Prenatal detection of mosaicism for a genome wide uniparental disomy cell line in a cohort of patients: Implications and outcomes.

OBJECTIVES: To investigate the prenatal detection rate of mosaicism by SNP microarray analysis, in which an individual has not one, but two, complete genomes (sets of DNA) in their body, a normal biparental line with a Genome Wide Uniparental Disomy (GWUPD) cell line was used. METHODS: This study retrospectively examines the prenatal detection of GWUPD in a cohort of ∼90,000 prenatal specimens and ∼20,000 products of conceptions (POCs) that were studied by SNP microarray. RESULTS: In total, 25 cases of GWUPD were detected; 16 cases were detected prenatally with GWUPD (∼0.018%) and 9 POCs revealed GWUPD (0.045%). The nine POC specimens presented with placental abnormalities. The 12 amniotic fluid specimens were ascertained because of abnormal ultrasound findings. Nine of 12 pregnancies had findings consistent with Beckwith-Wiedemann syndrome or because of abnormal placentas. However, three pregnancies were detected with GWUPD of maternal origin, with less common findings and demonstrated maternal origin. Four other pregnancies showed GWUPD in a chorionic villus sample, but normal findings in amniotic fluid and apparently normal fetal development. CONCLUSIONS: This cohort with GWUPD mosaicism expands our understanding of GWUPD and has implications for prenatal care and counseling. Additional studies are necessary to understand the rarer maternal GWUPD.

B-lymphoblastic leukemia/lymphoma with MYC and BCL2 gene rearrangements shows evidence for clonal evolution and mitotic recombination.

BACKGROUND: B-lymphoblastic leukemia/lymphomas (B-ALL/LBL) are uncommon neoplasms that may be associated with a variety of cytogenetic and molecular changes. The mechanisms by which these changes arise have not been fully described. AIMS/PURPOSE: This report describes an unusual case of B-ALL/LBL with complex clonal evolution that includes BCL2 and MYC gene rearrangements. METHODS: Immunophenotyping was performed by immunohistochemistry and flow cytometry. Traditional G-band karyotyping was accompanied by fluorescence in-situ hybridization (FISH) using break-apart and dual fusion probes. Single nucleotide polymorphisms were assessed using a high-density DNA microarray. RESULTS: The karyotype of the blasts showed reciprocal translocation of chromosomes 4 and 18, reciprocal translocation of chromosomes 8 and 14 with two copies of the oncogenic translocation derivative(14)t(8;14), and no normal chromosome 14. FISH studies showed complex IGH-BCL2 and IGH-MYC fusion signals. CONCLUSIONS: A clonal evolution model involving multiple chromosomal translocations and mitotic recombination is postulated to account for the karyotype, FISH, and microarray results but leaves unresolved the exact order of the evolutionary changes.