Abstract
The genetic background is unknown for the 50-60% of the HNPCC families, who fulfill the Amsterdam criteria, but do not have a mutation in an MMR gene, and is referred to as FCCTX. This study reviews the clinical, morphological and molecular characteristics of FCCTX, and discusses the molecular genetic methods used to localize new FCCTX genes, along with an overview of the genes and chromosomal areas that possibly relate to FCCTX. FCCTX is a heterogeneous group, mainly comprising cases caused by single high-penetrance genes, or by multiple low-penetrance genes acting together, and sporadic CRC cases. FCCTX differs in clinical, morphological and molecular genetic characteristics compared to LS, including a later age of onset, distal location of tumours in the colon, lower risk of developing extracolonic tumours and a higher adenoma/carcinoma ratio, which indicates a slower progression to CRC. Certain characteristics are shared with sporadic CRC, e.g. similarities in gene expression and a high degree of CIN+, with significanly increased 20q gain in FCCTX. Other molecular characteristics of FCCTX include longer telomere length and hypomethylation of LINE-1, both being a possible explanation for CIN+. Some genes in FCCTX families (RPS20, BMPR1A, SEMA4A) have been identified by using a combination of linkage analysis and sequencing. Sequencing strategies and subsequent bioinformatics are improving fast. Exome sequencing and whole genome sequencing are currently the most promising tools. Finally, the involvement of CNV’s and regulatory sequences are widely unexplored and would be interesting for further investigation in FCCTX.
Keywords: Amsterdam positive, Colorectal cancer, Familial cancer, FCCTX, HNPCC, Microsatellite stable, MMR negative.
Current Genomics
Title:Familial Colorectal Cancer Type X
Volume: 18 Issue: 4
Author(s): Diana Bregner Zetner and Marie Luise Bisgaard*
Affiliation:
- Department of Cellular and Molecular Medicine, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3C, DK-2200 Copenhagen N,Denmark
Keywords: Amsterdam positive, Colorectal cancer, Familial cancer, FCCTX, HNPCC, Microsatellite stable, MMR negative.
Abstract: The genetic background is unknown for the 50-60% of the HNPCC families, who fulfill the Amsterdam criteria, but do not have a mutation in an MMR gene, and is referred to as FCCTX. This study reviews the clinical, morphological and molecular characteristics of FCCTX, and discusses the molecular genetic methods used to localize new FCCTX genes, along with an overview of the genes and chromosomal areas that possibly relate to FCCTX. FCCTX is a heterogeneous group, mainly comprising cases caused by single high-penetrance genes, or by multiple low-penetrance genes acting together, and sporadic CRC cases. FCCTX differs in clinical, morphological and molecular genetic characteristics compared to LS, including a later age of onset, distal location of tumours in the colon, lower risk of developing extracolonic tumours and a higher adenoma/carcinoma ratio, which indicates a slower progression to CRC. Certain characteristics are shared with sporadic CRC, e.g. similarities in gene expression and a high degree of CIN+, with significanly increased 20q gain in FCCTX. Other molecular characteristics of FCCTX include longer telomere length and hypomethylation of LINE-1, both being a possible explanation for CIN+. Some genes in FCCTX families (RPS20, BMPR1A, SEMA4A) have been identified by using a combination of linkage analysis and sequencing. Sequencing strategies and subsequent bioinformatics are improving fast. Exome sequencing and whole genome sequencing are currently the most promising tools. Finally, the involvement of CNV’s and regulatory sequences are widely unexplored and would be interesting for further investigation in FCCTX.
