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

EClinicalMedicine

Joris Robert Vermeesch, PhD¹  Giuseppe Floris, MD, PhD²  Koenraad Devriendt, MD, PhD³  Kristel Van Calsteren, MD, PhD³  Tatjana Jatsenko, PhD⁴  Barbara Dewaele, PhD⁵  Daan Dierickx, MD, PhD⁵  Vincent Vandecaveye, MD, PhD⁶  Eric Legius, MD, PhD⁶  Leen Vancoillie, PhD⁷  Nathalie Brison, PhD⁷  Thomas Tousseyn, MD, PhD⁷  Patrick Neven, MD, PhD⁷  Peter Vandenberghe, MD, PhD⁸  Huiwen Che, MsC⁸  Frédéric Amant, MD, PhD⁸  Charlotte Maggen, MD⁹  Liesbeth Lenaerts, PhD⁹  Lore Lannoo, MD⁹  Lucienne Michaux, MD, Phd⁹  Kris Van Den Bogaert, PhD^1,10  Luc Dehaspe, PhD^1,11  Isabelle Vanden Bempt, PhD^1,11 

[1] Department of Department of Development and Regeneration, KU Leuven, Herestraat 49, Leuven, Belgium;Department of Human Genetics, KU Leuven, Herestraat 49, Leuven, Belgium;;Department of Imaging &Gynaecology and Obstetrics, University Hospitals Leuven, Herestraat 49, Leuven, Belgium;Hematology, University Hospitals Leuven, Herestraat 49, Leuven, Belgium;Pathology, KU Leuven, Herestraat 49, Leuven, Belgium;Center for Human Genetics, University Hospitals Leuven, Herestraat 49, Leuven, Belgium;Department of Human Genetics, KU Leuven, Herestraat 49, Leuven, Belgium;Department of Oncology, KU Leuven, Herestraat 49, Leuven, Belgium;Gynaecology and Obstetrics, University Hospitals Leuven, Herestraat 49, Leuven, Belgium;Pathology, University Hospitals Leuven, Herestraat 49, Leuven, Belgium;

关键词: Non-invasive prenatal testing;    Cancer detection;    Clinical follow-up;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown