TY - JOUR
T1 - Constitutional mutation in exon 8 of the p53 gene in a patient with multiple primary tumours
T2 - Molecular and immunohistochemical findings
AU - 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.
AU - Yarnold, J. R.
AU - Cooper, C. S.
AU - Sloane, J. P.
PY - 1993
Y1 - 1993
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 tricho-epitheliomata of the face, osteosarcoma of the ovary, bilateral breast cancer, maligant 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.
AB - 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 tricho-epitheliomata of the face, osteosarcoma of the ovary, bilateral breast cancer, maligant 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.
UR - http://www.scopus.com/inward/record.url?scp=0027223409&partnerID=8YFLogxK
M3 - Article
C2 - 8479749
AN - SCOPUS:0027223409
VL - 8
SP - 1269
EP - 1276
JO - Oncogene
JF - Oncogene
SN - 0950-9232
IS - 5
ER -