Project description:This is a pathogenic mutation profile of colorectal patients specifically in 5 genes, i.e. APC, TP53, PIK3CA, KRAS, and MLH1. Single nucleotide variants identified were synchronized with patients’ characteristics.
Project description:The p53 tumor suppressor binds DNA cooperatively as a tetramer, mediated by salt-bridge interactions between p53 residues E180 and R181. Variants at the R181 residue are one of the most commonly identified TP53 pathogenic variants by germline genetic testing. We show that families with TP53 p.R181H and p.R181C variants show an attenuated cancer risk phenotype compared to patients with classic Li Fraumeni Syndrome due to hotspot loss of function variants. Despite this phenotype, we find that p53 R181H and R181C variants have reduced ability to bind to p53 promotor target sequences and transactivate p53 target genes. We further show that p53 R181H and R181C retain wild-type p53 structure and tetramerization. In addition, R181-mutant cells undergo apoptosis through wild-type p53 activity at the mitochondria. These results indicate that retention of transcription-independent p53 tumor suppressor function may result in a reduced penetrance cancer risk syndrome in humans.
Project description:BRCA1, BRCA2, TP53 germline and somatic variants and clinicopathological characteristics of Brazilian patients with epithelial ovarian cancer
Project description:Gene expression profiling of immortalized human mesenchymal stem cells with hTERT/E6/E7 transfected MSCs. hTERT may change gene expression in MSCs. Goal was to determine the gene expressions of immortalized MSCs.
Project description:We identified pathogenic and likely pathogenic variants in 17.8% of the patients within a wide range of cancer types. In particular, mesothelioma, ovarian cancer, cervical cancer, urothelial cancer, and cancer of unknown primary origin displayed high frequencies of pathogenic variants. In total, 22 BRCA1 and BRCA2 germline variant were identified in 12 different cancer types, of which 10 (45%) variants were not previously identified in these patients. Pathogenic germline variants were predominantly found in DNA repair pathways; approximately half of the variants were within genes involved in homologous recombination repair. Loss of heterozygosity and somatic second hits were identified in several of these genes, supporting possible causality for cancer development. A potential treatment target based on pathogenic germline variant could be suggested in 25 patients (4%).
