A novel t(6;14)(q25-q27;q32) in acute myelocytic leukemia involves the BCL11B gene.

Cytogenetic studies in a patient with acute myelocytic leukemia (AML) revealed as the sole karyotypic alteration a half-cryptic rearrangement, identified with 48-color combined binary ratio-labeled fluorescence in situ hybridization (pq-COBRA-FISH) as a reciprocal t(6;14)(q?;q?). The breakpoints were later assigned on the basis of G-banding to t(6;14)(q25-q26;q32). FISH experiments using genomic probes showed that the breakpoint on 14q32.

Multiple supernumerary ring chromosomes of different origin in a patient: a clinical report and review of the literature.

We describe a patient with multiple congenital abnormalities exhibiting 2-5 supernumerary chromosomes per cells. A variety of FISH techniques were used to demonstrate that the markers are probably rings, lack detectable telomere sequences, and originate from different non-acrocentric chromosomes, namely 6, 7, 10, 12, and 19. Such cases are extremely rare and this is only the 8th published report of an individual presenting three or more supernumerary chromosomes.

LAF4, an AF4-related gene, is fused to MLL in infant acute lymphoblastic leukemia.

Infant acute lymphoblastic leukemia (ALL) with MLL gene rearrangements is characterized by a proB phenotype and a poor clinical outcome. We analyzed an infant proB ALL with t(2;11)(p15;p14) and an MLL rearrangement on Southern blot analysis. Rapid amplification of cDNA ends-polymerase chain reaction (PCR) and reverse transcriptase-PCR identified the LAF4 gene mapped on chromosome region 2q11.

Individuals with abnormal phenotype and normal G-banding karyotype: improvement and limitations in the diagnosis by the use of 24-colour FISH.

The simultaneous identification, by fluorescence in situ hybridisation (FISH), of each chromosome in a distinct colour became feasible a few years ago. The key question in the application of this and many other developments in molecular cytogenetics to clinical situations is whether the results add significant further information that is relevant to the diagnosis. So far, limited data exist regarding how much improvement the technique brings to the diagnosis of phenotypically abnormal individuals in whom no abnormalities have been detected by conventional G-banding analysis.

Nasopharyngeal teratoma and mosaic tetrasomy 1q detected at amniocentesis. A case report and review of the literature.

The occurrence of nasopharyngeal teratomas (NPT) is an infrequent event and prenatal detection of such tumors is even rarer. We present a case report and review of the literature (N = 78 cases), in which we describe the cytogenetic, DNA, and pathological findings of a fetus with a mature NPT which was detected prenatally by ultrasound investigation following complaints of severe polyhydramnios by the mother.

Genomic acute myeloid leukemia-associated inv(16)(p13q22) breakpoints are tightly clustered.

The inv(16) and related t(16;16) are found in 10% of all cases with de novo acute myeloid leukemia. In these rearrangements the core binding factor beta (CBFB) gene on 16q22 is fused to the smooth muscle myosin heavy chain gene (MYH11) on 16p13. To gain insight into the mechanisms causing the inv(16) we have analysed 24 genomic CBFB-MYH11 breakpoints.

Prenatal diagnosis of trisomy 13 on fetal cells obtained from maternal blood after minor enrichment.

In a pilot study to establish fetal nucleated red blood cell (NRBC) detection in maternal blood, trisomy 13 was diagnosed by FISH analysis at 11 weeks' gestation. The NRBCs were detected after a single-step ficoll density gradient enrichment. In blood samples taken both before and after CVS, 52 and 80 NRBCs, respectively, were found to be positive for fetal haemoglobin.

A near false-negative finding of mosaic trisomy 21--a cautionary tale.

We report the finding of a mosaic trisomy 21 restricted to the long-term culture of chorionic villi and to one amniotic fluid culture which, if interpreted according to the standard rules for the authentication of mosaicism, would have resulted in a false-negative result. The definitive diagnosis of mosaic Down syndrome was eventually confirmed by cordocentesis and by post-abortion fibroblast cultures.

Fetal cell detection in maternal blood: a study in 236 samples using erythroblast morphology, DAB and HbF staining, and FISH analysis.

A protocol to detect fetal nucleated red blood cells (NRBCs) was tested in 217 pregnant women and in 19 nonpregnant controls. All the pregnant women were sampled after chorionic villus sampling (CVS); 20 were also sampled pre-CVS. NRBC recognition was based upon morphology by using staining of hemoglobin with 3,3-diaminobenzidin (DAB) or by immunocytochemical staining for fetal hemoglobin (HbF).

Development of a preparation and staining method for fetal erythroblasts in maternal blood: simultaneous immunocytochemical staining and FISH analysis.

In order to detect fetal nucleated red blood cells (NRBCs) in maternal blood, a protocol was developed which aimed at producing a reliable staining method for combined immunocytochemical and FISH analysis. The technique had to be suitable for eventual automated screening of slides. Chorionic villi washings, cord blood, and maternal blood samples were used for this study.

Amniocentesis before 14 completed weeks as an alternative to transabdominal chorionic villus sampling: a controlled trial with infant follow-up.

A (semi-) randomized controlled study with long-term follow-up was conducted to compare the effects of transabdominal chorionic villus sampling and early amniocentesis on fetal mortality and child morbidity. Women requesting early prenatal diagnosis for advanced maternal age were allocated to early amniocentesis or transabdominal chorionic villus sampling either by randomization or, if they declined randomization, by their own choice. Of the 212 women who entered the study, 117 were randomized, 70 chose early amniocentesis and 25 chose transabdominal chorionic villus sampling.

