Tags

Type your tag names separated by a space and hit enter

Constitutional mutation in exon 8 of the p53 gene in a patient with multiple primary tumours: molecular and immunohistochemical findings.
Oncogene 1993; 8(5):1269-76O

Abstract

We report a constitutional mutation of codon 273 in exon 8 of the p53 gene. The affected individual has developed multiple independent benign and malignant tumours (tricholemmoma of the scalp, multiple trichoepitheliomata of the face, osteosarcoma of the ovary, bilateral breast cancer, malignant fibrous histiocytoma of the thigh and endometrial adenocarcinoma) and belongs to a family with some, but not all, features of the Li-Fraumeni syndrome. The mutation, found in both blood lymphocyte and tumour specimens, is a cytosine to thymine transition at codon 273, resulting in an amino acid change from arginine to cysteine. The mother and sister of the index case both died of tumours at an early age. We have demonstrated that formalin-preserved material from these tumours contains the same C-->T mutation at codon 273, indicating that this mutation has probably been transmitted through the germline. All tumours from the index case, both benign and malignant, showed immunohistochemical positivity with four antibodies to the p53 protein. Positive staining was also seen in scattered nuclei of morphologically normal epidermal keratinocytes and pilosebaceous cells, but not in lymphocytes or other morphologically normal cells from the index case. However, a similar staining pattern in apparently normal tissue was also observed in 13/48 sections from other individuals with various skin conditions (melanocytic naevi, psoriasis and normal skin adjacent to malignant melanoma and fibrous histiocytomas), suggesting that this pattern of p53 staining may not be unique to individuals with constitutional p53 mutations.

Authors+Show Affiliations

CRC Academic Unit of Radiotherapy and Oncology, Royal Marsden Hospital, Sutton, Surrey, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

8479749

Citation

Eeles, R A., et al. "Constitutional Mutation in Exon 8 of the P53 Gene in a Patient With Multiple Primary Tumours: Molecular and Immunohistochemical Findings." Oncogene, vol. 8, no. 5, 1993, pp. 1269-76.
Eeles RA, Warren W, Knee G, et al. Constitutional mutation in exon 8 of the p53 gene in a patient with multiple primary tumours: molecular and immunohistochemical findings. Oncogene. 1993;8(5):1269-76.
Eeles, R. A., Warren, W., Knee, G., Bartek, J., Averill, D., Stratton, M. R., ... Easton, D. F. (1993). Constitutional mutation in exon 8 of the p53 gene in a patient with multiple primary tumours: molecular and immunohistochemical findings. Oncogene, 8(5), pp. 1269-76.
Eeles RA, et al. Constitutional Mutation in Exon 8 of the P53 Gene in a Patient With Multiple Primary Tumours: Molecular and Immunohistochemical Findings. Oncogene. 1993;8(5):1269-76. PubMed PMID: 8479749.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Constitutional mutation in exon 8 of the p53 gene in a patient with multiple primary tumours: molecular and immunohistochemical findings. A1 - Eeles,R A, AU - Warren,W, AU - Knee,G, AU - Bartek,J, AU - Averill,D, AU - Stratton,M R, AU - Blake,P R, AU - Tait,D M, AU - Lane,D P, AU - Easton,D F, PY - 1993/5/1/pubmed PY - 1993/5/1/medline PY - 1993/5/1/entrez SP - 1269 EP - 76 JF - Oncogene JO - Oncogene VL - 8 IS - 5 N2 - We report a constitutional mutation of codon 273 in exon 8 of the p53 gene. The affected individual has developed multiple independent benign and malignant tumours (tricholemmoma of the scalp, multiple trichoepitheliomata of the face, osteosarcoma of the ovary, bilateral breast cancer, malignant fibrous histiocytoma of the thigh and endometrial adenocarcinoma) and belongs to a family with some, but not all, features of the Li-Fraumeni syndrome. The mutation, found in both blood lymphocyte and tumour specimens, is a cytosine to thymine transition at codon 273, resulting in an amino acid change from arginine to cysteine. The mother and sister of the index case both died of tumours at an early age. We have demonstrated that formalin-preserved material from these tumours contains the same C-->T mutation at codon 273, indicating that this mutation has probably been transmitted through the germline. All tumours from the index case, both benign and malignant, showed immunohistochemical positivity with four antibodies to the p53 protein. Positive staining was also seen in scattered nuclei of morphologically normal epidermal keratinocytes and pilosebaceous cells, but not in lymphocytes or other morphologically normal cells from the index case. However, a similar staining pattern in apparently normal tissue was also observed in 13/48 sections from other individuals with various skin conditions (melanocytic naevi, psoriasis and normal skin adjacent to malignant melanoma and fibrous histiocytomas), suggesting that this pattern of p53 staining may not be unique to individuals with constitutional p53 mutations. SN - 0950-9232 UR - https://www.unboundmedicine.com/medline/citation/8479749/Constitutional_mutation_in_exon_8_of_the_p53_gene_in_a_patient_with_multiple_primary_tumours:_molecular_and_immunohistochemical_findings_ DB - PRIME DP - Unbound Medicine ER -