Comprehensive genome-wide analysis of routine non-invasive test data allows cancer prediction: A single-center retrospective analysis of over 85,000 pregnancies

Liesbeth Lenaerts, PhD; Nathalie Brison, PhD; Charlotte Maggen, MD; Leen Vancoillie, PhD; Huiwen Che, MsC; Peter Vandenberghe, MD, PhD; Daan Dierickx, MD, PhD; Lucienne Michaux, MD, Phd; Barbara Dewaele, PhD; Patrick Neven, MD, PhD; Giuseppe Floris, MD, PhD; Thomas Tousseyn, MD, PhD; Lore Lannoo, MD; Tatjana Jatsenko, PhD; Isabelle Vanden Bempt, PhD; Kristel Van Calsteren, MD, PhD; Vincent Vandecaveye, MD, PhD; Luc Dehaspe, PhD; Koenraad Devriendt, MD, PhD; Eric Legius, MD, PhD; Kris Van Den Bogaert, PhD; Joris Robert Vermeesch, PhD; Frédéric Amant, MD, PhD

EClinicalMedicine (May 2021)

Comprehensive genome-wide analysis of routine non-invasive test data allows cancer prediction: A single-center retrospective analysis of over 85,000 pregnancies

Liesbeth Lenaerts, PhD,
Nathalie Brison, PhD,
Charlotte Maggen, MD,
Leen Vancoillie, PhD,
Huiwen Che, MsC,
Peter Vandenberghe, MD, PhD,
Daan Dierickx, MD, PhD,
Lucienne Michaux, MD, Phd,
Barbara Dewaele, PhD,
Patrick Neven, MD, PhD,
Giuseppe Floris, MD, PhD,
Thomas Tousseyn, MD, PhD,
Lore Lannoo, MD,
Tatjana Jatsenko, PhD,
Isabelle Vanden Bempt, PhD,
Kristel Van Calsteren, MD, PhD,
Vincent Vandecaveye, MD, PhD,
Luc Dehaspe, PhD,
Koenraad Devriendt, MD, PhD,
Eric Legius, MD, PhD,
Kris Van Den Bogaert, PhD,
Joris Robert Vermeesch, PhD,
Frédéric Amant, MD, PhD

