title: High copy number variation of cancer-related microRNA genes and frequent amplification of DICER1 and DROSHA in lung cancer.
abstract: A growing body of evidence indicates that miRNAs may be a class of genetic elements that can either drive or suppress oncogenesis. In this study we analyzed the somatic copy number variation of 14 miRNA genes frequently found to be either over- or underexpressed in lung cancer, as well as two miRNA biogenesis genes, DICER1 and DROSHA, in non-small-cell lung cancer (NSCLC). Our analysis showed that most analyzed miRNA genes undergo substantial copy number alteration in lung cancer. The most frequently amplified miRNA genes include the following: miR-30d, miR-21, miR-17 and miR-155. We also showed that both DICER1 and DROSHA are frequently amplified in NSCLC. The copy number variation of DICER1 and DROSHA correlates well with their expression and survival of NSCLC and other cancer patients. The increased expression of DROSHA and DICER1 decreases and increases the survival, respectively. In conclusion, our results show that copy number variation may be an important mechanism of upregulation/downregulation of miRNAs in cancer and suggest an oncogenic role for DROSHA.
authors.affiliation: European Centre for Bioinformatics and Genomics, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland.
authors.forename: Karol
authors.initials: K
authors.lastname: Czubak
authors.affiliation: Molecular Oncology and Genetics Department, Innovative Medical Forum, The Franciszek Lukaszczyk Oncology Center, Bydgoszcz, Poland.|Department of Thoracic Surgery and Tumors, Nicolaus Copernicus University, Torun, Collegium Medicum, Bydgoszcz, Poland.
authors.forename: Marzena Anna
authors.initials: MA
authors.lastname: Lewandowska
authors.affiliation: European Centre for Bioinformatics and Genomics, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Klonowska
authors.affiliation: Department of Radiotherapy, The Franciszek Lukaszczyk Oncology Center, Bydgoszcz, Poland.|Department of Oncology, Radiotherapy and Gynecologic Oncology, Nicolaus Copernicus University, Torun, Collegium Medicum, Bydgoszcz, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Roszkowski
authors.affiliation: Department of Thoracic Surgery and Tumors, Nicolaus Copernicus University, Torun, Collegium Medicum, Bydgoszcz, Poland.|Department of Thoracic Surgery and Tumors, The Franciszek Lukaszczyk Oncology Center, Bydgoszcz, Poland.
authors.forename: Janusz
authors.initials: J
authors.lastname: Kowalewski
authors.affiliation: European Centre for Bioinformatics and Genomics, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Figlerowicz
authors.affiliation: European Centre for Bioinformatics and Genomics, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Kozlowski
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D018628:Gene Dosage; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D012189:Retrospective Studies; D043244:Ribonuclease III / Q000378:metabolism*; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: D035683:MicroRNAs; C408087:DICER1 protein, human; C517918:DROSHA protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases
keywords: DICER1; DROSHA; MLPA; microRNA; non-small cell lung cancer NSCLC