Nucleosome footprinting in plasma cell-free DNA for the pre-surgical diagnosis of ovarian cancer
Abstract Fragmentation patterns of plasma cell-free DNA (cfDNA) are known to reflect nucleosome positions of cell types contributing to cfDNA. Based on cfDNA fragmentation patterns, the deviation in nucleosome footprints was quantified between diagnosed ovarian cancer patients and healthy individual...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-04-01
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| Series: | npj Genomic Medicine |
| Online Access: | https://doi.org/10.1038/s41525-022-00300-5 |
| _version_ | 1811338809874317312 |
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| author | Adriaan Vanderstichele Pieter Busschaert Chiara Landolfo Siel Olbrecht An Coosemans Wouter Froyman Liselore Loverix Nicole Concin Elena Ioana Braicu Pauline Wimberger Els Van Nieuwenhuysen Sileny N. Han Toon Van Gorp Tom Venken Ruben Heremans Patrick Neven Tom Bourne Ben Van Calster Dirk Timmerman Diether Lambrechts Ignace Vergote |
| author_facet | Adriaan Vanderstichele Pieter Busschaert Chiara Landolfo Siel Olbrecht An Coosemans Wouter Froyman Liselore Loverix Nicole Concin Elena Ioana Braicu Pauline Wimberger Els Van Nieuwenhuysen Sileny N. Han Toon Van Gorp Tom Venken Ruben Heremans Patrick Neven Tom Bourne Ben Van Calster Dirk Timmerman Diether Lambrechts Ignace Vergote |
| author_sort | Adriaan Vanderstichele |
| collection | DOAJ |
| description | Abstract Fragmentation patterns of plasma cell-free DNA (cfDNA) are known to reflect nucleosome positions of cell types contributing to cfDNA. Based on cfDNA fragmentation patterns, the deviation in nucleosome footprints was quantified between diagnosed ovarian cancer patients and healthy individuals. Multinomial modeling was subsequently applied to capture these deviations in a per sample nucleosome footprint score. Validation was performed in 271 cfDNAs pre-surgically collected from women with an adnexal mass. We confirmed that nucleosome scores were elevated in invasive carcinoma patients, but not in patients with benign or borderline disease. Combining nucleosome scores with chromosomal instability scores assessed in the same cfDNA improved prediction of malignancy. Nucleosome scores were, however, more reliable to predict non-high-grade serous ovarian tumors, which are characterized by low chromosomal instability. These data highlight that compared to chromosomal instability, nucleosome footprinting provides a complementary and more generic read-out for pre-surgical diagnosis of invasive disease in women with adnexal masses. |
| first_indexed | 2024-04-13T18:16:01Z |
| format | Article |
| id | doaj.art-6571537f895e4d2b8a539a4af5fd1176 |
| institution | Directory Open Access Journal |
| issn | 2056-7944 |
| language | English |
| last_indexed | 2024-04-13T18:16:01Z |
| publishDate | 2022-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Genomic Medicine |
| spelling | doaj.art-6571537f895e4d2b8a539a4af5fd11762022-12-22T02:35:40ZengNature Portfolionpj Genomic Medicine2056-79442022-04-01711910.1038/s41525-022-00300-5Nucleosome footprinting in plasma cell-free DNA for the pre-surgical diagnosis of ovarian cancerAdriaan Vanderstichele0Pieter Busschaert1Chiara Landolfo2Siel Olbrecht3An Coosemans4Wouter Froyman5Liselore Loverix6Nicole Concin7Elena Ioana Braicu8Pauline Wimberger9Els Van Nieuwenhuysen10Sileny N. Han11Toon Van Gorp12Tom Venken13Ruben Heremans14Patrick Neven15Tom Bourne16Ben Van Calster17Dirk Timmerman18Diether Lambrechts19Ignace Vergote20Department of Obstetrics and Gynaecology, University Hospitals Leuven, Leuven Cancer InstituteDepartment of Obstetrics and Gynaecology, University Hospitals Leuven, Leuven Cancer InstituteDepartment of Development and Regeneration, KU LeuvenDepartment of Obstetrics and Gynaecology, University