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).
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).
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.
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.
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.
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.
Germline mutations in the TP53 gene are detected in approximately 80% of families that fulfill LFS criteria and in 15% to 25% of families that fulfill criteria for Li-Fraumeni-like syndrome (LFS), a group of related syndromes with broader clinical criteria.
However, the prevalence of other tumors of the Li-Fraumeni syndrome (LFS) and Li-Fraumeni-like syndrome (LFL) spectrum, the clinical outcomes and the potential tumor occurrence in relatives carrying this distinct TP53 mutation were not fully investigated.
Targeted, massively parallel DNA sequencing and molecular inversion probe microarray analysis revealed a germline TP53 mutation compatible with Li-Fraumeni-like syndrome, somatic mutations of PIK3CA in the endometrial cancer, and a somatic mutation of GNA11 and JAK3 in the PMM.
Association of germline or somatic TP53 missense mutation with oncogene amplification in tumors developed in patients with Li-Fraumeni or Li-Fraumeni-like syndrome.
The mean in vitro lifespan of dermal fibroblast strains derived from cancer-affected individuals belonging to families conforming to the classical Li-Fraumeni-syndrome or the Li-Fraumeni-like syndrome (LF strains), but in whom no TP53 mutation has been found, was not significantly different to that of normal strains.
Recently CHK2 was functionally linked to the p53 pathway, and mutations in these two genes seem to result in a similar Li-Fraumeni syndrome (LFS) or Li-Fraumeni-like syndrome (LFL) multi-cancer phenotype frequently including breast cancer.
A database has been created to collect information on families carrying a germ-line mutation in the TP53 gene and on families affected with Li-Fraumeni syndromes [Li-Fraumeni syndrome (LFS) and Li-Fraumeni-like syndrome (LFL)].
Germline TP53 mutations predispose to multiple cancers defining Li-Fraumeni/Li-Fraumeni-like syndrome (LFS/LFL), a disease with large individual disparities in cancer profiles and age of onset.
The present study was aimed at searching for germ line mutations of TP53 gene in familial gastric cancer with cluster for Li-Fraumeni syndrome or Li-Fraumeni-like syndrome.