P53 Germline Mutations and Therapy-related Myelodysplastic Syndrome

Koiti INOKUCHI
2005 Internal medicine (Tokyo. 1992)  
Mutations of the p53 tumor-suppressor gene are important in the multistep process of malignant transformation. Whereas germline p53 mutations such as those observed in cancer-prone families including Li-Fraumeni syndrome (LFS) and LFS-like syndrome (LFL), are very rare; somatically acquired p53 mutations are observed in more than 50% of patients with solid tumors (1, 2). The type and location of p53 germ-line mutations observed in cancer-prone families (LFS/LFL and a family history of cancer:
more » ... ) are now available on the internet at http://www.lf2.cuni.cz (3). Mutations observed in the germ line and in sporadic cases are very similar. In all p53 mutations, about 30% of mutations are clustered in 8 "hotspot" codons (codons 175, 176, 220, 245, 248, 249, 273, and 282) (2). Major mutations in LFS/LFL and FH in the germline have been reported in codons 248 (12%), 273 (11%), 175 (8%), 245 (6%), 282 (5%), 213 (5%), 133 (3%), 152 (3%) and 337 (3%) (2). The present case has a germ line p53 mutation in codon 175 (4). In codon 175 mutations, a missense G to A mutation is the most frequent mutation in LFS/LFL and FH. Unfortunately, the present paper provides no evidence of the same mutation in the sons and relatives of the patient. Although the patient's family history of cancer is obvious, it is unclear whether the present mutation is a proband or an inherited mutation.
doi:10.2169/internalmedicine.44.406 pmid:15942083 fatcat:pcmhbei3hndqvj7uykhf7qmffy