Hereditary TP53 codon 292 and somatic P16(INK4A) codon 94 mutations in a Li-Fraumeni syndrome family
Cancer Genetics and Cytogenetics, cilt.113, sa.2, ss.145-151, 1999 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 113 Sayı: 2
- Basım Tarihi: 1999
- Doi Numarası: 10.1016/s0165-4608(98)00276-3
- Dergi Adı: Cancer Genetics and Cytogenetics
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
- Sayfa Sayıları: ss.145-151
- Sağlık Bilimleri Üniversitesi Adresli: Hayır
Özet
Li-Fraumeni syndrome is an autosomal dominant disorder that is characterized by various types of cancer in childhood and adult cases. Although hereditary TP53 mutation is very rare in different human cancers, it has been frequently reported in Li-Fraumeni syndrome. On the other hand, hereditary mutations of TP57(KIP2), P15(INK4B), and P16(INK4A), which affect the cell cycle similar to TP53, were observed in some types of cancer. In a Turkish family with the diagnosis of Li-Fraumeni syndrome, we analyzed the mutation pattern of TP53, P57(KIP2), P15(INK4B), and P16(INK4A) in the peripheral blood, and loss of heterozygosity (homo/hemizygous deletion) pattern of TP53 and P15(INK4B)/P16(INK4A) in two tumor tissues. The propositus had a seminoma, his daughter a medulloblastoma, and one of his healthy cousins, a TP53 codon 292 missense point mutation (AAA→ATA; Lys→Ile) in the peripheral blood cells. Tumor tissue obtained from the propositus with the seminoma revealed loss of heterozygosity in the TP53 gene. In the analyses of tumor tissues from the propositus and his daughter, a P16(INK4A) codon 94 missense point mutation (GCG→GAG; Ala→Glu) was observed with the hereditary TP53 mutation. P16(INK4A) codon 94 mutation observed in our family is a novel mutation in Li-Fraumeni syndrome. No other gene alteration in TP53, P57(KIP2), P15(INK4B), and P16(INK4A) was observed. Existence of the P16(INK4A) mutation and the hereditary TP53 mutation with or without loss of heterozygosity in the TP53 gene (seminoma/medulloblastoma) may be evidence for a common mechanism involved in tumorogenesis. The gene alterations in TP53 and P16(INK4A) genes may be used as tumor markers in our family. Copyright (C) 1999 Elsevier Science Inc.