P53 p63 t cell lymphoma

p53 is the most frequently mutated gene in human cancers and mutant p53 has a gain of function (GOF) that promotes tumor progression and therapeutic resistance. One of the major GOF activities of mutant p53 is to suppress 2 other p53 family proteins, p63 and p73. However, the molecular basis is not fully understood. Here, we examined whether mutant p53 antagonizes p63/p73-mediated tumor suppression in vivo by using mutant p53-R270H knockin and TAp63/p73 -deficient mouse models. We found that knockin mutant p53-R270H shortened the life span of p73 +/- mice and subjected TAp63 +/- or p73 +/- mice to T lymphoblastic lymphomas (TLBLs)...

ERG (avian v-ets erythroblastosis virus E26 oncogene homolog), an oncoprotein in prostate carcinoma and Ewing's sarcoma is associated with poor prognosis in patients with acute myeloid leukemia and T lymphoblastic leukemia. However little is known about ERG in lymphoma. Here we studied ERG in diffuse large B-cell lymphoma (DLBCL) by immunohistochemistry, fluorescence in situ hybridization (FISH), genome-wide microRNA (miRNA) expression profiling, real-time reverse-transcriptase polymerase chain reaction (RT-PCR) and whole exome sequencing (WES)...

BACKGROUND: The purpose of this study was to investigate whether gastroduodenal reflux can play a role in the pathogenesis of hypopharyngeal cancer; therefore, we assessed its effect on the nuclear factor-kappa B (NF-κB) pathway, as similarly noted in the esophagus. METHODS: We exposed human cells derived from the hypopharyngeal epithelium to bile acids or deoxycholic acid. We centered our study on the transcriptional activation of NF-κB pathway, previously linked to head and neck squamous cell carcinoma (HNSCC)...

The TP63 gene encodes a member of the p53 family of transcription factors. Although TP53 is a well-known tumor suppressor gene, the role of p63 in tumorigenesis is controversial. Our group recently identified novel chromosomal rearrangements involving TP63 in approximately 6% of peripheral T-cell lymphomas, which correlated with a p63+/p40- immunohistochemical profile. As a subset of lung adenocarcinomas are p63+/p40-, we undertook the current study to examine the presence of TP63 rearrangements and correlate with p63/p40 expression...

PURPOSE OF REVIEW: Anaplastic large cell lymphomas (ALCLs) are rare entities whose somatic genetic lesions have been identified only in a subset of patients. Thus, an integrated and massive discovery programme is required to define their tumourigenic alterations and to design more successful tailored therapies. RECENT FINDINGS: The discovery of anaplastic lymphoma kinase (ALK) fusions has provided the basis for the characterization of distinct subsets among ALCL patients...

OBJECTIVES: To investigate the pathological and clinical meaning of p63 in extranodal nasal type NK/T cell lymphoma (NKTCL). METHODS: We detected p63 and p53 expression using immunohistochemistry staining in 84 cases of NKTCL from Southern of China, an area with a well known high incidence of nasopharyngeal carcinoma, which is closely associated with Epstein-Barr virus infection. Moreover, we analysed the relationship between p63 and p53 expression and the clinicopathological features of NKTCL...

Peripheral T-cell lymphomas (PTCLs) are aggressive malignancies of mature T lymphocytes with 5-year overall survival rates of only ∼ 35%. Improvement in outcomes has been stymied by poor understanding of the genetics and molecular pathogenesis of PTCL, with a resulting paucity of molecular targets for therapy. We developed bioinformatic tools to identify chromosomal rearrangements using genome-wide, next-generation sequencing analysis of mate-pair DNA libraries and applied these tools to 16 PTCL patient tissue samples and 6 PTCL cell lines...

Although the definition of precursor T lymphoblastic lymphoma (T-LBL) is based only on histopathology, most cases cannot be diagnosed only by HE sections. Since 95% of T-LBL expresses TdT and TdT is expressed only in lymphoblasts, immunohistochemical demonstration of TdT is mandatory for the diagnosis of TLBL. However, little is known about the expression of other precursor cell molecules. A 58-year-old woman with myelodysplastic syndrome (RAEB) became overt acute myelogenous leukemia (AML). She was treated twice with allogeneic peripheral blood stem cell transplantation from her son...

BACKGROUND: Aberrant activation of beta-catenin contributes to the onset of a variety of tumours. There are many tumours that display beta-catenin accumulation in the absence of mutations in its gene. Recently, abnormal accumulation of wild-type beta-catenin has been associated with mutational inactivation of the p53 tumour suppressor. OBJECTIVES: To investigate the potential role of p53 and its homologue p63 in beta-catenin deregulation and to correlate this with disease outcome...

p63 is a recently described p53 homologue. It is involved in survival and differentiation of reserve/stem cells in epithelia. To obtain new insights into the role of p63 in malignant lymphomas (MLs), immunohistochemical staining for p63 and p53 was performed in 126 cases of MLs. p63 was expressed in 38 cases of MLs (30.2%) including 32/61 cases (52.5%) of diffuse large B-cell lymphoma (DLBCL), 1/8 cases (12.5%) of precursor T-lymphoblastic lymphoma (T-LBL), 4/14 cases (28.6%) of follicular lymphoma, 1/6 cases (16...

p63, a member of the p53 family, is involved in the survival and differentiation of reserve/stem cells in different epithelia. To unveil the possible role of p63 in thymic physiology and pathology, we investigated the expression of p63 isoforms in normal thymus, thymomas and other mediastinal tumours. All samples were analysed using immunohistochemistry with three different antibodies: 4A4 antibody recognising all p63 isoforms, p40 antibody reacting only with truncated dominant-negative isoforms (DeltaN-p63) and H-129 antibody recognising all alpha-isoforms...

The p53 gene is the most frequently mutated gene in human cancer. The identification of two homologues, p63 and p73, revealed that p53 is a member of a family of related transcription factors. Given that they share amino acid sequence identity reaching 63% in the DNA-binding domain, p53, p63 and p73 should have redundant functions in the regulation of gene expression. Indeed, p73 can activate p53-regulated genes and suppress growth or induce apoptosis. Moreover, p53 and p73 are both induced by DNA damage - albeit through distinct mechanisms...