Molecular cytogenetic studies of pediatric ependymomas.

Cytogenetic and molecular studies of ependymomas have previously demonstrated deletions of chromosomes 17 and 22 as frequent abnormalities, implicating inactivation of tumor suppressor genes in the pathogenesis of these tumors. In the present study, we analyzed 22 childhood ependymomas by standard cytogenetic analysis, fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR)-based microsatellite analysis of chromosomes 17 and 22. Microsatellite analysis of chromosome 6 was performed to identify submicroscopic deletions implicated by the cytogenetic studies.

Isochromosome 17q demonstrated by interphase fluorescence in situ hybridization in primitive neuroectodermal tumors of the central nervous system.

We previously reported an i(17q) as a non-random finding in childhood primitive neuroectodermal tumors (PNETs) of the central nervous system. In the present study, we describe a two-color interphase fluorescence in situ hybridization (FISH) assay for detection of chromosome 17 abnormalities in tumors. Thirty-four PNETs were analyzed by FISH with a series of chromosome 17-specific probes which map to 17p13.

Abnormalities of chromosome 22 in pediatric meningiomas.

Cytogenetic studies of eight meningiomas in young children or adolescents were performed. Two tumors exhibited normal karyotypes. Two tumors from patients with bilateral acoustic neurofibromatosis demonstrated monosomy 22 as the only abnormality.

Enhanced MYCN expression and isochromosome 17q in pineoblastoma cell lines.

We have established two cell lines, PER-452 and PER-453, from an 8-month-old girl with an extensive pineoblastoma. Characterization of these lines revealed that the proto-oncogenes MYC and MYCN were not amplified, but both cell lines showed MYCN expression comparable to a cell line with 200-fold MYCN amplification. Both cell lines contained an i(17q).

46,XX,15p+ documented as dup (17p) by fluorescence in situ hybridization.

We report on a patient with a complex heart defect, short webbed neck, multiple other minor features, and a 46,XX,15p+ de novo karyotype. The enlarged short arm of the chromosome 15 was Distamycin-DAPI and C-band negative. Fluorescence in situ hybridization (FISH) using an alpha satellite probe from chromosome 15 demonstrated hybridization only to the normal 15.

Cytogenetics of melanocytic tumors.

Chromosome studies of human melanocytic tumors have demonstrated non-random karyotypic abnormalities of chromosomes 1, 6, 7, 9, and 10. These visible genetic alterations may provide clues to the location of oncogenes and suppressor genes involved in the development of lesions from benign nervus to metastatic melanoma, and to the mechanisms by which the function of these genes is altered. To date, however, none of the specific growth regulatory genes important in this neoplastic progression has been identified, with the possible exception of the erbB oncogene in the later stages.

Molecular analysis of a partial deletion of 22q in a central nervous system rhabdoid tumor.

We previously reported the non-random occurrence of monosomy 22 in rhabdoid or atypical teratoid tumors of the brain in three young children. We now present cytogenetic and molecular studies of an additional rhabdoid tumor with the karyotype 46,XX,-9,-22,+i(1q),+der(22)t(9;22)(p13;q11)/45,XX,-9,-10,- 22,+i(1q),+der(22)t(9;22)(p13;q11). These studies further demonstrate the involvement of chromosome 22, and they begin to define the critical region containing a gene or genes involved in the development or progression of rhabdoid tumors of the brain.

Malignant fibrous histiocytoma of the brain in a six-year-old girl.

We have prepared karyotypes from a malignant fibrous histiocytoma (MFH) of the brain of a 6-year-old girl. Sporadic cases of MFH in the central nervous system have been reported. However, to our knowledge, this is the first central nervous system tumor to be subjected to cytogenetic analysis.

Chromosomal translocation t(1;13)(p36;q14) in a case of rhabdomyosarcoma.

Cytogenetic studies of a rhabdomyosarcoma of mixed embryonal and alveolar histology in an 11-month-old male revealed a single structural abnormality, t(1;13)(p36;q14). This abnormality may define a subset of patients with a variant of the t(2;13)(q35;q14) translocation frequently seen in alveolar rhabdomyosarcoma.

In vitro properties of human melanoma cells metastatic in nude mice.

We have developed a human melanoma metastasis model in nude mice. In this model, a human variant cell line (451-LU) was obtained that spontaneously metastasized in nude mice. This variant cell line was selected from the lung of a nude mouse after several in vivo passages of human melanoma WM164 cells previously isolated from a melanoma metastasis of a patient.

Possible involvement of the chromosome region 10q24----q26 in early stages of melanocytic neoplasia.

A recent report described a translocation involving 10q24 in a compound nevus. We have examined our series of melanocytic tumors ranging from common nevi to metastatic melanomas with the following results. In 24 nevi (congenital or common acquired), no karyotypically abnormal clones were found.

Structural alteration in the MYB protooncogene and deletion within the gene encoding alpha-type protein kinase C in human melanoma cell lines.

A correlative study was done to determine possible relationships between nonrandom aberrations in chromosomes 1, 6, and 7 occurring in human cutaneous malignant melanoma and the structure of oncogenes as well as specific genes encoding growth factors and growth factor receptors. Thirty cell lines derived from primary or metastatic melanomas of 28 patients were analyzed by Southern blotting with nick-translated probes for 28 different genes, some of which map near frequent chromosomal breakpoints observed in melanoma. An alteration in the MYB protooncogene was observed in a cell line derived from a primary melanoma in the vertical growth phase, which correlated with a 6q22 chromosomal abnormality.

A t(1;19) chromosome translocation in three cases of human malignant melanoma.

Abnormalities of chromosome 1, including trisomy for all or a portion of the long arm, have been frequently reported in many cancers. Anomalies of chromosome 19 are far less common, although a t(1;19)(q23;p13) translocation has been reported in association with pre-B-cell leukemia. We have observed a t(1;19)(q12;p13) translocation in three cases of advanced melanoma, with the translocation chromosome representing an extra dose of 1q in each instance.

N-myc amplification in multiple homogeneously staining regions in two human neuroblastomas.

Molecular characterization of two human neuroblastoma cell lines has revealed that both contain multiple homogeneously staining regions (HSRs), each representing a chromosome site of N-myc amplification. The newly established cell line CHP-382/JK had two cytogenetically distinct populations with several identical chromosomal abnormalities, indicating a common progenitor cell. Each population had one HSR, one on chromosome 5 at q31-34 and the other on chromosome 2 at q31-32.

Expression of the receptor for epidermal growth factor correlates with increased dosage of chromosome 7 in malignant melanoma.

Epidermal growth factor (EGF) receptor is expressed selectively by human melanoma cells which show the presence of an extra copy of chromosome 7. None of the cells of benign pigmented lesions (nevi) or radial growth phase (nonmetastatic) primary melanoma expressed EGF receptor and none of these cells showed an extra copy of chromosome 7. The results indicate that a single extra dose of a gene (for EGF receptor) may provide a selective advantage to cells in the late stages of tumorigenesis.