Unknown

Dataset Information

0

Distinct gene expression signatures in lynch syndrome and familial colorectal cancer type x.


ABSTRACT: Heredity is estimated to cause at least 20% of colorectal cancer. The hereditary nonpolyposis colorectal cancer subset is divided into Lynch syndrome and familial colorectal cancer type X (FCCTX) based on presence of mismatch repair (MMR) gene defects.We addressed the gene expression signatures in colorectal cancer linked to Lynch syndrome and FCCTX with the aim to identify candidate genes and to map signaling pathways relevant in hereditary colorectal carcinogenesis.The 18 k whole-genome c-DNA-mediated annealing, selection, extension, and ligation (WG-DASL) assay was applied to 123 colorectal cancers, including 39 Lynch syndrome tumors and 37 FCCTX tumors. Target genes were technically validated using real-time quantitative RT-PCR (qRT-PCR) and the expression signature was validated in independent datasets.Colorectal cancers linked to Lynch syndrome and FCCTX showed distinct gene expression profiles, which by significance analysis of microarrays (SAM) differed by 2188 genes. Functional pathways involved were related to G-protein coupled receptor signaling, oxidative phosphorylation, and cell cycle function and mitosis. qRT-PCR verified altered expression of the selected genes NDUFA9, AXIN2, MYC, DNA2 and H2AFZ. Application of the 2188-gene signature to independent datasets showed strong correlation to MMR status.Distinct genetic profiles and deregulation of different canonical pathways apply to Lynch syndrome and FCCTX and key targets herein may be relevant to pursue for refined diagnostic and therapeutic strategies in hereditary colorectal cancer.

SUBMITTER: Dominguez-Valentin M 

PROVIDER: S-EPMC3741139 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

altmetric image

Publications

Distinct gene expression signatures in lynch syndrome and familial colorectal cancer type x.

Dominguez-Valentin Mev M   Therkildsen Christina C   Veerla Srinivas S   Jönsson Mats M   Bernstein Inge I   Borg Ake A   Nilbert Mef M  

PloS one 20130812 8


<h4>Introduction</h4>Heredity is estimated to cause at least 20% of colorectal cancer. The hereditary nonpolyposis colorectal cancer subset is divided into Lynch syndrome and familial colorectal cancer type X (FCCTX) based on presence of mismatch repair (MMR) gene defects.<h4>Purpose</h4>We addressed the gene expression signatures in colorectal cancer linked to Lynch syndrome and FCCTX with the aim to identify candidate genes and to map signaling pathways relevant in hereditary colorectal carcin  ...[more]

Similar Datasets

| S-EPMC4119982 | biostudies-literature
| S-EPMC7245918 | biostudies-literature
| S-EPMC7514801 | biostudies-literature
| S-EPMC5559789 | biostudies-other
| S-EPMC4231285 | biostudies-literature
| S-EPMC3859667 | biostudies-literature
| S-EPMC7493642 | biostudies-literature
| S-EPMC2964436 | biostudies-literature
2012-06-01 | E-GEOD-38405 | biostudies-arrayexpress
2012-06-02 | GSE38405 | GEO