Detection of a case of chronic myeloid leukaemia with deletions at the t(9;22) translocation breakpoints by a genome-wide non-invasive prenatal test.
OBJECTIVE
Non-invasive prenatal tests (NIPTs) interrogating the complete genome are able to detect not only fetal trisomy 13, 18 or 21 but additionally provide information on other (sub)chromosomal aberrations that can be fetal or maternal in origin. We demonstrate that in a subset of cases, this information is clinically relevant and should be reported to ensure adequate follow-up.


METHODS
Genome-wide NIPT was carried out and followed by a software analysis pipeline optimized to detect subchromosomal aberrations.


RESULTS
The NIPT profile showed deletions on chromosomes 9 and 22: NIPT 9q33.3q34.12(129150001-133750000)x1,22q11.23(23550001-25450000)x1,22q13.1(37850001-39600000)x1. This result was confirmed by single nucleotide polymorphism array on maternal genomic DNA, which also demonstrated that the deletions were somatic in nature. Fluorescence in situ hybridization and quantitative real-time polymerase chain reaction revealed that the deletions were flanking the translocation breakpoint on the derivative chromosome 9 as the result of a t(9;22)(q34;q11.2) translocation with BCR-ABL1 fusion typical for chronic myeloid leukaemia (CML). Multidisciplinary counselling, together with complete blood count, taught that the woman was in an early chronic phase CML. The woman was followed up closely, and treatment could be postponed until after delivery.


CONCLUSIONS
Genome-wide NIPT identified a CML in chronic phase caused by the typical t(9;22)(q34;q11.2) translocation and accompanied by deletions flanking the translocation breakpoints. © 2016 John Wiley & Sons, Ltd.
Center of Medical Genetics, University of Antwerp, Wilrijk, Belgium.
Katrien
K
Janssens
Laboratory of Hematology, Antwerp University Hospital, Edegem, Belgium.
Kathleen
K
Deiteren
Department of Hematology, Antwerp University Hospital, Edegem, Belgium.
Anke
A
Verlinden
Center of Medical Genetics, Antwerp University Hospital, Edegem, Belgium.
Liesbeth
L
Rooms
Center of Medical Genetics, Antwerp University Hospital, Edegem, Belgium.
Sigri
S
Beckers
Center of Medical Genetics, Antwerp University Hospital, Edegem, Belgium.
Philip
P
Holmgren
Laboratory of Hematology, Antwerp University Hospital, Edegem, Belgium.
Katrien
K
Vermeulen
Laboratory of Hematology, Antwerp University Hospital, Edegem, Belgium.
Marie-Berthe
MB
Maes
Center of Medical Genetics, University of Antwerp, Wilrijk, Belgium.|Center of Medical Genetics, Antwerp University Hospital, Edegem, Belgium.
Geert
G
Mortier
Center of Medical Genetics, University of Antwerp, Wilrijk, Belgium.|Center of Medical Genetics, Antwerp University Hospital, Edegem, Belgium.
Bettina
B
Blaumeiser
D000328:Adult; D002872:Chromosome Deletion; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D004247:DNA / Q000097:blood* / Q000235:genetics; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011252:Pregnancy Complications, Neoplastic / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D011261:Pregnancy Trimester, First; D011296:Prenatal Diagnosis; D060888:Real-Time Polymerase Chain Reaction; D014178:Translocation, Genetic
D004247:DNA; D016044:Fusion Proteins, bcr-abl