GRCh38 · COSMIC v99

Summary

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Reference
In-depth mutational analyses of colorectal neuroendocrine carcinomas with adenoma or adenocarcinoma components.
Paper ID
COSP42149
Authors
Woischke C, Schaaf CW, Yang HM, Vieth M, Veits L, Geddert H, Märkl B, Stömmer P, Schaeffer DF, Frölich M, Blum H, Vosberg S, Greif PA, Jung A, Kirchner T and Horst D
Affiliation
Pathologisches Institut der Ludwig-Maximilians-Universität (LMU), München, Germany.
Journal
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 2016
ISSN: 1530-0285
PMID: 27586204 (view at PubMed or Europe PMC)
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.Modern Pathology advance online publication, 2 September 2016; doi:10.1038/modpathol.2016.150.
Paper Status
Curated