Der(6)t(1;6)(q21-23;p21.3): a specific cytogenetic abnormality in myelofibrosis with myeloid metaplasia.

Chromosome anomalies are detected in approximately half of patients with myelofibrosis with myeloid metaplasia (MMM) although none of the most prevalent lesions are specific to the disease. In a prospective cytogenetic study of 81 patients with MMM, we encountered three with an unbalanced translocation between chromosomes 1 and 6 with specific breakpoints; der(6)t(1;6)(q21-23;p21.3).

Primer on medical genomics. Part XI: Visualizing human chromosomes.

In the past century, various methods to visualize human chromosomes were discovered. Chromosome analyses provide an overall view of the human genome that cannot be achieved with any other approach. The methods to visualize chromosomes include various techniques to produce bands along chromosomes, specialized procedures for specific disorders, and fluorescent-labeled DNA for targeted loci.

Highly sensitive fluorescence in situ hybridization method to detect double BCR/ABL fusion and monitor response to therapy in chronic myeloid leukemia.

We investigated a new method using fluorescence in situ hybridization and DNA probes that span the common breakpoints of t(9;22)(q34;q11.2) and that detect double BCR/ABL fusion (D-FISH) in bone marrow cells with this translocation, one on the abnormal chromosome 9 and one on the Philadelphia chromosome (Ph chromosome). D-FISH patterns were abnormal in 30 of 30 specimens with classic, simple, complex, and masked Ph chromosomes.

Spectral karyotyping refines cytogenetic diagnostics of constitutional chromosomal abnormalities.

Karyotype analysis by chromosome banding is the standard method for identifying numerical and structural chromosomal aberrations in pre- and postnatal cytogenetics laboratories. However, the chromosomal origins of markers, subtle translocations, or complex chromosomal rearrangements are often difficult to identify with certainty. We have developed a novel karyotyping technique, termed spectral karyotyping (SKY), which is based on the simultaneous hybridization of 24 chromosome-specific painting probes labeled with different fluorochromes or fluorochrome combinations.

Dynamics of chromosome spreading.

Consistency of optimum chromosome spreading during harvest of cytogenetic specimens remains a major concern. We have tested the idea that a precise control of the drying rate (the time with which metaphase cells dry), as fixed cell suspension is placed on a slide or an in situ culture in last fixation, may be the answer. Amniocyte and lymphocyte cultures were allowed to dry at defined combinations of relative humidity (RH) and temperature (T) in a modified Thermotron environmental control unit.

Fluorescent in situ hybridization studies of lymphocytes and neutrophils in chronic granulocytic leukemia.

Using immunomagnetic cell separation and fluorescent in situ hybridization (FISH), we studied nine patients who had chronic granulocytic leukemia (CGL) for the proportion of interphase nuclei with Mbcr/abl fusion in a direct preparation of the bone marrow and also in the mononuclear cell (MNC), neutrophil, and B- and T-cell fractions of the peripheral blood. In five untreated patients, conventional cytogenetics revealed 97% to 100% Philadelphia chromosome (Ph)+ metaphases. In three of these five patients, FISH studies on bone marrow direct preparations and peripheral blood MNCs indicated that an Mbcr/abl fusion occurred in 62% to 69% of the cells.

The application of fluorescent in situ hybridization to detect Mbcr/abl fusion in variant Ph chromosomes in CML and ALL.

We investigated the usefulness of fluorescent in situ hybridization with different-colored major breakpoint cluster region (Mbcr) and Abelson oncogene (abl) probes in clinical practice. In standard Ph chromosomes with a Mbcr breakpoint, these probes produced a fusion of Mbcr and abl signals that was visible in interphase and metaphase cells. The normal range for apparent Mbcr/abl fusion signals in interphase nuclei was established in bone marrow from 25 normal controls.

Method for sequential staining of GTL-banded metaphases with fluorescent-labeled chromosome-specific paint probes.

We describe a method for use of fluorescent-labeled whole chromosome-specific paint probes on GTL-banded metaphases to utilize the combined potential of these techniques for defining chromosome abnormalities. The efficacy of this method was tested on 6 cases involving different chromosome abnormalities and various tissues, including blood, amniotic fluid, skin fibroblasts, and bone marrow.

Cytogenetic guidelines for fragile X studies tested in routine practice.

Several organizations have proposed guidelines for fra(X) studies on peripheral blood lymphocytes. To evaluate these guidelines, we reviewed 1,033 consecutive specimens referred for fra(X) analysis. Each specimen was cultured with medium 199 and RPMI 1640 with 5-fluorodeoxyuridine or excess thymidine.

Cytogenetics of six follicular thyroid adenomas including a case report of an oxyphil variant with t(8;14)(q13;q24.1).

Cytogenetic analyses were performed on six follicular thyroid adenomas. Five had normal karyotypes and one, an oxyphil adenoma, had a t(8;14)(q13;q24.1).

Frequent occurrence of cytogenetic abnormalities in sporadic nonmedullary thyroid carcinoma.

Cytogenetic studies may provide important clues to the molecular pathogenesis of thyroid neoplasia. Thus, the authors attempted cytogenetic studies on 12 thyroid carcinomas: seven papillary, three follicular, and two anaplastic. Successful cytogenetic results were obtained on all 12 tumors; nine (75%) had one or more chromosomally abnormal clones.

Culturing and robotic harvesting of bone marrow, lymph nodes, peripheral blood, fibroblasts, and solid tumors with in situ techniques.

We have modified our in situ method for culturing amniocytes and have successfully used this new procedure to culture cells from bone marrow, lymph nodes, peripheral blood, fibroblasts, and solid tumors. We have been so satisfied with this method that we have used it in our routine practice for the past 2.5 years.

Chromosomally abnormal clones and nonrandom telomeric translocations in cardiac myxomas.

Cardiac myxomas from eight patients were examined cytogenetically in short-term cultures. Cultures could not be established in two of the eight cases. Chromosomally abnormal clones occurred in two of the myxomas; their karyotypes were 45,X,-Y,+7,-18 and 45,X,-Y.

T-lymphocytes with 7;14 translocations: frequency of occurrence, breakpoints, and clinical and biological significance.

Among 11,915 consecutive patients and 37 normal controls who had chromosome analysis at the Mayo Clinic between 1978 and 1984, 83 had a single sporadic metaphase with a 7;14 translocation. In 81 of the translocations, the breakpoints were at 14q11 and either 7q34 (type I) or 7p13 (type II): type I translocations occurred in 42 patients, and type II, in 39. The two other translocations had different breakpoints: one was t(7;14)(q11;q32), and the other was t(7;14)(p13;q32).

Chromosome abnormalities in malignant hematologic disorders.

Certain chromosome abnormalities have been detected in routine cytogenetic studies of patients with hematologic disorders. This article is a cytogenetic and clinical review of 28 structural and 15 numeric chromosome abnormalities. As a group, the structural abnormalities involved 40 different chromosome breakpoints and included 13 types of translocations, 8 deletions, 3 isochromosomes, 3 inversions, and 1 duplication.

The anticentromere antibody: disease specificity and clinical significance.

Serum samples from 539 subjects were screened for the presence of the anticentromere antibody on a human laryngeal carcinoma (HEp-2) cell line (Antibodies, Inc.). The antibody was present in 61 patients (11%), most of whom had features of limited scleroderma or the CREST syndrome (calcinosis cutis, Raynaud's phenomenon, esophageal dysfunction, sclerodactyly, and telangiectasia), either independently or in association with primary biliary cirrhosis.

A possible specific chromosome marker for monocytic leukemia: three more patients with t(9;11)(p22;q24) and another with t(11;17)(q24;q21), each with acute monoblastic leukemia.

An apparently balanced 9;11 reciprocal translocation with break points most likely at 9p22 and 11q24 was found in 3 patients with acute monocytic leukemia [M5 in the French-American-British (FAB) classification schema]. This translocation was not observed in 6 other patients with M5 acute nonlymphocytic leukemia (ANLL) or in chromosome studies on 143 patients with other types of ANLL. This study supports the previously published suggestion that such 9;11 translocations may be associated with some patients with M5 ANLL.

Origin of chi46,XX/46,XY chimerism in a human true hermaphrodite.

Using chromosome heteromorphisms and blood cell types as genetic markers, we demonstrated chimerism in a chi46,XX/46,XY true hermaphrodite. The pattern of inheritance of the chromosome heteromorphisms indicates that this individual was probably conceived by the fertilization, by two different spermatozoa, of an ovum and the second meiotic division polar body derived from the ovum and subsequent fusion of the two zygotes. This conclusion is based on the identification of the same maternal chromosomes 13, 16, and 21 in both the 46,XX and 46,XY cells of the patient.

A tdic(5;15)(p31;p11) chromosome showing variation for constriction in the centromeric regions in a patient with the cri du chat syndrome.

Some dicentric chromosomes show only one primary constriction at metaphase and behave in cell division as if they are monocentric. The few previous reports of tdic (translocation dicentric) chromosomes showing one morphologic indicate that among the cells of an individual the same centromere consistently shows the primary constriction. The present case deals with a tdic(5;15)(p13;p11) chromosome that is an exception to this pattern.

Replication patterns of three isodicentric X chromosomes and an X isochromosome in human lymphocytes.

Chromosomes from four patients with variants of the Turner syndrome were investigated by G- and C-bandind and DNA replication techniques. Their karyotypes were: 1) 46,X,idic(X)(q28), 2) 45,X/46,X,idic(X)(q24), 3) 45,X/46,X,idic(X)(p11), and 4) 46,X,i(Xq). In patients 1, 2, and 3, the abnormal X was isodicentric, with different break-and-fusion points in each case.