دورية أكاديمية
Association Between INK4a-ARF and p53 Mutations in Skin Carcinomas of Xeroderma Pigmentosum Patients
| العنوان: | Association Between INK4a-ARF and p53 Mutations in Skin Carcinomas of Xeroderma Pigmentosum Patients |
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| المؤلفون: | Soufir, Nadem, Daya-Grosjean, Leela, de La Salmonière, Pauline, Moles, Jean-Pierre, Dubertret, Louis, Sarasin, Alain, Basset-Seguin, Nicole |
| بيانات النشر: | Oxford University Press |
| سنة النشر: | 2000 |
| المجموعة: | HighWire Press (Stanford University) |
| مصطلحات موضوعية: | REPORTS |
| الوصف: | Background: The INK4a-ARF locus encodes two tumor suppressor proteins, p16INK4a and p14ARF, that act through the Rb-CDK4 and p53 pathways, respectively. Data from murine models and sporadic human skin carcinomas implicate p16INK4a and p14ARF in the development of skin carcinomas. We examined the frequency of INK4a-ARF, p53, and CDK4 mutations in skin carcinomas from patients with xeroderma pigmentosum (XP), a rare autosomal disease that is associated with a defect in DNA repair and that predisposes patients to skin cancer. Methods: DNA from skin cancers of 28 unrelated XP patients was screened for mutations in p53, INK4a-ARF, and CDK4 coding exons by single-strand conformation polymorphism analysis and automated sequencing. Data were evaluated with the use of the exact unconditional test derived from Fisher's test. All statistical tests were two-sided. Results: Eight of 28 XP-associated tumors had mutations in the INK4a-ARF locus. Three XP-associated tumors had multiple mutations at this locus. In all, 13 mutations in the INK4a-ARF locus were detected in XP-associated tumors, of which seven (54%) were signature UV radiation-induced mutations, i.e., tandem CC : GG→TT : AA transitions. p53 mutations, mostly of the type induced by UV radiation, were present in 12 tumors (43%). Statistically significant positive associations were found between the frequency of mutations in p53 and in p16INK4a ( P = .008) and between the frequency of mutations in p53 and in p14ARF ( P <.001). No mutations were detected within the CDK4 gene. Conclusions: We have demonstrated for the first time the occurrence of UV radiation-induced mutations in INK4a-ARF in XP-associated skin carcinomas. The simultaneous inactivation of p53 and INK4a-ARF may be linked to the genetic instability caused by XP and could be advantageous for tumor progression. |
| نوع الوثيقة: | text |
| وصف الملف: | text/html |
| اللغة: | English |
| العلاقة: | http://jnci.oxfordjournals.org/cgi/content/short/92/22/1841Test; http://dx.doi.org/10.1093/jnci/92.22.1841Test |
| DOI: | 10.1093/jnci/92.22.1841 |
| الإتاحة: | https://doi.org/10.1093/jnci/92.22.1841Test http://jnci.oxfordjournals.org/cgi/content/short/92/22/1841Test |
| حقوق: | Copyright (C) 2000, National Cancer Institute |
| رقم الانضمام: | edsbas.B46AF482 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1093/jnci/92.22.1841 |
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