In-depth mutational analyses of colorectal neuroendocrine carcinomas with adenoma or adenocarcinoma components
| Autor: | Bruno Märkl, Andreas Jung, David F. Schaeffer, Helmut Blum, Hui-Min Yang, Michael Vieth, Matthias Frölich, Christian Schaaf, David Horst, Helene Geddert, Christine Woischke, Lothar Veits, Philipp A. Greif, Peter E. Stömmer, Thomas Kirchner, Sebastian Vosberg |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Adenoma
Male 0301 basic medicine Pathology medicine.medical_specialty Adenomatous Polyposis Coli Protein DNA Mutational Analysis Adenocarcinoma Biology medicine.disease_cause Pathology and Forensic Medicine Malignant transformation Proto-Oncogene Proteins p21(ras) Surgical pathology 03 medical and health sciences 0302 clinical medicine Gene Frequency Exome Sequencing medicine Humans Allele frequency Alleles Aged Aged 80 and over Cytogenetics Middle Aged medicine.disease digestive system diseases Carcinoma Neuroendocrine 030104 developmental biology 030220 oncology & carcinogenesis Mutation Female KRAS Tumor Suppressor Protein p53 Colorectal Neoplasms Hematopathology |
| Zdroj: | Modern Pathology. 30:95-103 |
| ISSN: | 0893-3952 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink