Prenatal diagnosis of supernumerary ring chromosome 1: case report and review of the literature.

A supernumerary ring chromosome was found on amniocentesis performed for advanced maternal age. A review of the literature found 34 reports of supernumerary ring chromosome I which are compared to our case.

Application of molecular cytogenetic techniques in a case study of human cutaneous metastatic melanoma.

Consistent structural chromosome rearrangements have rarely been identified in adult solid tumors. The introduction of advanced molecular cytogenetic techniques has provided new ways of analyzing highly complex karyotypes commonly encountered in these malignancies. This study describes a detailed molecular cytogenetic analysis of a sporadic human cutaneous melanoma biopsy, M92-047, using a combination of G-banding, fluorescence in situ hybridization (FISH), chromosome microdissection, and comparative genomic hybridization (CGH). G-banding revealed that this tumor was composed primarily of closely related near-diploid and near-tetraploid cell subpopulations containing several clonal numerical and structural chromosome alterations. Fluorescence in situ hybridization using whole chromosome painting probes and chromosome arm painting probes, was employed to verify the rearranged chromosomes; dic(1;4), der(8)t(1;8), and der(15)t(6;15), whereas marker chromosomes dic(8;1;16), der(12)t(9;12), and der(17)t(13;17) were discerned by chromosome microdissection and subsequent reverse in situ hybridization (rev ish) analysis. Comparative genomic hybridization illustrated DNA copy number changes in good agreement with the karyotypic analysis. Although this line exhibits recurrent alterations representative of melanoma, two unique breakpoints--1p13 and 8p21--were identified in two different rearranged chromosomes, suggesting potentially important regions for further dissection by molecular genetic techniques. This report demonstrates the advantages of combining multiple techniques in order to obtain a detailed description of cytogenetic changes in melanoma.

Molecular cytogenetic study of a hemangiopericytoma in a newborn.

Two balanced reciprocal chromosome translocations, t(8;12)(p21;p13. 1) and t(15;16)(q24;q22), characterized a rare hemangiopericytoma in a newborn. Chromosome painting with a chromosome microdissection-derived whole-chromosome 8 probe confirmed that the t(8;12) was due to a reciprocal translocation. To the best of our knowledge, these chromosome findings are unique to this unusual case of a pediatric hemangiopericytoma.

Precise localization by microdissection/reverse ISH and FISH of the t(15;17)(q24;q21.1) chromosomal breakpoints associated with acute promyelocytic leukemia.

The acute promyelocytic leukemia (APL M3)-associated translocation (15;17) has been described as having breakpoints variably located between 15q22 and 15q26, and 17q11 and 17q25. Most of the recent studies using DNA probes (fluorescence in situ hybridization [FISH]) for analysis have indicated the chromosome 15 breakpoint to be in 15q22. We have utilized a combination of G-banding, FISH, and chromosome microdissection/reverse ISH to precisely map the breakpoint to t(15;17)(q24;q21.1).

Proximal 5p trisomy resulting from a marker chromosome implicates band 5p13 in 5p trisomy syndrome.

We describe an infant with trisomy of (5)(p10p13.1) resulting from a de novo marker chromosome. The marker's origin was identified by chromosome microdissection and reverse in situ hybridization. The clinical findings are compared to those of other partial and complete 5p duplications. This case further defines the critical region of 5p trisomy syndrome to proximal 5p.

A molecular cytogenetic study of chromosome 3 rearrangements in small cell lung cancer: consistent involvement of chromosome band 3q13.2.

To more precisely determine the nature of chromosome 3 rearrangements in small cell lung carcinomas (SCLCs), we have applied molecular cytogenetic technologies to a newly characterized SCLC tumor and five SCLC cell lines. Fluorescent in situ hybridization, chromosome microdissection, and, on the previously uncharacterized tumor, spectral karyotyping was utilized to determine chromosome 3 rearrangements. In all cases, our studies were performed on previously G-banded chromosomes in a sequential manner to facilitate a direct comparison. A consistent breakpoint on the long arm of chromosome 3 at band 3q13.2 was identified in all six tumors. This breakpoint was commonly the result of complex chromosomal rearrangements. Loss of the entire short arm of a chromosome 3 was noted in all six tumor cultures. Two of these cell lines had two sublines, one of which contained a 3q13.2 rearrangement and the other of which contained a chromosome rearrangement that resulted in loss of a chromosome 3 short arm. This consistent rearrangement at chromosome band 3q13.2, as demonstrated by molecular cytogenetic methods, may indicate the location of a gene important in the tumorigenesis of SCLC.

A translocation breakpoint at chromosome band 12q13 associated with B-cell chronic lymphocytic leukemia.

Low-grade B-cell lymphoproliferative disorders are frequently associated with an extra copy of chromosome 12. This well-documented acquired anomaly is one of the most specific numerical chromosome alterations to occur in human hematological malignancies. We have cytogenetically characterized bone marrow and peripheral blood cells from a patient with B-cell chronic lymphocytic leukemia (CLL) having a unique acquired translocation involving chromosomes 6 and 12, t(6;12) (p21.3;q13), which implicates band 12q13 as the site of the gene(s) important in this lymphoproliferative B-cell disorder. Aneuploidy, in the form of trisomy of chromosome 12, is not a requirement for neoplastic transformation in B-cell CLL, but gene rearrangement (present case) or nondisjunctional acquisition of additional copies of defective genes on chromosome 12 at band q13 may be involved in the genesis or progression of this disorder.

Chromosome breakpoint at 17q11.2 and insertion of DNA from three different chromosomes in a glioblastoma with exceptional glial fibrillary acidic protein expression.

A glioblastoma that retained glial fibrillary acidic protein (GFAP) in culture has a break in the long arm of chromosome 17 at band 17q11.2. DNA inserted at this breakpoint came from chromosome bands 3p21, 3q23, 16q11.2, and 22q11.2. These chromosome fragments were inserted in band 17q11.2 proximal to the neurofibromatosis-1 (NF-1) gene and neu (HER2; erbB2) oncogene loci. The glioblastoma also contained a reciprocal translocation between 16p12 and 20p12. These structural abnormalities, previously undescribed in gliomas, were demonstrated by high-resolution chromosome banding, microdissection, and fluorescence in situ hybridization (FISH). Numerical changes typical of glioblastoma were present: gain of chromosome 7 and losses of chromosomes 10, 13, and 22. The complex chromosome origin of DNA inserted in this glioma chromosome is described. The association of two infrequent events in this single glioblastoma line, this complex insertion and retention of GFAP expression, is not likely to be a chance occurrence. It raises the possibility of an association between the two events.

Cytogenetic studies of Hodgkin's disease. Analysis of involved lymph nodes from 12 patients.

Cytogenetic studies were performed on 12 involved lymph nodes from Hodgkin's disease patients utilizing conditioned medium from 12-O-tetradecanoylphorbol-13-acetate-staphylococcus enterotoxin A induced mononuclear cells. The majority of cells analyzed had a normal karyotype. An unusually high rate of nonclonal karyotypic abnormalities was noted in most cultures. Clonal abnormalities involving chromosomes 3 and 21 were noted in two patients. Cytogenetic analysis of cultures stimulated with conditioned medium or specific growth factors may lead to a better understanding of the genetic mechanisms involved in Hodgkin's disease.