Preimplantation genetic diagnosis for cancer predisposition syndromes.
OBJECTIVE
Mutations in the APC, NF2 and BRCA1 genes cause adult-onset cancer predisposition syndromes. Prenatal diagnosis (PND) and selective pregnancy termination for adult-onset disorders is emotionally difficult and, in some cases, socially not well accepted. Preimplantation genetic diagnosis (PGD) appears as an attractive alternative to PND, as it ensures the establishment of a pregnancy free of the mutation from the onset, circumventing the potentially difficult decision of termination of pregnancy.


METHODS
Development of single-cell PCRs using Epstein-Barr virus transformed lymphoblasts as single-cell model, followed by clinical application in PGD.


RESULTS
A total of five duplex-PCRs were developed, three for adenomatous polyposis of the colon (APC), one for neurofibromatosis type 2 (NF2) and one for inherited breast and ovarian cancer caused by BRCA1 mutations. Eleven clinical cycles were performed, resulting in the birth of an unaffected girl. For one of the couples undergoing PGD for NF2, a spontaneous pregnancy ensued after five unsuccessful PGD cycles. The couple underwent chorionic villus sampling (CVS) and the application of the same protocol as used during PGD showed an unaffected fetus.


CONCLUSIONS
In this work, we present the development and clinical application of PGD for three cancer predisposition syndromes.
Spits
C
C
Research Centre Genetics and Reproduction, Academisch Ziekenhuis, Vrije Universiteit Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium.
De Rycke
M
M
Van Ranst
N
N
Verpoest
W
W
Lissens
W
W
Van Steirteghem
A
A
Liebaers
I
I
Sermon
K
K
D000328:Adult; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics; D003110:Colonic Neoplasms / Q000175:diagnosis / Q000235:genetics; D017931:DNA Primers; D005260:Female; D017491:Genes, APC; D019398:Genes, BRCA1; D016515:Genes, Neurofibromatosis 2; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D016518:Neurofibromatosis 2 / Q000175:diagnosis / Q000235:genetics; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000379:methods*; D011237:Predictive Value of Tests; D011247:Pregnancy; D019836:Preimplantation Diagnosis; D013577:Syndrome
D017931:DNA Primers