Using population-based data to predict the impact of introducing noninvasive prenatal diagnosis for Down syndrome.

PURPOSE: To compare the number and types of chromosome abnormalities prenatally diagnosed and the number of invasive procedures between current prenatal testing pathways and a pathway where noninvasive prenatal diagnosis for Down syndrome replaces Down syndrome screening tests. METHODS: Numbers and types of chromosome abnormalities for each referral category were extracted from prenatal diagnostic testing reports routinely collected in Victoria, Australia, in 2006 and 2007. These data were then applied to the proposed implementation strategy. RESULTS: If noninvasive prenatal diagnosis for Down syndrome had replaced Down syndrome screening tests in 2006 and 2007, in Victoria, there would have been 25 (7%) additional Down syndrome diagnosed, 6896 (84%) fewer invasive procedures, and 231 (56%) non-Down syndrome chromosome abnormalities no longer detected. These include trisomy 13, trisomy 18, sex chromosome abnormalities, balanced and unbalanced rearrangements, polyploidy, and mosaic results. CONCLUSIONS: The potential loss of information about chromosome abnormalities other than Down syndrome with noninvasive prenatal diagnosis compared with full karyotyping with traditional prenatal diagnosis should be considered when planning for the implementation of new technologies.

Dysembryoplastic neuroepithelial tumor (DNT)-like oligodendrogliomas or Dnts evolving into oligodendrogliomas: two illustrative cases.

A review of dysembryoplastic neuroepithelial tumors (DNTs) in 14 patients over a 12-year period revealed four patients re-operated because of changes on magnetic resonance imaging (MRI) suggesting tumor recurrence or progression. In three of these, the histological features were identical to the initial DNT. In the fourth patient, persistent DNT was surrounded by WHO grade 2 oligoastrocytoma. In one of the other 10 patients, WHO grade 2 oligodendroglioma was present in white matter deep to and completely separate from a cortically based DNT. Fluorescence in situ hybridization showed codeletion of 1p and 19q in both the DNT and oligodendroglioma and oligoastrocytoma components. Deletions were not identified in any other tumor. Our findings corroborate other studies that 1p and 19q deletions are uncommon in DNT. These two unusual tumors also raise the possibility that rare DNTs may evolve into oligodendroglioma or oligoastrocytoma. DNTs with this altered biology can be identified by 1p and 19q deletion analysis.

Quantitation of chromosome 1p and 19q deletions in glial tumours by interphase FISH on formalin-fixed paraffin-embedded tissue.

Deletions on chromosomes 1p and 19q identify oligodendroglial tumours that are likely to have a complete response to some chemotherapy regimens and are associated with prolonged patient survival. Detection of these chromosomal alterations is becoming increasingly important in the evaluation of glial tumours. Interphase fluorescence in situ hybridisation (FISH) is one of a number of techniques for detecting deletions, and is an efficient method for screening large numbers of tumours. We used FISH to detect 1p and 19q deletions in formalin-fixed paraffin sections of 11 oligodendrogliomas, 11 oligoastrocytomas, two astrocytomas and four glioblastomas multiforme. 1p and 19q deletion and non-deletion ratios were tabulated in 200 nuclei in each tumour. We found considerable variation between tumours in the fraction of cells with deletions. This variation has not been reported previously and its clinical significance will be clarified with patient follow-up. There was little variation between regions within the same tumour.

Isochromosome 5p mosaicism at prenatal diagnosis: observations and outcomes in six cases at chorionic villus sampling and one at amniocentesis.

We present six cases of 47,+i(5p)/46 mosaicism diagnosed at chorionic villus sampling (CVS), this being the first prospective series to be reported. The clinical indication in each was advanced maternal age. Further prenatal studies in four (amniocentesis, plus fetal blood sampling in one) did not show the isochromosome. In one case, subsequent amniocentesis showed 1/48 in situ colonies with the isochromosome, but fetal blood was karyotypically normal. These five pregnancies resulted in phenotypically normal livebirths; further normal follow-up reports (from age 4 months through 4 years) are noted in four of these. Analysis of placental tissue in one case confirmed the presence of the i(5p) mosaicism. In the remaining case, in which 100% of CVS cultured cells had the i(5p), the pregnancy was terminated. Fetal skin fibroblasts did not show the i(5p). Thus, in none of these six cases was true fetal mosaicism detected, nor an abnormal phenotype noted. We suggest that a 47,+i(5p)/46 karyotype, detected at CVS, may frequently reflect confined placental mosaicism. In addition, we report a case of the primary diagnosis of 47,+i(5p)/46 mosaicism at amniocentesis. The infant appeared normal at birth, but a brain malformation was subsequently identified.