Germline mutations in p53 are the genetic alteration underlying predisposition to multiple cancers in Li-Fraumeni syndrome and Li-Fraumeni-like syndrome.
13 of 18 families with childhood cancer and BRCA1 or BRCA2 mutations (72%) and 13 of 31 families with childhood cancer and negative mutation testing (42%) met the Birch criteria for Li-Fraumeni like syndrome (LFL).
Patients were chosen from cancer families with phenotypes typical for germline mutations of p53 (LFS, LFL), BRCA1 [hereditary breast (ovarian) cancer, HB(O)C] or a complex consistent with both LFL and HB(O)C. Children with leukemia were included in the study as another high risk group (FELIX et al.1992).
Because seven of our BRCA1 and BRCA2 mutation-negative families fulfilled the criteria of either Li-Fraumeni syndrome (LFS) or Li-Fraumeni-like syndrome (LFL), we decided to screen them for germ-line TP53 mutations in exons 5-8 using a dual-temperature single-strand conformation polymorphism assay (SSCP).
13 of 18 families with childhood cancer and BRCA1 or BRCA2 mutations (72%) and 13 of 31 families with childhood cancer and negative mutation testing (42%) met the Birch criteria for Li-Fraumeni like syndrome (LFL).
Because seven of our BRCA1 and BRCA2 mutation-negative families fulfilled the criteria of either Li-Fraumeni syndrome (LFS) or Li-Fraumeni-like syndrome (LFL), we decided to screen them for germ-line TP53 mutations in exons 5-8 using a dual-temperature single-strand conformation polymorphism assay (SSCP).
Among 13 early-onset BC, CSL and LFL patients, gene panel sequencing identified a potentially pathogenic variant in CHEK2 that affects a canonical RNA splicing signal.
In conclusion, our results suggest that MDM2 SNP 309 may contribute to the LFL phenotype and also to an earlier age at diagnosis of ACC and BC cancer in carriers of the R337H founder mutation.
Among 13 early-onset BC, CSL and LFL patients, gene panel sequencing identified a potentially pathogenic variant in CHEK2 that affects a canonical RNA splicing signal.
Among 13 early-onset BC, CSL and LFL patients, gene panel sequencing identified a potentially pathogenic variant in CHEK2 that affects a canonical RNA splicing signal.
Recently, we uncovered a variant in the POT1 gene (p.R117C) as causative of familial cardiac angiosarcomas (CAS) in Li-Fraumeni-like (LFL) syndrome families.
The high Ile(157)--> Thr(157)mutation frequency (6.5%) observed in healthy controls and the lack of other mutations suggest that CHK2 does not contribute significantly to the hereditary breast cancer or LFL-associated breast cancer risk, at least not in the Finnish population.