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Colorectal Cancer Cell Surface Protein Profiling Using an Antibody Microarray and Fluorescence Multiplexing
Published on: September 25, 2011
Profiling of ileal carcinoids
1Sahlgrenska Cancer Center, Institute of Biomedicine, Sahlgrenska Academy at the University of Gothenburg, Göteborg, Sweden. ola.nilsson@llcr.med.gu.se
Unlabelled:
Identification of common molecular mechanisms is needed to facilitate the development of new treatment options for patients with ileal carcinoids.
Purpose Of Review:
Recent profiling studies on ileal carcinoids were examined to obtain a comprehensive view of risk factors, genetic aberrations, and transcriptional alterations. Special attention was paid to mechanisms that could provide novel targets for therapy.
Results:
Genome-wide association studies have shown that single nucleotide polymorphisms (SNPs) at IL12A and DAD1 are associated with an increased risk of ileal carcinoids. Genomic profiling revealed distinct patterns of copy-number alterations in ileal carcinoids. Two groups of carcinoids could be identified by hierarchical clustering. A major group of tumors was characterized by loss on chromosome 18 followed by additional losses on chromosomes 3p, 11q, and 13. Three minimal common regions of deletions were identified at 18q21.1-q21.31, 18q22.1-q22.2, and 18q22.3-q23. A minor group of tumors was characterized by clustered gains on chromosomes 4, 5, 7, 14, and 20. Expression profiling identified three groups of ileal carcinoids by principal component analysis. Tumor progression was associated with changes in gene expression including downregulation of MIR133A. Candidate genes for targeted therapy included ERBB2/HER2, DAD1, PRKCA, RYBP, CASP1, CASP4, CASP5, VMAT1, RET, APLP1, OR51E1, GPR112, SPOCK1, RUNX1, and MIR133A.
Conclusion:
Profiling of ileal carcinoids has revealed recurrent genetic alterations and distinct patterns of gene expression. Frequent alterations in cellular pathways and genes were identified, suggesting novel targets for therapy. Translational studies are needed to validate suggested molecular targets.
Insights
Profiling ileal carcinoids reveals genetic alterations and gene expression patterns. These findings suggest novel therapeutic targets for ileal carcinoid tumors, requiring further translational studies for validation.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Ileal carcinoids require new treatment options.
- Understanding molecular mechanisms is crucial for developing targeted therapies.
Purpose of the Study:
- To comprehensively review risk factors, genetic aberrations, and transcriptional alterations in ileal carcinoids.
- To identify novel therapeutic targets by analyzing molecular mechanisms.
Main Methods:
- Examined recent profiling studies on ileal carcinoids.
- Utilized genome-wide association studies (GWAS) and genomic/expression profiling.
- Applied hierarchical clustering and principal component analysis (PCA).
Main Results:
- Identified single nucleotide polymorphisms (SNPs) in IL12A and DAD1 associated with increased risk.
- Revealed distinct copy-number alteration patterns, classifying tumors into two groups based on chromosomal losses (e.g., chromosome 18).
- Expression profiling identified three groups, with MIR133A downregulation linked to tumor progression. Candidate therapeutic targets include ERBB2/HER2, DAD1, and MIR133A.
Conclusions:
- Ileal carcinoid profiling identified recurrent genetic alterations and distinct gene expression patterns.
- Frequent alterations in cellular pathways and genes suggest novel therapeutic targets.
- Translational studies are necessary to validate the identified molecular targets.
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