cad a22 4500 551468351 20200124035232.0 cr unu---uuuuu 181215e20181106xx s 000 0 eng 10.5167/uzh-159450 doi 10.1080/15592294.2018.1543504 doi (ZORA)oai:www.zora.uzh.ch:159450 610 ddc 30398409 pmid The proto CpG island methylator phenotype of sessile serrated adenomas/polyps [Elektronische Daten] [Hannah R Parker, Stephany Orjuela, Andreia Martinho Oliveira, Fabrizio Cereatti, Matthias Sauter, Henriette Heinrich, Giulia Tanzi, Achim Weber, Paul Komminoth, Stephan Vavricka, Luca Albanese, Federico Buffoli, Mark D Robinson, Giancarlo Marra] openAccess eu-repo Sessile serrated adenomas/polyps (SSA/Ps) are the putative precursors of the ~20% of colon cancers with the CpG island methylator phenotype (CIMP). To investigate the epigenetic phenotype of these precancers, we prospectively collected fresh-tissue samples of 17 SSA/Ps and 15 conventional adenomas (cADNs), each with a matched sample of normal mucosa. Their DNA was subjected to bisulfite next-generation sequencing to assess methylation levels at ~2.7 million CpGs located predominantly in gene regulatory regions and spanning 80.5Mb; RNA was sequenced to define the samples' transcriptomes. Compared with normal mucosa, SSA/Ps and cADNs exhibited markedly remodeled methylomes. In cADNs, hypomethylated regions were far more numerous (18,417 vs 4288 in SSA/Ps) and rarely affected CpG islands/shores. SSA/Ps seemed to have escaped this wave of demethylation. Cytosine hypermethylation in SSA/Ps was more pervasive (hypermethylated regions: 22,147 vs 15,965 in cADNs; hypermethylated genes: 4938 vs 3443 in cADNs) and more extensive (region for region), and it occurred mainly within CpG islands and shores. Given its resemblance to the CIMP typical of SSA/Ps' putative descendant colon cancers, we refer to the SSA/P methylation phenotype as proto-CIMP. Verification studies of six hypermethylated regions in an independent series of precancers demonstrated DNA methylation markers' high potential for predicting the diagnosis of SSA/Ps and cADNs. Surprisingly, proto-CIMP in SSA/Ps was associated with upregulated gene expression; downregulation was more common in cADNs. In conclusion, the epigenetic landscape of SSA/Ps differs markedly from that of cADNs. These differences are a potentially rich source of novel tissue-based and noninvasive biomarkers. Institute of Pathology and Molecular Pathology zora Institute of Molecular Life Sciences zora Parker Hannah R. joint author Orjuela Stephany joint author Martinho Oliveira Andreia joint author Cereatti Fabrizio joint author Sauter Matthias joint author Heinrich Henriette joint author Tanzi Giulia joint author Weber Achim joint author Komminoth Paul joint author Vavricka Stephan joint author Albanese Luca joint author Buffoli Federico joint author Robinson Mark D. joint author Marra Giancarlo joint author Epigenetics 13(10/11):1088-1105 https://www.zora.uzh.ch/id/eprint/159450/1/Parker_epigenetics_2018.pdf text/html WWW-Backlink auf das Repository 1 Journal Article PeerReviewed zora ZORA 856 40 https://www.zora.uzh.ch/id/eprint/159450/1/Parker_epigenetics_2018.pdf text/html WWW-Backlink auf das Repository ZORA 700 1- Parker Hannah R. joint author ZORA 700 1- Orjuela Stephany joint author ZORA 700 1- Martinho Oliveira Andreia joint author ZORA 700 1- Cereatti Fabrizio joint author ZORA 700 1- Sauter Matthias joint author ZORA 700 1- Heinrich Henriette joint author ZORA 700 1- Tanzi Giulia joint author ZORA 700 1- Weber Achim joint author ZORA 700 1- Komminoth Paul joint author ZORA 700 1- Vavricka Stephan joint author ZORA 700 1- Albanese Luca joint author ZORA 700 1- Buffoli Federico joint author ZORA 700 1- Robinson Mark D. joint author ZORA 700 1- Marra Giancarlo joint author ZORA 773 0- Epigenetics 13(10/11):1088-1105 BK010053 XK010053 XK010000 ZORA ZORA ZORA Journal Article openAccess