TY - JOUR
T1 - Comprehensive genome-wide analysis of routine non-invasive test data allows cancer prediction: A single-center retrospective analysis of over 85,000 pregnancies
AU - Lenaerts, Liesbeth
AU - Brison, Nathalie
AU - Maggen, Charlotte
AU - Vancoillie, Leen
AU - Che, Huiwen
AU - Vandenberghe, Peter
AU - Dierickx, Daan
AU - Michaux, Lucienne
AU - Dewaele, Barbara
AU - Neven, Patrick
AU - Floris, Giuseppe
AU - Tousseyn, Thomas
AU - Lannoo, Lore
AU - Jatsenko, Tatjana
AU - Bempt, Isabelle Vanden
AU - van Calsteren, Kristel
AU - Vandecaveye, Vincent
AU - Dehaspe, Luc
AU - Devriendt, Koenraad
AU - Legius, Eric
AU - Bogaert, Kris Van Den
AU - Vermeesch, Joris Robert
AU - Amant, Frédéric
N1 - Funding Information: This work was supported by FWO (G080217N to FA and JRV) and KU Leuven funding (no. C1/018 to JRV). Publisher Copyright: © 2021 The Author(s)
PY - 2021/5/1
Y1 - 2021/5/1
N2 - 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.
AB - 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.
KW - Cancer detection
KW - Clinical follow-up
KW - Non-invasive prenatal testing
UR - http://www.scopus.com/inward/record.url?scp=85105931479&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.eclinm.2021.100856
DO - https://doi.org/10.1016/j.eclinm.2021.100856
M3 - Article
C2 - 34036251
SN - 2589-5370
VL - 35
JO - EClinicalMedicine
JF - EClinicalMedicine
M1 - 100856
ER -