Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Genomic profiling of patient-derived xenografts identify high level âpassengerâ gene aberrations associated with better prognosis in non-small cell lung cancer

ABSTRACT: Patient-derived tumor xenografts (PDXs) increasingly are being used as preclinical models to study human cancers and to evaluate novel therapeutics, as they reflect clinical cancers more closely than established tumor cell lines. With >100 PDXs established from resected non-small cell lung carcinomas (NSCLC), we reported previously that xenograftability correlates significantly with poorer patient prognosis. In this study, genomic, transcriptomic, and proteomic profiling of 36 PDXs showed greater similarity in somatic alterations between PDX and primary tumors than with cell lines, using publicly available data on the latter. A higher number of somatic alterations among 865 frequently altered genes in the PDX tumors was associated with better overall patient survival (HR=0.15, p=0.00015) compared to patients with corresponding PDXs characterized by a lower number of alterations; this was validated with the TCGA lung cancer patient dataset (HR=0.28, p=0.000022). These passenger-like alterations, identified in PDXs, link cell-cell signaling and adhesion to patient prognosis. Total RNAs from xenograftswere amplified by DASL kit and hybridized to Illumina HT12v4 chip

ORGANISM(S): Mus musculus

SUBMITTER: Ming Tsao

PROVIDER: E-GEOD-68929 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Molecular heterogeneity of non-small cell lung carcinoma patient-derived xenografts closely reflect their primary tumors.

Wang Dennis D Pham Nhu-An NA Tong Jiefei J Sakashita Shingo S Allo Ghassan G Kim Lucia L Yanagawa Naoki N Raghavan Vibha V Wei Yuhong Y To Christine C Trinh Quang M QM Starmans Maud H W MH Chan-Seng-Yue Michelle A MA Chadwick Dianne D Li Lei L Zhu Chang-Qi CQ Liu Ni N Li Ming M Lee Sharon S Ignatchenko Vladimir V Strumpf Dan D Taylor Paul P Moghal Nadeem N Liu Geoffrey G Boutros Paul C PC Kislinger Thomas T Pintilie Melania M Jurisica Igor I Shepherd Frances A FA McPherson John D JD Muthuswamy Lakshmi L Moran Michael F MF Tsao Ming-Sound MS

International journal of cancer 20161107 3

Availability of lung cancer models that closely mimic human tumors remains a significant gap in cancer research, as tumor cell lines and mouse models may not recapitulate the spectrum of lung cancer heterogeneity seen in patients. We aimed to establish a patient-derived tumor xenograft (PDX) resource from surgically resected non-small cell lung cancer (NSCLC). Fresh tumor tissue from surgical resection was implanted and grown in the subcutaneous pocket of non-obese severe combined immune deficie ...[more]

PMID: 27750381

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Dataset Information

Genomic profiling of patient-derived xenografts identify high level âpassengerâ gene aberrations associated with better prognosis in non-small cell lung cancer

Publications

Molecular heterogeneity of non-small cell lung carcinoma patient-derived xenografts closely reflect their primary tumors.

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Genomic profiling of patient-derived xenografts identify high level âpassengerâ gene aberrations associated with better prognosis in non-small cell lung cancer