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In-depth mutational analyses of colorectal neuroendocrine carcinomas with adenoma or adenocarcinoma components.
- Source :
-
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc [Mod Pathol] 2017 Jan; Vol. 30 (1), pp. 95-103. Date of Electronic Publication: 2016 Sep 02. - Publication Year :
- 2017
-
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.
- Subjects :
- Adenocarcinoma pathology
Adenoma pathology
Adenomatous Polyposis Coli Protein genetics
Aged
Aged, 80 and over
Alleles
Carcinoma, Neuroendocrine pathology
Colorectal Neoplasms pathology
DNA Mutational Analysis
Female
Gene Frequency
Humans
Male
Middle Aged
Mutation
Proto-Oncogene Proteins p21(ras) genetics
Tumor Suppressor Protein p53 genetics
Exome Sequencing
Adenocarcinoma genetics
Adenoma genetics
Carcinoma, Neuroendocrine genetics
Colorectal Neoplasms genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1530-0285
- Volume :
- 30
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
- Publication Type :
- Academic Journal
- Accession number :
- 27586204
- Full Text :
- https://doi.org/10.1038/modpathol.2016.150