Hospitals Leuven, Leuven Cancer InstituteDepartment of Obstetrics and Gynaecology, University Hospitals Leuven, Leuven Cancer InstituteDepartment of Obstetrics and Gynaecology, University Hospitals Leuven, Leuven Cancer InstituteDepartment of Obstetrics and Gynaecology, University Hospitals Leuven, Leuven Cancer InstituteDepartment of Obstetrics and Gynaecology, University Hospitals Leuven, Leuven Cancer InstituteDepartment of Gynecology, Campus Virchow, Charité, Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of HealthNational Center for Tumor Diseases (NCT)Department of Obstetrics and Gynaecology, University Hospitals Leuven, Leuven Cancer InstituteDepartment of Obstetrics and Gynaecology, University Hospitals Leuven, Leuven Cancer InstituteDepartment of Obstetrics and Gynaecology, University Hospitals Leuven, Leuven Cancer InstituteVIB Center for Cancer BiologyDepartment of Obstetrics and Gynaecology, University Hospitals Leuven, Leuven Cancer InstituteDepartment of Obstetrics and Gynaecology, University Hospitals Leuven, Leuven Cancer InstituteDepartment of Development and Regeneration, KU LeuvenDepartment of Development and Regeneration, KU LeuvenDepartment of Obstetrics and Gynaecology, University Hospitals Leuven, Leuven Cancer InstituteVIB Center for Cancer BiologyDepartment of Obstetrics and Gynaecology, University Hospitals Leuven, Leuven Cancer InstituteAbstract Fragmentation patterns of plasma cell-free DNA (cfDNA) are known to reflect nucleosome positions of cell types contributing to cfDNA. Based on cfDNA fragmentation patterns, the deviation in nucleosome footprints was quantified between diagnosed ovarian cancer patients and healthy individuals. Multinomial modeling was subsequently applied to capture these deviations in a per sample nucleosome footprint score. Validation was performed in 271 cfDNAs pre-surgically collected from women with an adnexal mass. We confirmed that nucleosome scores were elevated in invasive carcinoma patients, but not in patients with benign or borderline disease. Combining nucleosome scores with chromosomal instability scores assessed in the same cfDNA improved prediction of malignancy. Nucleosome scores were, however, more reliable to predict non-high-grade serous ovarian tumors, which are characterized by low chromosomal instability. These data highlight that compared to chromosomal instability, nucleosome footprinting provides a complementary and more generic read-out for pre-surgical diagnosis of invasive disease in women with adnexal masses.https://doi.org/10.1038/s41525-022-00300-5 |
| spellingShingle | Adriaan Vanderstichele Pieter Busschaert Chiara Landolfo Siel Olbrecht An Coosemans Wouter Froyman Liselore Loverix Nicole Concin Elena Ioana Braicu Pauline Wimberger Els Van Nieuwenhuysen Sileny N. Han Toon Van Gorp Tom Venken Ruben Heremans Patrick Neven Tom Bourne Ben Van Calster Dirk Timmerman Diether Lambrechts Ignace Vergote Nucleosome footprinting in plasma cell-free DNA for the pre-surgical diagnosis of ovarian cancer npj Genomic Medicine |
| title | Nucleosome footprinting in plasma cell-free DNA for the pre-surgical diagnosis of ovarian cancer |
| title_full | Nucleosome footprinting in plasma cell-free DNA for the pre-surgical diagnosis of ovarian cancer |
| title_fullStr | Nucleosome footprinting in plasma cell-free DNA for the pre-surgical diagnosis of ovarian cancer |
| title_full_unstemmed | Nucleosome footprinting in plasma cell-free DNA for the pre-surgical diagnosis of ovarian cancer |
| title_short | Nucleosome footprinting in plasma cell-free DNA for the pre-surgical diagnosis of ovarian cancer |
| title_sort | nucleosome footprinting in plasma cell free dna for the pre surgical diagnosis of ovarian cancer |
| url | https://doi.org/10.1038/s41525-022-00300-5 |
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