Functional pri-miR-34b/c rs4938723 and KRAS 3'UTR rs61764370 SNPs: Novel phenotype modifiers in Li-Fraumeni Syndrome?

Purpose: Li-Fraumeni Syndrome (LFS) is a rare cancer predisposing condition caused by germline pathogenic TP53 variants, in which core tumors comprise sarcomas, breast, brain and adrenocortical neoplasms. Clinical manifestations are highly variable in carriers of the Brazilian germline founder variant TP53 p.R337H, possibly due to the influence of modifier genes such as miRNA genes involved in the regulation of the p53 pathway.

Primary cells derived from Tuberous Sclerosis Complex patients show autophagy alteration in the haploinsufficiency state.

Tuberous sclerosis complex (TSC) is an autosomal dominant cancer predisposition disorder caused by heterozygous mutations in TSC1 or TSC2 genes and characterized by mTORC1 hyperactivation. TSC-associated tumors develop after loss of heterozygosity mutations and their treatment involves the use of mTORC1 inhibitors. We aimed to evaluate cellular processes regulated by mTORC1 in TSC cells with different mutations before tumor development.

The paradox of autophagy in Tuberous Sclerosis Complex.

Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder caused by germline mutations in TSC1 or TSC2 genes, which leads to the hyperactivation of the mTORC1 pathway, an important negative regulator of autophagy. This leads to the development of hamartomas in multiple organs. The variability in symptoms presents a challenge for the development of completely effective treatments for TSC.

Tuberous Sclerosis Complex with rare associated findings in the gastrointestinal system: a case report and review of the literature.

Background: Tuberous Sclerosis Complex (TSC) is a complex and heterogeneous genetic disease that has well-established clinical diagnostic criteria. These criteria do not include gastrointestinal tumors.

Case Presentation: We report a 45-year-old patient with a clinical and molecular diagnosis of TSC and a family history of cancer, presenting two rare associated findings: gastrointestinal polyposis and pancreatic neuroendocrine tumor.

Systems Biology Approaches Reveal Potential Phenotype-Modifier Genes in Neurofibromatosis Type 1.

Neurofibromatosis type (NF1) is a syndrome characterized by varied symptoms, ranging from mild to more aggressive phenotypes. The variation is not explained only by genetic and epigenetic changes in the gene and the concept of phenotype-modifier genes in extensively discussed in an attempt to explain this variability. Many datasets and tools are already available to explore the relationship between genetic variation and disease, including systems biology and expression data.

MIR605 rs2043556 is associated with the occurrence of multiple primary tumors in TP53 p.(Arg337His) mutation carriers.

Li-Fraumeni and Li-Fraumeni-like (LFS/LFL) Syndrome are cancer predisposition syndromes caused by germline pathogenic variants in TP53 and are associated with an increased risk of multiple early-onset cancers. In Southern and Southeastern Brazil, a germline founder variant with partial penetrance located in the oligomerization domain of TP53, c.1010G>A p.

The Role of Co-Deleted Genes in Neurofibromatosis Type 1 Microdeletions: An Evolutive Approach.

Neurofibromatosis type 1 (NF1) is a cancer predisposition syndrome that results from dominant loss-of-function mutations mainly in the gene. Large rearrangements are present in 5-10% of affected patients, generally encompass neighboring genes, and are correlated with a more severe NF1 phenotype. Evident genotype-phenotype correlations and the importance of the co-deleted genes are difficult to establish.