Export Options
About this article
Cite this article as:
Zetner Bregner Diana and Bisgaard Luise Marie*, Familial Colorectal Cancer Type X, Current Genomics 2017; 18 (4) . https://dx.doi.org/10.2174/1389202918666170307161643
DOI https://dx.doi.org/10.2174/1389202918666170307161643 |
Print ISSN 1389-2029 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5488 |
Call for Papers in Thematic Issues
Advanced AI Techniques in Big Genomic Data Analysis
The thematic issue on "Advanced AI Techniques in Big Genomic Data Analysis" aims to explore the cutting-edge methodologies and applications of artificial intelligence (AI) in the realm of genomic research, where vast amounts of data pose both challenges and opportunities. This issue will cover a broad spectrum of AI-driven strategies, ...read more
Advanced Computational Algorithms and Artificial Intelligence in Clinical Pharmacogenomics
In the era of personalized medicine, understanding the relationship between genetics and drug response is crucial. This issue delves into innovative methodologies, leveraging deep computational analysis and artificial intelligence, to enhance the field of Clinical Pharmacogenomics. The interdisciplinary approach harnesses the power of advanced high-throughput genotyping technologies, sophisticated computational analysis, ...read more
Applications of Single-cell Sequencing Technology in Reproductive Medicine
Single cell sequencing (SCS) technology utilizes individual cells' genetic material to sequence their genome, transcriptome, and epigenetics at the molecular level. It offers insights into cell heterogeneity and enables the study of limited biological materials. Since its recognition as a valuable technique in 2011, single cell sequencing has yielded numerous ...read more
Big Data in Cancer Research
Cancer is a significant threat to human life and health, remaining a highly aggressive killer. It is a leading cause of death worldwide and represents a crucial medical issue for humanity. However, in the past decade, the effectiveness of new synthetic anticancer agents has not matched the current clinical speculation. ...read more
Related Journals
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
QSAR Multi-Target in Drug Discovery: A Review
Current Computer-Aided Drug Design Cell Hierarchy, Metabolic Flexibility and Systems Approaches to Cancer Treatment
Current Pharmaceutical Biotechnology Micro-RNA in Disease and Gene Therapy
Current Drug Discovery Technologies Detection of Melatonin Production from the Intestinal Epithelium Using Electrochemical Methods
Current Pharmaceutical Design Optimizing Tumor-Reactive γδT Cells for Antibody-Based Cancer Immunotherapy
Current Molecular Medicine Gene Expression-Based Pharmacodynamic Biomarkers: The Beginning of a New Era in Biomarker-Driven Anti-Tumor Drug Development
Current Molecular Medicine Metals and Metal Derivatives in Medicine
Mini-Reviews in Medicinal Chemistry Activation of Intrinsic Apoptosis and G1 Cell Cycle Arrest by a Triazole Precursor, N-(4-chlorophenyl)-2-(4-(3,4,5-trimethoxybenzyloxy)benzoyl)-hydrazinecarbothioamide in Breast Cancer Cell Line
Anti-Cancer Agents in Medicinal Chemistry Anti-Angiogenic Peptides for Cancer Therapeutics
Current Pharmaceutical Biotechnology Liposomes: An Emerging Approach for the Treatment of Cancer
Current Pharmaceutical Design EDITORIAL (Thematic Issue: Special Thematic Issuue: Development of Biomarkers in Tumors of Digestive System Part I)
Anti-Cancer Agents in Medicinal Chemistry MicroRNA-34a and its target genes: Key factors in cancer multidrug resistance
Current Pharmaceutical Design Heterologous Expression and Characterization of Flavinadenine Dinucleotide Synthetase from <i>Candida famata</i> for Flavin Adenine Dinucleotide Production
Protein & Peptide Letters Engineered Peptides for Applications in Cancer-Targeted Drug Delivery and Tumor Detection
Mini-Reviews in Medicinal Chemistry Killing Glioma ‘Stem-like’ Cells via Drug-Induced Relocation of Endosomal Urokinase Proteins
Anti-Cancer Agents in Medicinal Chemistry Four-Component Synthesis of 1,2-Dihydropyridine Derivatives and their Evaluation as Anticancer Agents
Medicinal Chemistry Structure and Mechanism of Arylamine N-Acetyltransferases
Current Topics in Medicinal Chemistry Therapeutic Potential of Targeting Transforming Growth Factor-beta in Colorectal Cancer: Rational and Progress
Current Pharmaceutical Design Targeted Delivery of Cabazitaxel by Conjugation to Albumin-PEG-folate Nanoparticles Using a Cysteine-acrylate Linker and Simple Synthesis Conditions
Current Drug Delivery Tumor-Targeting Peptides and Small Molecules as Anti-Cancer Agents to Overcome Drug Resistance
Current Medicinal Chemistry