Affiliations

Liesbeth Lenaerts, PhD: Department of Oncology, KU Leuven, Herestraat 49, Leuven, Belgium
Nathalie Brison, PhD: Center for Human Genetics, University Hospitals Leuven, Herestraat 49, Leuven, Belgium
Charlotte Maggen, MD: Department of Oncology, KU Leuven, Herestraat 49, Leuven, Belgium
Leen Vancoillie, PhD: Center for Human Genetics, University Hospitals Leuven, Herestraat 49, Leuven, Belgium
Huiwen Che, MsC: Department of Human Genetics, KU Leuven, Herestraat 49, Leuven, Belgium
Peter Vandenberghe, MD, PhD: Department of Human Genetics, KU Leuven, Herestraat 49, Leuven, Belgium; Hematology, University Hospitals Leuven, Herestraat 49, Leuven, Belgium
Daan Dierickx, MD, PhD: Department of Oncology, KU Leuven, Herestraat 49, Leuven, Belgium; Hematology, University Hospitals Leuven, Herestraat 49, Leuven, Belgium
Lucienne Michaux, MD, Phd: Center for Human Genetics, University Hospitals Leuven, Herestraat 49, Leuven, Belgium; Department of Human Genetics, KU Leuven, Herestraat 49, Leuven, Belgium
Barbara Dewaele, PhD: Center for Human Genetics, University Hospitals Leuven, Herestraat 49, Leuven, Belgium
Patrick Neven, MD, PhD: Department of Oncology, KU Leuven, Herestraat 49, Leuven, Belgium; Gynaecology and Obstetrics, University Hospitals Leuven, Herestraat 49, Leuven, Belgium
Giuseppe Floris, MD, PhD: Pathology, University Hospitals Leuven, Herestraat 49, Leuven, Belgium; Department of Imaging & Pathology, KU Leuven, Herestraat 49, Leuven, Belgium
Thomas Tousseyn, MD, PhD: Pathology, University Hospitals Leuven, Herestraat 49, Leuven, Belgium; Department of Imaging & Pathology, KU Leuven, Herestraat 49, Leuven, Belgium
Lore Lannoo, MD: Gynaecology and Obstetrics, University Hospitals Leuven, Herestraat 49, Leuven, Belgium; Department of Department of Development and Regeneration, KU Leuven, Herestraat 49, Leuven, Belgium
Tatjana Jatsenko, PhD: Department of Human Genetics, KU Leuven, Herestraat 49, Leuven, Belgium
Isabelle Vanden Bempt, PhD: Center for Human Genetics, University Hospitals Leuven, Herestraat 49, Leuven, Belgium; Department of Human Genetics, KU Leuven, Herestraat 49, Leuven, Belgium
Kristel Van Calsteren, MD, PhD: Gynaecology and Obstetrics, University Hospitals Leuven, Herestraat 49, Leuven, Belgium; Department of Department of Development and Regeneration, KU Leuven, Herestraat 49, Leuven, Belgium
Vincent Vandecaveye, MD, PhD: Radiology, University Hospitals Leuven, Herestraat 49, Leuven, Belgium; Department of Imaging & Pathology, KU Leuven, Herestraat 49, Leuven, Belgium
Luc Dehaspe, PhD: Genomics Core facility, KU Leuven, Herestraat 49, Leuven, Belgium
Koenraad Devriendt, MD, PhD: Center for Human Genetics, University Hospitals Leuven, Herestraat 49, Leuven, Belgium; Department of Human Genetics, KU Leuven, Herestraat 49, Leuven, Belgium
Eric Legius, MD, PhD: Center for Human Genetics, University Hospitals Leuven, Herestraat 49, Leuven, Belgium; Department of Human Genetics, KU Leuven, Herestraat 49, Leuven, Belgium
Kris Van Den Bogaert, PhD: Center for Human Genetics, University Hospitals Leuven, Herestraat 49, Leuven, Belgium; Department of Human Genetics, KU Leuven, Herestraat 49, Leuven, Belgium
Joris Robert Vermeesch, PhD: Center for Human Genetics, University Hospitals Leuven, Herestraat 49, Leuven, Belgium; Department of Human Genetics, KU Leuven, Herestraat 49, Leuven, Belgium; Genomics Core facility, KU Leuven, Herestraat 49, Leuven, Belgium; Corresponding authors.
Frédéric Amant, MD, PhD: Department of Oncology, KU Leuven, Herestraat 49, Leuven, Belgium; Gynaecology and Obstetrics, University Hospitals Leuven, Herestraat 49, Leuven, Belgium; Academic Medical Centers Amsterdam-University of Amsterdam and The Netherlands Cancer Institute-Antoni van Leeuwenhoek, Amsterdam, Netherlands; Corresponding authors.

Journal volume & issue: Vol. 35
p. 100856

Abstract

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Background: Implausible false positive results in non-invasive prenatal testing (NIPT) have been occasionally associated with the detection of occult maternal malignancies. Hence, there is a need for approaches allowing accurate prediction of whether the NIPT result is pointing to an underlying malignancy, as well as for organized programs ensuring efficient downstream clinical management of these cases. Methods: Using a data set of 88,294 NIPT performed at University Hospital Leuven (Belgium) between November 2013 and March 2020, we retrospectively evaluated the positive predictive value (PPV) of our NIPT approach for cancer detection. In this approach, whole-genome cell-free DNA (cfDNA) data from NIPT were scrutinized for the presence of (sub)chromosomal copy number alterations (CNAs) predictive for a malignancy, using an unbiased NIPT analysis pipeline coined GIPSeq. For suspected cases, the presence of a maternal cancer was evaluated via subsequent multidisciplinary clinical follow-up examinations. The cancer-specificity of the identified CNAs in cfDNA was assessed through genetic analyses of a tumor biopsy. Findings: Fifteen women without a cancer history were identified with a GIPSeq result suggestive of a malignant process. Their cfDNA profiles showed either genome-wide aberrations or a single trisomy 8. Upon clinical examinations, a solid or hematological cancer was identified in 4 and 7 cases, respectively. Three women were identified as having a clonal mosaicism. For one case no underlying condition was found. These numbers add to a PPV of 73%. Based on this experience, we presented a multidisciplinary care path for efficient clinical management of these cases. Interpretation: The presented approach for analysing NIPT results has a high PPV, yet unknown sensitivity, for detecting asymptomatic malignancies upon routine NIPT. Given the complexity of diagnosing a pregnant woman with cancer, clinical follow-up should occur in a well-designed multidisciplinary setting, such as via the care model that we presented here. Funding: This work was supported by Research Foundation Flanders and KU Leuven funding.

Published in EClinicalMedicine

ISSN: 2589-5370 (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Medicine: Medicine (General)
Website: https://www.thelancet.com/journals/eclinm/home

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