsDepartment of Oncology, KU Leuven, Leuven, Flanders, BelgiumDepartment of Obstetrics and Gynecology, University Hospital Leuven, Leuven, BelgiumDepartment of Human Genetics, KU Leuven, Leuven, Flanders, BelgiumDepartment of Oncology, KU Leuven, Leuven, Flanders, BelgiumDepartment of Oncology, KU Leuven, Leuven, Flanders, BelgiumDepartment of Paediatric Oncology, University Hospital Leuven, Leuven, BelgiumPrincess Maxima Center for Pediatric Oncology, Utrecht, NetherlandsIntroduction Around 1 in 1000–2000 pregnancies are affected by a cancer diagnosis. Previous studies have shown that chemotherapy during pregnancy has reassuring cognitive and cardiac neonatal outcomes, and hence has been proposed as standard of care. However, although these children perform within normal ranges for their age, subtle differences have been identified. Given that chemotherapeutic compounds can cross the placenta, the possibility that prenatal chemotherapy exposure mutates the offspring’s genome and/or epigenome, with potential deleterious effects later in life, urges to be investigated.Methods and analyses This multicentric observational study aims to collect cord blood, meconium and neonatal buccal cells at birth, as well as peripheral blood, buccal cells and urine from infants when 6, 18 and/or 36 months of age. Using bulk and single-cell approaches, we will compare samples from chemotherapy-treated pregnant patients with cancer, pregnant patients with cancer not treated with chemotherapy and healthy pregnant women. Potential chemotherapy-related newborn genomic and/or epigenomic alterations, such as single nucleotide variants, copy number variants and DNA-methylation alterations, will be identified in mononuclear and epithelial cells, isolated from blood, buccal swabs and urine. DNA from maternal peripheral blood and paternal buccal cells will be used to determine de novo somatic mutations in the neonatal blood and epithelial cells. Additionally, the accumulated exposure of the fetus, and biological effective dose of alkylating agents, will be assessed in meconium and cord blood via mass spectrometry approaches.Ethics and dissemination The Ethics Committee Research of UZ/KU Leuven (EC Research) and the Medical Ethical Review Committee of University Medical Center Amsterdam have approved the study. Results of this study will be disseminated via presentations at (inter)national conferences, through peer-reviewed, open-access publications, via social media platforms aimed to inform patients and healthcare workers, and through the website of the International Network on Cancer, Infertility and Pregnancy (www.cancerinpregnancy.org).https://bmjopen.bmj.com/content/14/3/e081833.full |
| spellingShingle | Lode Godderis Bernard Thienpont Koenraad Devriendt Frédéric Amant Vera Wolters Liesbeth Lenaerts Kristel Van Calsteren Thierry Voet Ilana Struys Carolina Velázquez Heidi Segers Ruben van Boxtel Evaluating offspring Genomic and Epigenomic alterations after prenatal exposure to Cancer treatment In Pregnancy (GE-CIP): a multicentric observational study BMJ Open |
| title | Evaluating offspring Genomic and Epigenomic alterations after prenatal exposure to Cancer treatment In Pregnancy (GE-CIP): a multicentric observational study |
| title_full | Evaluating offspring Genomic and Epigenomic alterations after prenatal exposure to Cancer treatment In Pregnancy (GE-CIP): a multicentric observational study |
| title_fullStr | Evaluating offspring Genomic and Epigenomic alterations after prenatal exposure to Cancer treatment In Pregnancy (GE-CIP): a multicentric observational study |
| title_full_unstemmed | Evaluating offspring Genomic and Epigenomic alterations after prenatal exposure to Cancer treatment In Pregnancy (GE-CIP): a multicentric observational study |
| title_short | Evaluating offspring Genomic and Epigenomic alterations after prenatal exposure to Cancer treatment In Pregnancy (GE-CIP): a multicentric observational study |
| title_sort | evaluating offspring genomic and epigenomic alterations after prenatal exposure to cancer treatment in pregnancy ge cip a multicentric observational study |
| url | https://bmjopen.bmj.com/content/14/3/e081833.full |
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