Cross-cancer profiling of molecular alterations within the human autophagy interaction network
| العنوان: | Cross-cancer profiling of molecular alterations within the human autophagy interaction network |
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| المؤلفون: | Rodrigo Goya, Chandra Lebovitz, Sharon M. Gorski, Marco A. Marra, A. Gordon Robertson, Steven J.M. Jones, Ryan D. Morin |
| المصدر: | Autophagy |
| بيانات النشر: | Informa UK Limited, 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Resource, autophagy, tumor, Transcription, Genetic, Biology, Bioinformatics, medicine.disease_cause, Polymorphism, Single Nucleotide, Breast cancer, LAPTM4B, AML, Mutation Rate, Neoplasms, SNV, medicine, Carcinoma, cancer, Cluster Analysis, Humans, SQSTM1, Gene Regulatory Networks, RNA, Messenger, Molecular Biology, PI3K/AKT/mTOR pathway, Gene Expression Profiling, Autophagy, Cell Biology, TCGA, medicine.disease, Survival Analysis, 3. Good health, Gene Expression Regulation, Neoplastic, Gene expression profiling, Case-Control Studies, gene expression, Cancer research, mutation, Carcinogenesis, Kidney cancer |
| الوصف: | Aberrant activation or disruption of autophagy promotes tumorigenesis in various preclinical models of cancer, but whether the autophagy pathway is a target for recurrent molecular alteration in human cancer patient samples is unknown. To address this outstanding question, we surveyed 211 human autophagy-associated genes for tumor-related alterations to DNA sequence and RNA expression levels and examined their association with patient survival outcomes in multiple cancer types with sequence data from The Cancer Genome Atlas consortium. We found 3 (RB1CC1/FIP200, ULK4, WDR45/WIPI4) and one (ATG7) core autophagy genes to be under positive selection for somatic mutations in endometrial carcinoma and clear cell renal carcinoma, respectively, while 29 autophagy regulators and pathway interactors, including previously identified KEAP1, NFE2L2, and MTOR, were significantly mutated in 6 of the 11 cancer types examined. Gene expression analyses revealed that GABARAPL1 and MAP1LC3C/LC3C transcripts were less abundant in breast cancer and non-small cell lung cancers than in matched normal tissue controls; ATG4D transcripts were increased in lung squamous cell carcinoma, as were ATG16L2 transcripts in kidney cancer. Unsupervised clustering of autophagy-associated mRNA levels in tumors stratified patient overall survival in 3 of 9 cancer types (acute myeloid leukemia, clear cell renal carcinoma, and head and neck cancer). These analyses provide the first comprehensive resource of recurrently altered autophagy-associated genes in human tumors, and highlight cancer types and subtypes where perturbed autophagy may be relevant to patient overall survival. |
| تدمد: | 1554-8635 1554-8627 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::28a9532153b371800cd66598fe641f6fTest https://doi.org/10.1080/15548627.2015.1067362Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....28a9532153b371800cd66598fe641f6f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15548635 15548627 |
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