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Allelic deletions on the short arm of chromosome 6 (6p) are one of the common, possibly early, genetic changes that occur in the pathogenesis of cervical carcinoma (CC). Previous loss of heterozygosity (LOH) studies in CC identified a number of critical regions of deletions on 6p. However, the precise location of minimally deleted regions and their role in(More)
BACKGROUND Cervical cancer (CC), a leading cause of cancer-related deaths in women worldwide, has been causally linked to genital human papillomavirus (HPV) infection. Although a host of genetic alterations have been identified, molecular basis of CC development is still poorly understood. RESULTS We examined the role of promoter hypermethylation, an(More)
BACKGROUND Male germ cell tumor (GCT) is a highly curable malignancy, which exhibits exquisite sensitivity to cisplatin treatment. The genetic pathway(s) that determine the chemotherapy sensitivity in GCT remain largely unknown. RESULTS We studied epigenetic changes in relation to cisplatin response by examining promoter hypermethylation in a cohort of(More)
The mutant JAK2V617F tyrosine kinase (TK) is present in the majority of patients with BCR-ABL-negative myeloproliferative neoplasms (MPNs). JAK2V617F activates downstream signaling through the signal transducers and activators of transcription (STAT), RAS/mitogen-activated protein kinase (MAPK), and phosphatidylinositol 3 (PI3)/AKT pathways, conferring(More)
BACKGROUND Human male germ cell tumors (GCTs) arise from undifferentiated primordial germ cells (PGCs), a stage in which extensive methylation reprogramming occurs. GCTs exhibit pluripotentiality and are highly sensitive to cisplatin therapy. The molecular basis of germ cell (GC) transformation, differentiation, and exquisite treatment response is poorly(More)
We performed comparative genomic hybridization (CGH) and high-resolution deletion mapping of the long arm of chromosome 2 (2q) in invasive cervical carcinoma (CC). The CGH analyses on 52 CCs identified genetic losses at 2q33-q36, gain of 3q26-q29, and frequent chromosomal amplifications. Characterization of 2q deletions by loss of heterozygosity (LOH) in 60(More)
The PRC2 complex protein EZH2 is a histone methyltransferase that is known to bind and recruit DNMT1 to the DNA to modulate DNA methylation. Here, we determined that the pan-HDAC inhibitor panobinostat (LBH589) treatment depletes DNMT1 and EZH2 protein levels, disrupts the interaction of DNMT1 with EZH2, as well as de-represses JunB in human acute leukemia(More)
The AXL receptor tyrosine kinase and its major ligand, GAS6 have been demonstrated to be overexpressed and activated in many human cancers (such as lung, breast, and pancreatic cancer) and have been correlated with poor prognosis, promotion of increased invasiveness/metastasis, the EMT phenotype and drug resistance. Targeting AXL in different model systems(More)
Heat shock protein (hsp) 90 inhibitors promote proteasomal degradation of pro-growth and pro-survival hsp90 client proteins, including CDK4, c-RAF and AKT, and induce apoptosis of human lymphoma cells. The pan-histone deacetylase inhibitor vorinostat has also been shown to induce growth arrest and apoptosis of lymphoma cells. Here, we determined the effects(More)
PURPOSE To further understand the molecular pathogenesis of pulmonary sarcomatoid carcinoma (PSC) and develop new therapeutic strategies in this treatment-refractory disease. MATERIALS AND METHODS Whole-exome sequencing in a discovery set (n = 10) as well as targeted MET mutation screening in an independent validation set (n = 26) of PSC were performed.(More)