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dc.contributor.authorMamlouk, S.
dc.contributor.authorSimon, T.
dc.contributor.authorTomás, L.
dc.contributor.authorWedge, David C
dc.contributor.authorArnold, A.
dc.contributor.authorMenne, A.
dc.contributor.authorHorst, D.
dc.contributor.authorCapper, D.
dc.contributor.authorMorkel, M.
dc.contributor.authorPosada, D.
dc.contributor.authorSers, C.
dc.contributor.authorBläker, H.
dc.date.accessioned2020-10-06T13:33:49Z
dc.date.available2020-10-06T13:33:49Z
dc.date.issued2020en
dc.identifier.citationMamlouk S, Simon T, Tomas L, Wedge DC, Arnold A, Menne A, et al. Malignant transformation and genetic alterations are uncoupled in early colorectal cancer progression. BMC Biol. 2020;18(1):116.en
dc.identifier.pmid32895052en
dc.identifier.doi10.1186/s12915-020-00844-xen
dc.identifier.urihttp://hdl.handle.net/10541/623345
dc.description.abstractBackground: Colorectal cancer (CRC) development is generally accepted as a sequential process, with genetic mutations determining phenotypic tumor progression. However, matching genetic profiles with histological transition requires the analyses of temporal samples from the same patient at key stages of progression. Results: Here, we compared the genetic profiles of 34 early carcinomas with their respective adenomatous precursors to assess timing and heterogeneity of driver alterations accompanying the switch from benign adenoma to malignant carcinoma. In almost half of the cases, driver mutations specific to the carcinoma stage were not observed. In samples where carcinoma-specific alterations were present, TP53 mutations and chromosome 20 copy gains commonly accompanied the switch from adenomatous tissue to carcinoma. Remarkably, 40% and 50% of high-grade adenomas shared TP53 mutations and chromosome 20 gains, respectively, with their matched carcinomas. In addition, multi-regional analyses revealed greater heterogeneity of driver mutations in adenomas compared to their matched carcinomas. Conclusion: Genetic alterations in TP53 and chromosome 20 occur at the earliest histological stage in colorectal carcinomas (pTis and pT1). However, high-grade adenomas can share these alterations despite their histological distinction. Based on the well-defined sequence of CRC development, we suggest that the timing of genetic changes during neoplastic progression is frequently uncoupled from histological progression.en
dc.language.isoenen
dc.relation.urlhttps://dx.doi.org/10.1186/s12915-020-00844-xen
dc.titleMalignant transformation and genetic alterations are uncoupled in early colorectal cancer progressionen
dc.typeArticleen
dc.contributor.departmentInstitute of Pathology, Charité Universitätsmedizin Berlin, Berlin, Germany. soulafa.mamlouk@charite.de.en
dc.identifier.journalBMC Biologyen
dc.description.noteen]
refterms.dateFOA2020-10-12T09:33:09Z


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