The transcriptional coactivator MN1 has been identified as a gene overexpressed in certain types of human acute myeloid leukemia. Overexpression of this gene is associated with all inv (16) AML, retinoic acid-resistance, a worse prognosis as well as a shorter survival in AML patients with a normal karyotype. This article reviews the role of MN1 in acute myeloid leukemia including MN1 gene structure and action mechanism, MN1-TEL and AML with normal karyotype, MN1 and inv (16) AML, MN1 and retinoic ocid-resistance, and so on.
Humans ; Leukemia, Myeloid, Acute ; genetics ; Oncogene Proteins, Fusion ; genetics ; Transcription Factors ; genetics ; Tumor Suppressor Proteins ; genetics

Glioblastoma ; genetics ; metabolism ; Humans ; Mutation ; Oncogene Proteins ; genetics ; metabolism ; Tumor Suppressor Proteins ; genetics ; metabolism

OBJECTIVETo investigate the hypermethylation status of blu gene promoter in nasopharyngeal NK/T cell lymphoma and its role in the tumorigenesis and molecular diagnosis of this lymphoma.

METHODSTwenty cases of paraffin-embedded nasopharyngeal NK/T cell lymphomas tissues were studied by using methylation specific PCR (MSP).

RESULTSHypermethylation of blu gene promoter is detected in 6 of 20 (30%) nasopharyngeal NK/T cell lymphoma. The 6 positive cases were 4 in 15 nasopharyngeal NK cell lymphomas, 1 of 2 NK like T cell lymphoma and 1 in 3 peripheral T cell lymphomas (unspecified type).

CONCLUSIONHypermethylation of blu gene promoter in nasopharyngeal NK/T cell lymphoma indicated the inactivation of blu gene and its possible role in the tumorigenesis of this lymphoma. blu gene methylation could be detected in paraffin-embedded tissue and used as a new molecular marker for the diagnosis of this lymphoma.

DNA Methylation ; Genes, Tumor Suppressor ; Humans ; Lymphoma ; genetics ; pathology ; Nasopharyngeal Neoplasms ; genetics ; pathology ; Polymerase Chain Reaction ; methods ; Tumor Suppressor Proteins

OBJECTIVE: To screen for small molecular compounds with selective inhibitory activity against cutaneous melanoma cells with BAP1 deletion. METHODS: Cutaneous melanoma cells expressing wild-type BAP1 were selected to construct a BAP1 knockout cell model using CRISPR-Cas9 system, and small molecules with selective inhibitory activity against BAP1 knockout cells were screened from a compound library using MTT assay. Rescue experiment was carried out to determine whether the sensitivity of BAP1 knockout cells to the candidate compounds was directly related to BAP1 deletion. The effects of the candidate compounds on cell cycle and apoptosis were detected with flow cytometry, and the protein expressions in the cells were analyzed with Western blotting. RESULTS: The p53 activator RITA from the compound library was shown to selectively inhibit the viability of BAP1 knockout cells. Overexpression of wild-type BAP1 reversed the sensitivity of BAP1 knockout cells to RITA, while overexpression of the mutant BAP1 (C91S) with inactivated ubiquitinase did not produce any rescue effect. Compared with the control cells expressing wild-type BAP1, BAP1 knockout cells were more sensitive to RITA-induced cell cycle arrest and apoptosis (P < 0.0001) and showed an increased expression of p53 protein, which was further increased by RITA treatment (P < 0.0001). CONCLUSION Loss of BAP1 results in the sensitivity of cutaneous melanoma cells to p53 activator RITA. In melanoma cells, the activity of ubiquitinase in BAP1 is directly related to their sensitivity to RITA. An increased expression of p53 protein induced by BAP1 knockout is probably a key reason for RITA sensitivity of melanoma cells, suggesting the potential of RITA as a targeted therapeutic agent for cutaneous melanoma carrying BAP1-inactivating mutations.
Humans ; Melanoma ; Skin Neoplasms ; Tumor Suppressor Protein p53 ; Apoptosis ; Cell Division ; Tumor Suppressor Proteins/genetics* ; Ubiquitin Thiolesterase/genetics*

Asian Continental Ancestry Group ; Exons ; genetics ; Humans ; Mutation ; Tuberous Sclerosis ; genetics ; Tumor Suppressor Proteins ; genetics

