Project description:Transcriptional profiling of early-onset sporadic rectal adenocarcinoma, comparing Wnt- and Wnt+ rectal tumor. Goal was to determine differentially expressed genes between them based on global gene expression.
Project description:Copy number profiling of early-onset sporadic rectal adenocarcinoma, comparing Wnt- and Wnt+ rectal tumor. Goal was to determine differentially altered genes between them based on global copy no.
Project description:Overall declines in incidence of rectal cancer (RC) in patients older than 50 years have been mostly attributed to improvement in treatment modalities and introduction of age-based screening. Recent studies, however, have shown a rise in the incidence of RC in patients younger than 50 years. The etiology of early-onset (EO) RC is not well understood. The aim of this study is to elucidate the molecular features of (EO) RC and show its uniqueness compared to late-onset (LO) disease.Two cohorts of patients with sporadic RC were identified. Tumors and matching non-involved tissues from six (EO) RC patients (< 50 years) and six (LO) RC patients (>65 years) were obtained from Pathology archives. Deparaffinized tissues were macro-dissected from FFPE sections, RNA isolated and used for expression profiling of 770 cancer related genes representing 13 canonical pathways. Statistical analysis was performed using the Gene Expression R-script module within the nCounter software v2.6. A gene was considered to be above background if the average count for the target gene was greater than the average counts for the eight negative control genes and if the P value of the t-test was less than 0.05.When we compared rectal tumors to non-involved rectal tissues, changes in expression levels of 171 genes were statistically significant in early-onset group and 151 genes in late-onset group. Further comparative gene expression analysis between early- and late-onset rectal tumors normalized to their matching non-involved tissues revealed that changes in expression of 65 genes were unique to early-onset rectal tumors with 16 genes being up- and 49 genes down-regulated using the cutoff criteria of expression levels difference >2 fold and p-value <0.01. At the pathway level, MAPK signaling was the most deregulated pathway in early-onset rectal tumors compared to PI3K-AKT signaling pathway being the most deregulated in late-onset rectal tumors.Results of this study suggest that sporadic early-onset rectal cancer is characterized by distinct molecular events compared to late-onset disease.
Project description:Gene fusions (GFs) represent a distinct class of structural variants identified consistently in cancer genomes across multiple cancer types. Several GFs exhibit gain of oncogenic function, and thus, have been the focus for development of efficient targeted therapies. Here, we present a comprehensive landscape of GFs in early-onset sporadic rectal cancer (EOSRC), a poorly studied colorectal cancer (CRC) subtype prevalent in developing countries from the transcriptome analysis of 37 EOSRC samples. Gene Ontology analysis revealed enrichment of unique biological process terms associated with 5’- and 3’- fusion partner genes. An extensive network analysis highlighted several promiscuous genes participating in GF formation. Further, an in-depth evaluation revealed significant association of these promiscuous genes with chromosome fragile sites.
Project description:Colorectal cancer is the third most common cancer diagnosed worldwide. Although epidemiology data show a marked variability around the world, its overall incidence rate shows a slow but steady decrease, mainly in developed countries. Conversely, early-onset colorectal cancer appears to display an opposite trend with an overall prevalence in United States and European Union ranging from 3.0% and 8.6%. Colorectal cancer has a substantial proportion of familial cases. In particular, early age at onset is especially suggestive of hereditary predisposition. The clinicopathological and molecular features of colorectal cancer cases show a marked heterogeneity not only between early- and late-onset cases but also within the early-onset group. Two distinct subtypes of early-onset colorectal cancers can be identified: a "sporadic" subtype, usually without family history, and an inherited subtype arising in the context of well defined hereditary syndromes. The pathogenesis of the early-onset disease is substantially well characterized in the inherited subtype, which is mainly associated to the Lynch syndrome and occasionally to other rare mendelian diseases, whereas in the "sporadic" subtype the origin of the disease may be attributed to the presence of various common/rare genetic variants, so far largely unidentified, displaying variable penetrance. These variants are thought to act cumulatively to increase the risk of colorectal cancer, and presumably to also anticipate its onset. Efforts are ongoing in the attempt to unravel the intricate genetic basis of this "sporadic" early-onset disease. A better knowledge of molecular entities and pathways may impact on family-tailored prevention and clinical management strategies.