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PURPOSE - Sinonasal undifferentiated carcinoma (SNUC) is a rare and aggressive cancer. Despite the use of multimodality treatment, the overall prognosis remains poor. To better understand the biologic features of SNUC and help develop new therapies for the disease, we established SNUC cell lines and characterized their biologic behaviors.
EXPERIMENTAL DESIGN - Cell lines were established from a patient with a T4N0M0 SNUC of the right maxillary sinus who was treated with surgical resection at our center. Tumor colonies were harvested and were sequentially replated onto larger plates. Two populations were developed and labeled MDA8788-6 and MDA8788-7. These cell lines were characterized with molecular, biomarker, functional, and histologic analyses.
RESULTS - Short tandem repeat genotyping revealed that the cell line is isogenic to the parental tumor, and cytogenetic analysis identified 12 chromosomal translocations. The SNUC cell lines do not form colonies in soft agar but are tumorigenic and nonmetastatic in an orthotopic mouse model of sinonasal cancer. Western blot analysis revealed that both MDA8788 cell lines express epithelial markers but do not express mesenchymal markers or the endocrine marker synaptophysin.
CONCLUSIONS - This is the first report of the establishment of stable human-derived SNUC cell lines. The lines were highly tumorigenic and maintain the histologic and molecular features of the original tumor. These cell lines should serve as useful tools for the future study of SNUC biology and the development and testing of novel therapies for this deadly disease.
We report a simple procedure that allows the application of chromosomal in situ suppression hybridization to standard G-banded and Entellan-mounted archival preparations that had been stored for 4-8 y. The procedure includes removing the cover slips in xylene, refixation in buffered formaldehyde-acetone mixture, and washing in 2 x SSC, Tween 20.
We looked for clonal chromosomal abnormalities in myeloid cell lineages in the bone marrow aspirates from six children with acute lymphoblastic leukemia (ALL). The study was carried out using a combination of MAC (morphology, antibody, chromosomes) and in situ hybridization procedures. In patients whose leukemic cells expressed only lymphoid antigens, we found chromosomal aberrations in CD10- and CD20/22-positive lymphoid cells. Mature CD22+ and CD3+ lymphocytes did not have the chromosomal aberrations. In one patient whose leukemic cells also expressed myeloid-associated antigens, the clonal chromosome aberrations were seen not only in the CD10+ and CD19+ blasts, but also in glycophorin A-positive morphologically nonleukemic erythroblasts.
Complementary DNA clones encoding human cytosolic phosphoenolpyruvate carboxykinase (GTP) [GTP: oxaloacetate carboxy-lyase (transphosphorylating), EC 18.104.22.168) (PEPCK)] were isolated from a human kidney cDNA library. The nucleotide sequence of the 2.7 kb insert of one of these clones indicates that human PEPCK is a protein of 622 amino acids whose sequence shows 90% identity with that of the cognate rat enzyme. The human PEPCK gene (PCK1) was isolated by hybridization using a fragment of the hPEPCK cDNA as a probe. PCK1 was mapped to human chromosome 20 using DNA from a panel of reduced human-hamster somatic cell hybrids. This assignment was confirmed using fluorescence in situ chromosomal hybridization which localized PCK1 to chromosome 20, band q13.31. A simple tandem repeat DNA polymorphism in the 3'-untranslated region of the mRNA was characterized and used to localize PCK1 relative to the gene responsible for a form of non-insulin-dependent (Type 2) diabetes mellitus called maturity-onset diabetes of the young (MODY). Linkage studies showed that PCK1 is not tightly linked to MODY in one large pedigree and exclude this diabetes candidate gene as the cause of MODY in this family.
Cultures from metastatic melanomas of 15 patients had detailed melanoma growth stimulatory activity (MGSA) and cytogenetic analysis. The presence of melanoma cells was confirmed by microscopic identification of melanin, tyrosinase activity, and electron microscopy characterization of melanosomes. The MGSA is found in cytoplasmic granules after immunocytochemical stain. Three of the cultures did not produce MGSA and showed no distinctive cytogenetic differences. Breakpoints in derivative chromosomes were concentrated in region 1p1, and among all cultures chromosome 1 was the most frequently rearranged. It also has a low copy number of normal homologs. Chromosomes 18, X, and Y were never derivative, and chromosomes 2 and 4 were rarely so. Thus the cytogenetic data indicate that 4q13-21, the hybridization site for MGSA cDNA, is spared from gross change, although it could be under the influence of another site on chromosome 1 that is lost or rearranged. The ratio of abnormal to normal autosomes (mean per cell) in no culture exceeded 0.5, and for no autosome exceeded 0.8, suggesting a limit to the rearrangement tolerated for cell survival. If the Y is retained, the X:Y ratio varies around a normal figure of 1. The ratio of autosomes to sex chromosomes varies around a normal figure of 22. These data suggest stability of the X chromosome in cells undergoing multiple rearrangements of the autosomes.
Ltk is a new member of the ros/insulin receptor family of tyrosine kinases that is expressed in murine B-lymphocyte precursors and forebrain neurons. We previously reported that lymphoid ltk cDNAs predict a 69 kDa transmembrane glycoprotein, which uses a CUG translational start codon and has a 110 amino acid putative extracellular domain. We now show that the predominant ltk mRNA in brain is alternatively spliced and predicts a protein with a substantially larger extracellular part. The human ltk gene maps to chromosome 15, bands q13-21, a region containing the breakpoint of a recurring chromosomal abnormality in B-cell non-Hodgkin lymphomas.
The gene for human P450(17 alpha) (CYP17) was previously mapped to chromosome 10 through analysis of somatic cell hybrids. Using a modified procedure of fluorescence in situ hybridization, this gene has now been visualized on simultaneously banded chromosomes and localized to a specific subband of chromosome 10 at q24.3. This precise assignment may facilitate the understanding of the molecular basis of 17 alpha-hydroxylase/17,20-lyase deficiency and the evolution of the CYP superfamily of genes.