Project description:We compared the transcriptional profiles of colon tissues and patient derived organoids (PDOs) in genetic polyposis syndromes (FAP, LYNCH, JPS, and PJS)
Project description:RNA sequencing analysis of small RNA expression in sessile serrated adenoma/polyps, hyperplastic polyps, adenomatous polyps, uninvolved colon and control colon
Project description:In this study we compared gene expression of precancerous SSA/Ps and benign MVHPs with particular focus on genes involved in colorectal cancer. We also identify genes whose expression can be used to differentiate SSA/Ps and MVHPs. These results provide insight into the development of SSA/Ps and illustrates differences between these related colonic polyps. Total RNA from 6 samples of normal colon, 6 microvesicular hyperplastic polyps, and 6 sessile serrated adenomas/polyps were compared
Project description:Colon polyps represent precursor lesions of colon cancers and their malignant potential varies according to histological subtype. A rare subtype of colon polyps is the Peutz-Jeghers (PJ) polyp. PJ polyps mostly occur in the context of Peutz-Jeghers Syndrome which is characterized by the development of multiple polyps in the intestinal tract and hyperpigmentation of oral mucosa and lips. Peutz-Jeghers Syndrome is an autosomal dominant disorder caused by germline mutations of the Serine Threonin Kinase STK11 (LKB1). PJ polyps very rarely occur outside of Peutz-Jeghers Syndrome and are then referred to as solitary PJ polyps. Contrary to Peutz-Jeghers Syndrome, the genetic basis and the malignant potential of solitary PJ polyps is currently unknown. To date, only one study described a sporadic PJ polyp finding no mutations of STK11, indicating that the molecular profile of solitary PJ polyps differs from Peutz-Jeghers syndrome. Methylome analysis revealed global hypomethylation and CpG island hypermethylation, two features that have been described as hallmarks of the colorectal cancer epigenome. These results provide a paradigm for a premalignant lesion that is defined by epigenetic changes.
Project description:Details of the series are available in the publication Cardoso J. et al., “Chromosomal instability in MYH- and APC-mutant adenomatous polyps”, Cancer Research, accepted for publication. Abstract of the publication: “The vast majority of colorectal cancers display genetic instability, either in the chromosomal (CIN) or microsatellite (MIN) forms. While CIN tumors are per definition aneuploid, MIN colorectal cancers, caused by loss of mismatch repair function, are usually near-diploid. Recently, bi-allelic germline mutations in the MYH gene, were found to be responsible for MAP (MYH associated polyposis), an autosomal recessive predisposition to multiple colorectal polyps, often indistinguishable from the dominant FAP (familial adenomatous polyposis) syndrome caused by inherited APC mutations. Here, we analyzed MYH- and APC-mutant polyps by combining laser-capture microdissection, isothermal genomic DNA amplification, and array-CGH (comparative genomic hybridization). Smoothed quantile regression methods were applied to the MAP and FAP genomic profiles to discriminate chromosomes predominantly affected by gains and losses. Up to 80% of the MAP polyps showed aneuploid changes, which is significantly higher than the 60% found among FAP polyps. Both MAP and FAP adenomas were characterized by frequent losses at chromosome 1p, 17, 19 and 22, and gains affecting chromosome 7 and 13. The observation that aneuploidy is already detectable at early stages of MYH-driven tumorigenesis raises the possibility that CIN may contribute significantly to accelerated tumor progression, increased cancer risk, and poor prognosis in MAP.” Keywords: repeat, BAC, CGH