The promyelocytic leukemia (PML) was originally identified and named as acute promyelocytic leukaemia (APL) . The PML, encoded by PML gene, locates in the nuclear body (NB) and shuttles in the cell nucleus-cytoplasm, so that PML completes many regulation functions. There are many research on the function of nuclear PML, but in recent years the foreign data indicate that cytoplasmic PML gene plays an important role in hematologic malignancies and solid tumors. In this article, the biological functions of PML gene in cytoplasm are reviewed.
Cytoplasm ; genetics ; Humans ; Leukemia, Promyelocytic, Acute ; genetics ; Nuclear Proteins ; genetics ; Promyelocytic Leukemia Protein ; Transcription Factors ; genetics ; Tumor Suppressor Proteins ; genetics

CKLF-like MARVEL transmembrane domain containing member(CMTM)is a novel generic family firstly reported by Peking University Center for Human Disease Genomics. CMTM5 belongs to this family and has exhibited tumor-inhibiting activities. It can encode proteins approaching to the transmembrane 4 superfamily(TM4SF). CMTM5 is broadly expressed in normal adult and fetal human tissues, but is undetectable or down-regulated in most carcinoma cell lines and tissues. Restoration of CMTM5 may inhibit the proliferation, migration, and invasion of carcinoma cells. Although the exact mechanism of its anti-tumor activity remains unclear, CMTM5 may be involved in various signaling pathways governing the occurrence and development of tumors. CMTM5 may be a new target in the gene therapies for tumors, while further studies on CMTM5 and its anti-tumor mechanisms are warranted.
Chemokines ; genetics ; metabolism ; Humans ; MARVEL Domain-Containing Proteins ; genetics ; metabolism ; Neoplasms ; genetics ; metabolism ; Signal Transduction ; Tumor Suppressor Proteins ; genetics ; metabolism

OBJECTIVETo analyze the mutation of TSC gene in two sporadic patients with tuberous sclerosis complex (TSC).

METHODSAll the coding exons of TSC1 and TSC2 genes of these two patients, unaffected member in the two families, and 100 unrelated population-matched controls were amplified by polymerase chain reaction. The products were analyzed by direct sequencing.

RESULTTwo TSC2 gene mutations (c. 268C > T, c. 5 227C > T) were identified in two patients, but not in their family members and in 100 unrelated population-matched controls.

CONCLUSIONThese two mutations are the cause of the clinical phenotypes of these two sporadic patients with TSC.

Genetic Association Studies ; Humans ; Mutation ; Tuberous Sclerosis ; genetics ; Tumor Suppressor Proteins ; genetics

RASSF1A gene cloned from 3p21.3 region is a novel candidate tumor suppressor gene. The aberrant methylation of CpG lands in the promoter region is the major inactivation mechanism of RASSF1A, and is significantly involved in the genesis and development of multiple solid tumors including prostate cancer. The methylation status examination of RASSF1A could serve as an important technique for the early diagnosis of prostate cancer, while methylation inhibitor is likely to become a novel therapeutic agent.
DNA Methylation ; Early Diagnosis ; Humans ; Male ; Prostatic Neoplasms ; diagnosis ; genetics ; Tumor Suppressor Proteins ; genetics

High-throughput sequencing was performed for the peripheral blood DNA from two probands in the family with tuberous sclerosis complex (TSC) to determine the sequences of TSC-related genes TSC1 and TSC2 and their splicing regions and identify mutation sites. Amplification primers were designed for the mutation sites and polymerase chain reaction and Sanger sequencing were used to verify the sequences of peripheral blood DNA from the probands and their parents. The two probands had c.3981-3982 insA (p.Asp1327AspfsX87) and c.4013-4014 delCA (p.Ser1338Cysfs) heterozygous mutations, respectively, in the TSC2 gene. The parents of proband 1 had no abnormalities at these two loci; the mother of proband 2 had c.4013-4014 delCA heterozygous mutation in the TSC2 gene, while the father and the grandparents of proband 2 had no abnormalities. c.3981-3982 insA mutation may cause early coding termination of amino acid sequence at the 1413th site, and c.4013-4014 delCA mutation may cause early coding termination of amino acid sequence at the 1412th site. These two mutations are the pathogenic mutations for families 1 and 2, respectively, and both of them are novel frameshift mutations, but their association with the disease needs to be further verified by mutant protein function cell model and animal model.
Child ; Child, Preschool ; Female ; Frameshift Mutation ; Humans ; Tuberous Sclerosis ; genetics ; Tumor Suppressor Proteins ; genetics