No TP53 mutations in neuroblastomas detected by PCR-SSCP

Castresana, Javier S.; Bello, M. Josefa; Rey, Juan A.; Nebreda, Paloma; Queizán, A; García-Miguel, Furificación; Pestaña, Ángel

doi:10.1016/0165-4608(94)90357-3

Cited by 8 publications

(10 citation statements)

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“…We performed sequence analysis for mutations in the TP53 coding region in 40 NB tumors but did not find any mutation. This is in concordance with other studies that have not detected any, or as few as 2%, TP53 mutations in NB tumors (Vogan et al, 1993;Castresana et al, 1994;Imamura et al, 1993).…”

Section: Discussionsupporting

confidence: 93%

Reduced levels of miR‐34a in neuroblastoma are not caused by mutations in the TP53 binding site

Feinberg-Gorenshtein

Avigad

Jeison

et al. 2009

Genes Chromosomes & Cancer

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Neuroblastoma (NB) is the most common extracranial solid tumor in children below the age of 5 years. miR-34a, located in chromosome band 1p36, has been recently implicated as a tumor suppressor gene in NB. In addition, it has been shown that miR-34a is activated by TP53 by binding to a TP53 binding site upstream to the mature miR-34a. We studied NB tumors from 57 patients for miR-34a expression levels, 1p status, mutations in the TP53 coding region and mutations of the TP53 binding site. Reduced expression levels of miR-34a were identified in tumors harboring 1p36.3 Loss (P = 0.028). No mutations were identified in the coding region of TP53, or in the TP53 binding site. Thus, mutations in the binding site are not an additional mechanism for the inactivation of miR-34a in NB. Other regulatory mechanisms controlling miR-34a expression and its relationship to TP53 should be further explored.

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Section: Discussionsupporting

confidence: 93%

Reduced levels of miR‐34a in neuroblastoma are not caused by mutations in the TP53 binding site

Feinberg-Gorenshtein

Avigad

Jeison

et al. 2009

Genes Chromosomes & Cancer

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“…Three mutations were located outside the classic hot-spot region (exons 5-9), indicating that p53 mutations are best identified by sequencing the entire coding region. The observed mutation frequency in our cell line panel (26%) is considerably higher than the p53 mutation rate of approximately 1% that was found in early studies of neuroblastoma tumors (22)(23)(24)(25)(26)(27). This may reflect the fact that cell lines are frequently derived from progressive or relapsed tumors, as p53 mutations can develop during chemotherapy and malignant progression of neuroblastoma (28).…”

Section: Discussionmentioning

confidence: 52%

Functional Analysis of the p53 Pathway in Neuroblastoma Cells Using the Small-Molecule MDM2 Antagonist Nutlin-3

Maerken

Rihani

Dreidax

et al. 2011

Molecular Cancer Therapeutics

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Suppression of p53 activity is essential for proliferation and survival of tumor cells. A direct p53-activating compound, nutlin-3, was used in this study, together with p53 mutation analysis, to characterize p53 pathway defects in a set of 34 human neuroblastoma cell lines. We identified 9 cell lines (26%) with a p53 loss-offunction mutation, including 6 missense mutations, 1 nonsense mutation, 1 in-frame deletion, and 1 homozygous deletion of the 3 0 end of the p53 gene. Sensitivity to nutlin-3 was highly predictive of absence of p53 mutation. Signaling pathways downstream of p53 were functionally intact in 23 of 25 cell lines with wild-type p53. Knockdown and overexpression experiments revealed a potentiating effect of p14 ARF expression on the response of neuroblastoma cells to nutlin-3. Our findings shed light on the spectrum of p53 pathway lesions in neuroblastoma cells, indicate that defects in effector molecules downstream of p53 are remarkably rare in neuroblastoma, and identify p14 ARF as a determinant of the outcome of the response to MDM2 inhibition. These insights may prove useful for the clinical translation of evolving strategies aimed at p53 reactivation and for the development of new therapeutic approaches. Mol Cancer Ther; 10(6); 983-93. Ó2011 AACR.

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“…For instance, N-myc oncogene amplification correlates with advanced disease stage [1], the expression of the Haras [2] and src oncogenes [3] correlates significantly with a better overall prognosis, and inverse relationships between expression of N-myc and nerve growthfactor receptor [4] and between N-myc amplification and trk oncogene expression [5] seem to show that some molecular parameters may be useful prognostic indicators of neuroblastoma behavior. On the other hand, p53 is an exception, as it does not seem to be involved in neuroblastoma: we have demonstrated, by polymerase chain reaction (PCR)-singlestrand conformation polymorphism (SSCP) analysis, that the p53 gene is not mutated in exons 5-8 [6] in 29 neuroblastomas, and we did not detect p53 expression by immunohistochemical analysis, in 16 neuroblastomas.…”

Section: Introductionmentioning

confidence: 70%

“…p53-mutated sarcomas [17] were used at the beginning of this study as positive controls. In the past, we have used the isotopic approach for SSCP determination, using big gels (33 cm × 42 cm × 0.4 mm) containing 6% or 4.5% polyacrylamide (20:1 or 49:1 acrylamide:bis-acrylamide) with or without 10% glycerol [6,[17][18][19][20]. At the beginning of this study, we decided to explore the p16 gene for mutations by a non-isotopic method using a silverstaining technique.…”

Section: Resultsmentioning

confidence: 99%

Mutational analysis of the p16 gene in human neuroblastomas

et al. 1997

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Neuroblastoma is one of the most frequent tumors in infancy. We analyzed 26 neuroblastomas, two ganglioneuromas, and a neuroblastoma metastasis for mutations and homozygous deletions of the p16 (or MTS1 or CDKN2) gene by means of the polymerase chain reaction (PCR) in combination with the single-strand conformation polymorphism (SSCP) technique and by multiplex PCR analysis. We detected mobility shifts in the SSCP gels in seven cases in the 3 half of exon 2 (named exon 2C) of the p16 gene. By PCR amplification of this particular region and SacII restriction enzyme digestion, we confirmed that those cases had a known polymorphism at codon 140 of the p16 gene. Neither mutations nor homozygous deletions were detected. Our results confirm those of Beltinger et al. (Cancer Res 55:2053-2055, 1995), which showed no p16 mutations or homozygous deletions in 18 primary neuroblastomas and nine tumor-derived cell lines. We conclude that the common pattern of p16 inactivation by homozygous deletion or mutation does not seem to be relevant to the development of neuroblastomas.

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No TP53 mutations in neuroblastomas detected by PCR-SSCP

Cited by 8 publications

References 0 publications

Reduced levels of miR‐34a in neuroblastoma are not caused by mutations in the TP53 binding site

Reduced levels of miR‐34a in neuroblastoma are not caused by mutations in the TP53 binding site

Functional Analysis of the p53 Pathway in Neuroblastoma Cells Using the Small-Molecule MDM2 Antagonist Nutlin-3

Mutational analysis of the p16 gene in human neuroblastomas

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