A5018120409- Genetic factors in colorectal cancer
- Cancer Genomics and Diagnostics
- Colorectal Cancer Screening and Detection
- Colorectal Cancer Treatments and Studies
- DNA Repair Mechanisms
- RNA Research and Splicing
- Multiple and Secondary Primary Cancers
- Digestive system and related health
- BRCA gene mutations in cancer
- Colorectal and Anal Carcinomas
- Cancer Cells and Metastasis
- Wnt/β-catenin signaling in development and cancer
- Genetic Associations and Epidemiology
- PARP inhibition in cancer therapy
- Polyamine Metabolism and Applications
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- RNA modifications and cancer
- PI3K/AKT/mTOR signaling in cancer
Guy's Hospital
2024
King's College London
2024
Ceinge Biotecnologie Avanzate (Italy)
2013-2023
University of Naples Federico II
2013-2023
Federico II University Hospital
2010-2020
Resistance to therapies that target homologous recombination deficiency (HRD) in breast cancer limits their overall effectiveness. Multiple, preclinically validated, mechanisms of resistance have been proposed, but existence and relative frequency clinical disease are unclear, as is how resistance.
Mutations in the MLH1 and MSH2 genes account for a majority of cases families with Lynch Syndrome. Germ-line mutations MSH6, PMS2 MLH3 are responsible disease minority cases, usually associated milder variable phenotypes. No germ-line MSH3 have so far been Syndrome, although it is known that impaired activity leads to partial defect mismatch repair (MMR), low levels microsatellite instability at loci dinucleotide repeats colorectal cancer (CRC), thus suggesting role carcinogenesis. To...
Epithelial‑to‑mesenchymal transition (EMT) confers stem cell‑like phenotype and more motile properties to carcinoma cells. During EMT, the expression of E‑cadherin decreases, resulting in loss cell‑cell adhesion increased migration. Expression Twist1 other pleiotropic transcription factors, such as Snail, is known activate EMT. We established primary colon cancer cell cultures from samples operated patients validated by cytogenetic molecular biology approaches. Western blot assay,...
Lynch syndrome is associated with germ-line mutations in the DNA mismatch repair (MMR) genes, mainly MLH1 and MSH2 . Most of reported these genes to date are point mutations, small deletions, insertions. Large genomic rearrangements MMR predisposing also occur, but frequency varies depending on population studied average from 5 20%. The aim this study was examine contribution large a well-characterised series 63 unrelated Southern Italian patients who were negative for pathogenic , MSH6...
Cellular plasticity, the ability of cells to switch from an epitheial phenotype a mesenchymal one and vice versa, plays crucial role in tumour progression metastases development. In 20-25% patients with colon cancer 18% rectal cancer, are present at time first diagnosis. They cause colorectal (CRC)-related mortality, defining stage IV CRC, which is characterized by relatively short overall survival. We previously isolated two primary adenocarcinoma cell cultures that had undergone...
Loss of function mismatch repair (MMR) genes, mainly MLH1 and MSH2, manifests as high levels microsatellite instability (MSI) that occurs in >90% carcinomas patients with Lynch syndrome (LS). The MSI‑high status has also been described sporadic colorectal cancer (CRC) associated BRAF gene mutation (V600E); this was not present LS‑associated cancers. study performed MSI analysis on 39 CRC selected according to Bethesda guidelines, V600E genotyping 26 cases classified or MSI‑low (15 MSI‑H 11...
Cowden syndrome (CS), Bannayan-Riley-Ruvalcaba (BRRS) and proteus are disorders known as PTEN hamartoma tumour (PHTS), that can show remarkable clinical overlap all caused by germline mutations. We here present two families, one affected CS the other BRRS, both carriers of specific pathogenetic missense mutation in exon 5 gene, within catalitic domain. Both PHTS families exhibited extremely variable phenotypes, showing inter- intra- familial variability. One characterised mutations, c.320A-...
Abstract: Lynch syndrome (LS), the most frequent form of hereditary colorectal cancer, involves mutations in mismatch repair genes. The aim this study was to identify MSH6 from 97 subjects negative for MLH1 and MSH2. By direct sequencing, we identified 27 variants, which, nine were novel. To verify pathogenicity these novel performed silico segregation analyses. Three variants predicted by analysis as damaging segregated with disease phenotype; while a frameshift deletion variant that yield...
Background: Lynch syndrome is associated with genetic variants in mismatch repair (MMR) genes. Pathogenic the MLH1 and MSH2 genes occur most families which phenotype highly penetrant. These testing criteria are likely to miss individuals due less penetrant MMR genes, such as MSH6, MLH3, MSH3, PMS2. So far, several mutations PMS2 gene have been described responsible for clinical manifestation of syndrome. Recent data reported that atypical were found primarily monoallelic gene. Methods: We...
Lynch Syndrome (LS) is associated with germline mutations in one of the mismatch repair (MMR) genes, including MutL homolog 1 (MLH1), MutS 2 (MSH2), MSH6, PMS1 2, system component (PMS2), MLH3 and MSH3. The identified MMR genes are point or large rearrangements. certainly pathogenetic whether they determine formation truncated protein. that arise splice sites classified as 'likely pathogenic' variants. In present study, a novel splicing mutation was identified, (named c.212‑1g>a), MSH2 gene....
Background: The loss or low expression of DNA mismatch repair (MMR) genes can result in genomic instability and tumorigenesis. One such gene, MSH2, is mutated rearranged Lynch syndrome (LS), which characterized by a high risk tumor development, including colorectal cancer. However, many variants identified this gene are often defined as uncertain significance (VUS). In study, we selected variant the 3′ untranslated region (UTR) MSH2 (c*226A > G), three affected members LS family already...
The molecular characterization of patients with Lynch syndrome (LS) involves germline testing to detect a deleterious mutation in one the genes mismatch repair (<em>MMR</em>) pathway. To date, however, large proportion clinical suspicion LS who undergo genetic do not show pathogenetic variant these genes. Germline DNA from 73 was examined next‑generation sequencing methods, using multigene custom panel designed and standardized by our research group, that targets set 15 Deleterious variants...
Background: Lynch syndrome, the most frequent form of hereditary colorectal cancer and involves mutations in mismatch repair genes. The aim this study was to identify MSH6 from 97 subjects negative for MLH1 MSH2. Methods: By direct sequencing, we identified 27 variants, which, nine were novel. To verify pathogenicity these novel variants performed silico segregation analyses. Results: Three predicted by analysis as damaging segregated with disease phenotype. While, a frameshift deletion...
Lynch syndrome is an autosomal dominant that can be subdivided into I, or site-specific colonic cancer, and II, extracolonic cancers, particularly carcinomas of the stomach, endometrium, biliary pancreatic systems, urinary tract. associated with point mutations large rearrangements in DNA MisMatch Repair (MMR) genes. This shows a variable phenotypic expression people who carry pathogenetic mutations. So far, correlation genotype-phenotype has not been definitely established. In this study,...
Mismatch Repair (MMR) gene dysregulation plays a fundamental role in Lynch Syndrome (LS) pathogenesis, form of hereditary colorectal cancer. Loss or overexpression key MMR genes leads to genome instability and tumorigenesis; however, the mechanisms controlling expression are unknown. One such gene, MSH2, exerts an important role, not only MMR, but also cell proliferation, apoptosis, cycle control. In this study, we explored functions underlying molecular increased MSH2 related c.*226A>G...
Familial adenomatous polyposis (FAP) is an autosomal dominant hereditary precancerous condition caused by germline pathogenetic variants in the tumor suppressor polyposis coli (<em>APC</em>) gene. Patients with FAP develop multiple gastrointestinal polyps usually at age of ~20 years, which, if untreated, become cancerous in 100% cases. Genotype‑phenotype associations have been extensively described; however, inter‑ and intra‑familial variability exists. It crucial to...
Early-onset or hereditary ovarian cancer is mostly associated with BRCA1 BRCA2 mutations. Mismatch repair genes sequence alteration frequently cause colorectal cancer, and, in less extent, other tumors, such as cancer. Subjects personal and/or family history suggestive for should be addressed to genetic counseling, aimed the identification, definition and management of syndrome, by a multidisciplinary approach.A woman very early onset epithelial underwent counseling testing. Pedigree...
Lynch syndrome (LS) is an autosomal dominant inherited disorder that primarily predisposes individuals to colorectal and endometrial cancer. It associated with pathogenic variants in DNA mismatch repair (MMR) genes. In this study, we report the case of a 16-year-old boy who developed precancerous colonic lesion had clinical suspicion LS. The proband was found have somatic MSI-H status. Analysis coding sequences flanking introns MLH1 MSH2 genes by Sanger sequencing led identification variant...
Colorectal cancer (CRC) is the second cause of deaths, with over 1 million new cases estimated every year. Familial adenomatous polyposis, MUTYH-associated polyposis and hamartomatous are inherited syndromes that account for 2%-5% all colon cancer. The mutated genes responsible vast majority these disorders, now known (MLH1, MSH2, MSH6, PMS2, APC, MYH, LKB1, SMAD4, BMPR1A, PTEN) specific mutations have been identified. Molecular caracterization CRCs allows pre-symptomatic diagnosis...