Dataset Information

Ena-DATASET-MUG-29-10-2013-10:52:10:827-14 - samples

ABSTRACT: In this study we performed ultra deep sequencing of genes associated with anti-EGFR resistance, such as KRAS, BRAF, PIK3CA, and EGFR in 17 plasma-DNA samples from a total of 10 patients treated with anti-EGFR therapy.

PROVIDER: EGAD00001000688 | EGA |

REPOSITORIES: EGA

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Publications

Changes in colorectal carcinoma genomes under anti-EGFR therapy identified by whole-genome plasma DNA sequencing.

Mohan Sumitra S Heitzer Ellen E Ulz Peter P Lafer Ingrid I Lax Sigurd S Auer Martina M Pichler Martin M Gerger Armin A Eisner Florian F Hoefler Gerald G Bauernhofer Thomas T Geigl Jochen B JB Speicher Michael R MR

PLoS genetics 20140327 3

Monoclonal antibodies targeting the Epidermal Growth Factor Receptor (EGFR), such as cetuximab and panitumumab, have evolved to important therapeutic options in metastatic colorectal cancer (CRC). However, almost all patients with clinical response to anti-EGFR therapies show disease progression within a few months and little is known about mechanism and timing of resistance evolution. Here we analyzed plasma DNA from ten patients treated with anti-EGFR therapy by whole genome sequencing (plasma ...[more]

PMID: 24676216

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Project description:The success of targeted therapies creates a need to discriminate tumors accurately by their histological and genetic characteristics. Here, we used cDNA microarray analysis to identify gene expression profiles and single markers that recapitulate the pathological and genetic background (i.e., BRAF, EGFR, KRAS, LKB1, PIK3CA, and TP53 gene alterations) of non-small cell lung cancer (NSCLC). Gene expression profiles were determined for 6 normal lung tissues and 69 lung tumors from patients diagnosed with NSCLC. We performed an unsupervised hierarchical clustering with the most variably expressed transcript to investigate whether there was evidence for natural grouping samples based on similarity in gene expression profiles. We examined the relationship between the clusters of tumors and patient and tumor characteristics such as gender, smoking status, histological type, degree of differentiation, tumor size, lymph node involvement and genetic background. We used a supervised analysis to identify the genes that are important for distinguishing subgroups of tumors defined by histological type. Moreover, we used this supervised approach to search for markers that characterize those tumors carrying EGFR, KRAS, PIK3CA and TP53 alterations. We identify several genes with characteristic patterns of expression in each tumor histological type (adenocarcinoma and squamous cell carcinoma) and we found that the presence of EGFR mutations result in a particular expression profile. Keywords: Transciption profiling of tumors with different histological and genetic background. We analyzed 69 NSCLC tumors. All the samples were characterized by histological type and by the presence of alterations at genes that are known to be involved in lung carcinogenesis. Mutational analysis of BRAF, EGFR, KRAS, and LKB1 is provided only for adenocarcinomas and analysis of alterations at PIK3CA gene (mutational analysis or gene amplification by FISH analysis) is provided only for 47 of the tumors. We analyzed gene expression profiles to identify those genes that are differentially expressed between two subgroups by t-test: 1) adenocarcinomas vs. squamous cell carcinomas; 2) tumors with mutation at EGFR gene vs. wild type tumors; 3) tumors with mutation at KRAS gene vs. wild type tumors; 4) tumors with mutation at TP53 gene vs. wild type tumors; 5) tumors with alterations (mutation or gene amplification) at PIK3CA gene vs. wild type tumors.

Dataset Information

Ena-DATASET-MUG-29-10-2013-10:52:10:827-14 - samples

Publications

Changes in colorectal carcinoma genomes under anti-EGFR therapy identified by whole-genome plasma DNA sequencing.

Similar Datasets

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