Ola Nilsson1. 1. Sahlgrenska Cancer Center, Institute of Biomedicine, Sahlgrenska Academy at the University of Gothenburg, Göteborg, Sweden. ola.nilsson@llcr.med.gu.se
Abstract
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.
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.
Authors: Ilda Patrícia Ribeiro; Francisco Marques; Francisco Caramelo; João Pereira; Miguel Patrício; Hugo Prazeres; José Ferrão; Maria José Julião; Miguel Castelo-Branco; Joana Barbosa de Melo; Isabel Poiares Baptista; Isabel Marques Carreira Journal: Cell Oncol (Dordr) Date: 2013-12-19 Impact factor: 6.730