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    Malignant transformation and genetic alterations are uncoupled in early colorectal cancer progression

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    Authors
    Mamlouk, S.
    Simon, T.
    Tomás, L.
    Wedge, David C
    Arnold, A.
    Menne, A.
    Horst, D.
    Capper, D.
    Morkel, M.
    Posada, D.
    Sers, C.
    Bläker, H.
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    Affiliation
    Institute of Pathology, Charité Universitätsmedizin Berlin, Berlin, Germany. soulafa.mamlouk@charite.de.
    Issue Date
    2020
    
    Metadata
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    Abstract
    Background: 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.
    Citation
    Mamlouk 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.
    Journal
    BMC Biology
    URI
    http://hdl.handle.net/10541/623345
    DOI
    10.1186/s12915-020-00844-x
    PubMed ID
    32895052
    Additional Links
    https://dx.doi.org/10.1186/s12915-020-00844-x
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1186/s12915-020-00844-x
    Scopus Count
    Collections
    All Paterson Institute for Cancer Research

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