title: miRNA profiling, detection of BRAF V600E mutation and RET-PTC1 translocation in patients from Novosibirsk oblast (Russia) with different types of thyroid tumors.
abstract: BACKGROUND
  The postoperative typing of thyroid lesions, which is instrumental in adequate patient treatment, is currently based on histologic examination. However, it depends on pathologist's qualification and can be difficult in some cases. Numerous studies have shown that molecular markers such as microRNAs and somatic mutations may be useful to assist in these cases, but no consensus exists on the set of markers that is optimal for that purpose. The aim of the study was to discriminate between different thyroid neoplasms by RT-PCR, using a limited set of microRNAs selected from literature.
  
  
  METHODS
  By RT-PCR we evaluated the relative levels of 15 microRNAs (miR-221, -222, -146b, -181b, -21, -187, -199b, -144, -192, -200a, -200b, -205, -141, -31, -375) and the presence of BRAF(V600E) mutation and RET-PTC1 translocation in surgically resected lesions from 208 patients from Novosibirsk oblast (Russia) with different types of thyroid neoplasms. Expression of each microRNA was normalized to adjacent non-tumor tissue. Three pieces of lesion tissue from each patient (39 goiters, 41 follicular adenomas, 16 follicular thyroid cancers, 108 papillary thyroid cancers, 4 medullary thyroid cancers) were analyzed independently to take into account method variation.
  
  
  RESULTS
  The diagnostic classifier based on profiling of 13 microRNAs was proposed, with total estimated accuracy varying from 82.7 to 99% for different nodule types. Relative expression of six microRNAs (miR-146b, -21, -221, -222, 375, -199b) appeared significantly different in BRAF(V600E)-positive samples (all classified as papillary thyroid carcinomas) compared to BRAF(V600E)-negative papillary carcinoma samples.
  
  
  CONCLUSIONS
  The results confirm practical feasibility of using molecular markers for typing of thyroid neoplasms and clarification of controversial cases.
authors.affiliation: Institute of Molecular and Cellular Biology, SB RAS, Novosibirsk, Russia. titovse78@gmail.com.|JSC "Vector-Best", Koltsovo, Russia. titovse78@gmail.com.
authors.forename: Sergei E
authors.initials: SE
authors.lastname: Titov
authors.affiliation: JSC "Vector-Best", Koltsovo, Russia.
authors.forename: Mikhail K
authors.initials: MK
authors.lastname: Ivanov
authors.affiliation: Novosibirsk Municipal Budgetary Healthcare Institution "Municipal Clinical Hospital #1", Novosibirsk, Russia.
authors.forename: Elena V
authors.initials: EV
authors.lastname: Karpinskaya
authors.affiliation: JSC "Vector-Best", Koltsovo, Russia.
authors.forename: Elena V
authors.initials: EV
authors.lastname: Tsivlikova
authors.affiliation: Novosibirsk Municipal Budgetary Healthcare Institution "Municipal Clinical Hospital #1", Novosibirsk, Russia.
authors.forename: Sergei P
authors.initials: SP
authors.lastname: Shevchenko
authors.affiliation: Institute of Molecular and Cellular Biology, SB RAS, Novosibirsk, Russia.
authors.forename: Yulia A
authors.initials: YA
authors.lastname: Veryaskina
authors.affiliation: Institute of Molecular and Cellular Biology, SB RAS, Novosibirsk, Russia.
authors.forename: Larisa G
authors.initials: LG
authors.lastname: Akhmerova
authors.affiliation: Non-governmental Healthcare Institution «Railroad Clinical Hospital on the Station Novosibirsk-Glavny", JSC Russian Railways, Novosibirsk, Russia.
authors.forename: Tatiana L
authors.initials: TL
authors.lastname: Poloz
authors.affiliation: Institute of Molecular and Cellular Biology, SB RAS, Novosibirsk, Russia.|JSC "Vector-Best", Koltsovo, Russia.
authors.forename: Olesya A
authors.initials: OA
authors.lastname: Klimova
authors.affiliation: Institute of Molecular Biology and Biophysics, SB RAMS, Novosibirsk, Russia.
authors.forename: Lyudmila F
authors.initials: LF
authors.lastname: Gulyaeva
authors.affiliation: Institute of Molecular and Cellular Biology, SB RAS, Novosibirsk, Russia.
authors.forename: Igor F
authors.initials: IF
authors.lastname: Zhimulev
authors.affiliation: Institute of Molecular and Cellular Biology, SB RAS, Novosibirsk, Russia.
authors.forename: Nikolay N
authors.initials: NN
authors.lastname: Kolesnikov
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics*; D002277:Carcinoma / Q000235:genetics / Q000473:pathology; D018278:Carcinoma, Neuroendocrine / Q000235:genetics / Q000473:pathology; D002291:Carcinoma, Papillary; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012426:Russia; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology; D014178:Translocation, Genetic / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; D015514:Oncogene Proteins, Fusion; D011505:Protein-Tyrosine Kinases; C093573:ret-PTC fusion oncoproteins, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf