Project description:<p>Lynch Syndrome (LS) tumors are characterized by constitutional mutations in DNA mismatch-repair genes. Colorectal cancers (CRCs) are the predominant tumor type in patients with LS. Here, we have used whole-genome and transcriptome sequencing of LS- CRC to find similarities and differences of mutation and gene expression characteristics between LS-CRC and sporadic CRC (data provided by <a href="./study.cgi?study_id=phs000178">TCGA via dbGaP</a>). Furthermore, we were interested in the molecular heterogeneity of LS-CRC. We have performed a molecular characterization of LS-tumors and of matched tumor-distant reference colonic mucosa based on whole-genome DNA- and RNA-sequencing analyses. Our data indicates the existence of two subgroups of LS-CRCs, G1 and G2, where G1 tumors show a higher number of somatic mutations, higher microsatellite slippage and a different mutation spectrum.</p>
Project description:We aimed to provide a molecular description of Lynch syndrome-associated urothelial cancer in relation to molecular subtypes of sporadic bladder cancer. Whole genome mRNA expression profiles of 41 tumors and immunohistochemical stainings against FGFR3, KRT5, CCNB1, RB1, and CDKN2A (p16) of 37 tumors from Lynch syndrome patients were generated. Pathological data, microsatellite instability, anatomic location, and overall survival data was analyzed and compared with data from sporadic bladder cancer.
Project description:In patients diagnosed as endometrial cancer by thorough pathologic examinations, Lynch syndromes are screened by (1)immunohistochemical staining (for MLH1, MSH2, MSH6 and PMS2), (2) tests of microsatellite instability and (3) clinical criteria (Amsterdam I or II criteria and Bethesda criteria). For patients with any suspicious discoveries of Lynch syndromes from aforementioned screening methods, a molecular diagnosis with next-generation sequencing for mismatch repair genes (MLH1, MSH2, MSH6, PMS2, and EPCAM) is given to confirm Lynch syndromes. For patients of Lynch syndromes and endometrial cancer, relatives of blood lineage are tested by Sanger method or qPCR to find out carriers of mutation genes of Lynch syndromes.
Project description:Molecular characterization of 20 tumors of 18 children with Lynch syndrome to investigate causality. This characterization includes the investigation of second hits, tumor mutational load, mutational signatures and MMR protein expression.
Project description:A clinically applicably strategy for molecular screening for Lynch Syndrome is being implemented in Denmark.
Based on sequential analysis with immunohistochemistry and methylation analysis, patients with possible hereditary colorectal cancer are identified. These patients are offered genetic risk assessment and counselling.
The study hypothesis is that molecular screening will identify more patients with Lynch Syndrome than the family history alone.
Prospective data collection is performed using established clinical databases.