MDM2 Inhibitor Nutlin-3a Induces Apoptosis and Senescence in Cutaneous T-Cell Lymphoma: Role of p53

Manfè, Valentina; Biskup, Edyta; Johansen, Peter; Kamstrup, Maria R.; Krejsgaard, Thorbjørn; Morling, Niels; Wulf, Hans Christian; Gniadecki, Robert

doi:10.1038/jid.2012.10

Cited by 42 publications

(41 citation statements)

References 61 publications

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“…However, previous studies and our own revealed an absence of p53 in resting Mac-1 cells, 28 and it was not affected by SATB1 suppression ( Figure 3B). Given the high potency of SATB1 as a transcription factor, we postulate that SATB1 may directly regulate CDKN1A transcription in PCALCL cells.…”

Section: Satb1 Regulates P21 Expression By Directly Inhibiting Cdkn1amentioning

confidence: 67%

SATB1 overexpression promotes malignant T-cell proliferation in cutaneous CD30+ lymphoproliferative disease by repressing p21

Wei

Zhang

et al. 2014

Blood

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Section: Satb1 Regulates P21 Expression By Directly Inhibiting Cdkn1amentioning

confidence: 67%

SATB1 overexpression promotes malignant T-cell proliferation in cutaneous CD30+ lymphoproliferative disease by repressing p21

Wei

Zhang

et al. 2014

Blood

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“…Also, 30 patients had MF stage IIB or higher, and tissue for p53 analysis was available in 19 cases (Table 1). Control materials included CTCL cell lines SeAx, MyLa200, and MF1885, together with biopsies from solid tumors with known p53 mutations (19). …”

Section: Methodsmentioning

confidence: 99%

TP53 Gene Status Affects Survival in Advanced Mycosis Fungoides

et al. 2016

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TP53 is frequently mutated in different types of neoplasms including leukemia and lymphomas. Mutations of TP53 have also been reported in mycosis fungoides (MF), the most common type of cutaneous lymphoma. However, little is known about the frequency, spectrum of mutations, and their prognostic significance in MF. In this study, we have optimized the protocol for Sanger sequencing of TP53 using DNA extracted from archival paraffin-embedded biopsies. Of 19 samples from patients with stage IIB MF or higher, 31% harbored mutations in TP53. Overall survival of the patients with mutated TP53 was significantly shorter than median survival in the age- and stage-matched patients treated in our Institution. Distribution of mutations was heterogenous in TP53 exons; however, C > T transitions were common suggesting the causal role of ultraviolet radiation. We propose that TP53 mutation status would be useful for risk stratification of patients with advanced MF.

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“…In the negative case (case #6), the immunohistochemical negativity may be explained by the fact that the R196Stop mutation likely prevents p53 stabilization, as reported in the HuT-78 T-lymphoma cell line harboring the same homozygous nonsense TP53 R196Stop mutation [14].…”

Section: Mutation In Matched Hg-ien and Egc Lesionsmentioning

confidence: 99%

High-throughput mutation profiling identifies novel molecular dysregulation in high-grade intraepithelial neoplasia and early gastric cancers

et al. 2013

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Background There is still no widely accepted molecular marker available to distinguish between gastric high-grade intraepithelial neoplasia (HG-IEN) and invasive early gastric cancer (EGC). Methods HG-IEN and EGC lesions coexisting in the same patient were manually microdissected from a series of 15 gastrectomies for EGC; 40 ng DNA was used for multiplex PCR amplification using the Ion AmpliSeq Cancer Panel, which explores the mutational status of hotspot regions in 50 cancer-associated genes. Results Of the 15 EGCs, 12 presented at least one somatic mutation among the 50 investigated genes, and 6 of these showed multiple driver gene somatic mutations. TP53 mutations were observed in 9 cases; APC mutations were identified in 3 cases; and ATM and STK11 were mutated in 2 cases. Seven HG-IEN lesions shared an identical mutational profile with the EGC from the same patient; 13 mutations observed in APC, ATM, FGFR3, PIK3CA, RB1, STK11, and TP53 genes were shared by both HG-IEN and ECG lesions. CDKN2A, IDH2, MET, and RET mutations were observed only in EGC. TP53 deregulation was further investigated in an independent series of 75 biopsies corresponding to all the phenotypic lesions occurring in the EGC carcinogenetic cascade. p53 nuclear immunoreaction progressively increased along with the dedifferentiation of the lesions (P \ 0.001). Overall, 18 of 20 p53-positive lesions showed a TP53 mutated gene. Discussion Our results support the molecular similarity between HG-IEN and EGC and suggest a relevant role for TP53 in the progression to the invasive phenotype and the use of immunohistochemistry as a surrogate to detect TP53 gene mutations.

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MDM2 Inhibitor Nutlin-3a Induces Apoptosis and Senescence in Cutaneous T-Cell Lymphoma: Role of p53

Cited by 42 publications

References 61 publications

SATB1 overexpression promotes malignant T-cell proliferation in cutaneous CD30+ lymphoproliferative disease by repressing p21

SATB1 overexpression promotes malignant T-cell proliferation in cutaneous CD30+ lymphoproliferative disease by repressing p21

TP53 Gene Status Affects Survival in Advanced Mycosis Fungoides

High-throughput mutation profiling identifies novel molecular dysregulation in high-grade intraepithelial neoplasia and early gastric cancers

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