Germline and Somatic Mutations of the INK4a-ARF Gene in a Xeroderma Pigmentosum Group C Patient
| Autor: | M. Ribojad, Thierry Magnaldo, J. Rivet, Gisele Delestaing, Nicole Basset-Seguin, O. Thibaudeau, Nadem Soufir, Alain Sarasin, Leela Daya-Grosjean |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Keratinocytes
Male Pathology medicine.medical_specialty congenital hereditary and neonatal diseases and abnormalities Xeroderma pigmentosum Skin Neoplasms DNA Repair DNA Mutational Analysis lymphoma p14ARF Dermatology Biology medicine.disease_cause Lymphoma T-Cell Biochemistry Germline Germline mutation Tumor Suppressor Protein p14ARF medicine Ultraviolet light Humans Basal cell carcinoma Child skin and connective tissue diseases Molecular Biology Cyclin-Dependent Kinase Inhibitor p16 Germ-Line Mutation Xeroderma Pigmentosum integumentary system skin carcinogenesis Atypical fibroxanthoma nutritional and metabolic diseases Keratosis Cell Biology medicine.disease DNA-Binding Proteins p16INK4A Carcinoma Basal Cell Cancer research Carcinoma Squamous Cell mutation Tumor Suppressor Protein p53 Carcinogenesis Nucleotide excision repair |
| Zdroj: | Journal of Investigative Dermatology. 119(6):1355-1360 |
| ISSN: | 0022-202X |
| DOI: | 10.1046/j.1523-1747.2002.19603.x |
| Popis: | Xeroderma pigmentosum is an inheritable autosomal recessive DNA repair deficient syndrome characterized by a high predisposition to skin cancers. An elevated proportion of tumors from xeroderma pigmentosum patients harbor ultraviolet-induced mutations (CC:GG > TT:AA tandem transitions) of the p53 and/or the INK4a-ARF genes. Here, we report the clinical and molecular features of a 12 y old xeroderma pigmentosum patient who, in addition to severe cutaneous clinical symptoms, also had three unusual tumors, a mediastinal lymphoblastic lymphoma, an atypical fibroxanthoma, and an epithelioid hemangioma. Single strand conformation polymorphism and sequencing analysis of the p53 and INK4a-ARF genes were carried out in DNA from normal skin and different tumors (four actinic keratosis, two microinvasive squamous cell carcinomas, one basal cell carcinoma, and one atypical fibroxanthoma) from the patient. After characterization of the xeroderma pigmentosum C complementation group, we found unexpectedly that this patient also carried a germline mutation of the INK4a-ARF locus affecting the p16INK4A reading frame. Three different somatic mutations that all harbor the signature of ultraviolet light (two of p16INK4A and one of p53) were also detected in the basal cell carcinoma. We hypothesize that the germline mutation of p16INK4A, in association with the nucleotide excision repair defect, could explain the patient's unusual phenotype. Furthermore, this study confirms that concomitant somatic mutations of INK4a-ARF and p53 occur in some xeroderma pigmentosum associated tumors, and seem to accumulate during tumor progression rather than the initiation step. |
| Databáze: | OpenAIRE |
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