In-depth mutational analyses of colorectal neuroendocrine carcinomas with adenoma or adenocarcinoma components View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-01

AUTHORS

Christine Woischke, Christian W Schaaf, Hui-Min Yang, Michael Vieth, Lothar Veits, Helene Geddert, Bruno Märkl, Peter Stömmer, David F Schaeffer, Matthias Frölich, Helmut Blum, Sebastian Vosberg, Philipp A Greif, Andreas Jung, Thomas Kirchner, David Horst

ABSTRACT

Neuroendocrine carcinomas (NECs) of the colorectum are rare but highly aggressive neoplasms. These tumors show some shared genetic alterations with colorectal adenocarcinomas, and most of them have adjacent glandular adenoma or adenocarcinoma components. However, genetic data on colorectal NECs still are sparse and insufficient for definite conclusions regarding their molecular origin. Based on morphological characterization, panel and whole-exome sequencing, we here present results from an in-depth analysis of a collection of 15 colorectal NECs with glandular components, 10 of which by definition were mixed adenoneuroendocrine carcinomas (MANECs). Among shared genetic alterations of both tumor components, we most frequently found TP53, KRAS and APC mutations that also had highest allele frequencies. Mutations exclusive to glandular or neuroendocrine components outnumbered shared mutations but occurred at lower allele frequencies. Our findings not only provide additional evidence for a common clonal origin of colorectal NECs and adjacent glandular tumor components, but strongly suggest their development through the classical adenoma-carcinoma sequence. Moreover, our data imply early separation of glandular and neuroendocrine components during malignant transformation with subsequent independent mutational evolution. More... »

PAGES

95-103

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/modpathol.2016.150

DOI

http://dx.doi.org/10.1038/modpathol.2016.150

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1022493987

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/27586204


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