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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Analysis of chromosome abnormalities by comparative genomic hybridization in malignant peripheral primitive neuroectodermal tumor of the ovary.

OBJECTIVE: Malignant primitive neuroectodermal tumor (PNET) originating from the ovary rather than from the central nervous system is extremely rare. The aim of this study is to demonstrate the chromosomal abnormalities in a case of peripheral primitive neuroectodermal tumor (PPNET) arising from the ovary of a girl. METHODS: The 13-year-old girl underwent exploratory laparotomy because of a huge pelvic tumor in lower abdomen and pelvis. She underwent removal of ovaries, tubes, omentum, peritoneal nodules, and portion of urinary bladder. Tumor specimens were sent for pathology, short-term tissue culture, and for storage in deep freezer for laboratory studies. Immunohistochemical stainings of the tumor with antibodies against O-13 (MIC/CD99), NSE, GFAP, S-100, cytokeratin AE1/ AE3, desmin, NF, and AFP were performed. Short-term cell culture of fresh tumor was done for analysis of chromosomal aberrations by the technique of comparative genomic hybridization (CGH). Names of specific genes corresponding to the losses or gains on gene map loci were identified from OMIM (Online Mendelian Inheritance in Man) of the NCBI website,. The overexpressions of N-myc and EGFR as well as underexpressions of Rb and ARHI were detected by RT-PCR analysis. The patient expired 17 months later despite of chemotherapy, repeated surgery, and radiation therapy. RESULT: The histopathology of the specimens revealed malignant neuroectodermal tumor, involving ovaries, tubes, bladder, omentum, and peritoneum. Immunohistochemical stainings of PPNET of the ovary showed positive reaction for O-13 (MIC2/CD99) and NSE, but negative for GFAP, S-100, cytokeratin AE1/ AE3, desmin, NF, and AFP. Analysis of CGH revealed multiple chromosomal abnormalities including losses of chromosomes in 1p, 1q, 4q, 6p, 6q, 7q, 8q, 13q, and 19q; as well as gains of chromosomes in 1q, 2p, 7p, 9q, 18q, and Xq. Losses of 13q14.1-q14.2, 1p31, and 4q34-q35 indicated that Rb gene, ARHI, and FAT were deleted. Gains of 2p24.1, 1q23, and 7p12.3-p12.1 demonstrated that N-myc oncogene, FASL, GITRL, and EGFR were amplified. RT-PCR analysis showed that N-myc and EGFR were overexpressed, while Rb and ARHI were underexpressed. CONCLUSIONS: This report is the first to show multiple chromosomal aberrations in PPENT arising from the ovary. The deletions of Rb, ARHI, and FAT, as well as amplification of N-myc, FASL, GITRL, and EGFR, may be the crucial factors for tumorigenesis and the aggressive biological behavior of PPNET.[1]


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