Detection of CBP rearrangements in acute myelogenous leukemia with t(8;16).

The CREB-binding protein (CBP) is a large nuclear protein that regulates many signal transduction pathways and is involved in chromatin-mediated transcription. The translocation t(8;16)(p11;p13.3) consistently disrupts two genes: the CBP gene on chromosome band 16p13.

A second case of hexasomy 8 in myelodysplastic syndrome.

Tetrasomy 8 is a rare form of acquired aneuploidy found exclusively in the myeloid leukemias. Hexasomy 8 is even rarer: only one case has been reported, thus far. We describe here the second case of hexasomy 8 as the sole abnormality in an elderly female patient with myelodysplastic syndrome (MDS).

Pitt-Rogers-Danks syndrome and Wolf-Hirschhorn syndrome are caused by a deletion in the same region on chromosome 4p 16.3.

Recently, a deletion of chromosome 4pter was found in three patients with Pitt-Rogers-Danks syndrome. We investigated two of these patients, by means of DNA and FISH studies, together with two additional patients with Pitt-Rogers-Danks syndrome, to determine the critical region of the deletion in these patients and to compare this with the critical region in Wolf-Hirschhorn syndrome. All four patients showed terminal deletions of chromosome 4p of different sizes.

Mosaicism of the 5q deletion as assessed by interphase FISH is a common phenomenon in MDS and restricted to myeloid cells.

Interstitial deletion of chromosome 5q is a common cytogenetic abnormality observed in MDS. We have used fluorescence in situ hybridization (FISH) to determine accurately the percentage of cytogenetically abnormal peripheral blood cells. YAC and cosmid probes localized to chromosome 5q were hybridized to interphase nuclei from purified polymorphonuclear cells (PMNs) from six MDS patients with chromosome 5 deletions.

Prenatal and postnatal investigation of a case with Miller-Dieker syndrome due to a familial cryptic translocation t(17;20) (p13.3;q13.3) detected by fluorescence in situ hybridization.

We present here a case report of a fetus with a kidney anomaly and dilated occipital horns, detected initially by echoscopy at 29 weeks' amenorrhoea. After 31 weeks of gestation, the proband was born with clinical symptoms of Miller-Dieker syndrome. This was subsequently confirmed by fluorescence in situ hybridization (FISH), but not by conventional cytogenetic analysis.

Familial translocations involving 15q11-q13 can give rise to interstitial deletions causing Prader-Willi or Angelman syndrome.

A de novo interstitial deletion of 15q11-q13 is the major cause of Prader-Willi syndrome (PWS) and Angelman syndrome (AS). Here we describe two unrelated PWS patients with a typical deletion, whose fathers have a balanced translocation involving the PWS/AS region. Microsatellite data suggest that the deletion is the result of an unequal crossover between the derivative chromosome 15 and the normal chromosome 15.

Simple method for detection of MYH11 DNA rearrangements in patients with inv(16)(p13q22) and acute myeloid leukemia.

The pericentric inversion on chromosome 16 [inv(16)(p13q22)] and related t(16;16)(p13;q22) are recurrent aberrations associated with acute myeloid leukemia (AML) M4 Eo. Both abberations result in a fusion of the core binding factor beta (CBFB) and smooth muscle myosin heavy chain gene (MYH11). A selected genomic 6.

A case of isodicentric 7p as sole abnormality in a patient with acute myeloid leukemia.

The detection of isochromosomes in the leukemias and in solid tumors has been well described in the literature, the most common being the i(17q), which is found in the blast crisis of CML and terminal stages of acute myeloid leukemia. Reports of isochromosome 7 have, however, been less well represented, particularly isochromosomes of the short arm of chromosome 7, which represent approximately 1% of all reported isochromosomes in neoplasia. We present here a case report of an elderly female patient with AML-M2 who manifested an idic(7p) in the majority of her bone marrow cells.

Detection of 11q13 rearrangements in hematologic neoplasias by double-color fluorescence in situ hybridization.

Rearrangements within the chromosome 11q13 region are frequent in hematologic malignancies. 50% of 75% of mantle cell lymphomas (MCLs) carry a translocation t(11;14) (q13;q32). Using Southern blot analysis, a BCL1 breakpoint can be detected in approximately 50% of MCLs.

Establishment and characterization of an uveal-melanoma cell line.

A human uveal melanoma cell line (92-1) was established from a primary uveal melanoma, and has now been maintained in culture for over 2 1/2 years. Light microscopy of the cultured cells demonstrated extremely pleiomorphic cells with large prominent nucleoli. Cell proliferation was determined with a non-radioactive propidium-iodide assay and indicated an in vitro doubling time of approximately 58 hr.

RT-PCR diagnosis of patients with acute nonlymphocytic leukemia and inv(16)(p13q22) and identification of new alternative splicing in CBFB-MYH11 transcripts.

As acute nonlymphocytic leukemia (ANLL) with inv(16) (p13q22) or t(16;16)(p13;q22) has been shown to result from the fusion of transcription factor subunit core binding factor (CBFB) to a myosin heavy chain (MYH11), we sought to design methods to detect this rearrangement using reverse transcriptase-polymerase chain reaction (RT-PCR). In all of 27 inv(16)(p13q22) and four t(16;16)(p13;q22) cases tested, a chimeric CBFB-MYH11 transcript coding for an in-frame fusion protein was detected. In a more extensive RT-PCR analysis with different primer pairs, we detected a second new chimeric CBFB-MYH11 transcript in 10 of 11 patients tested.