Biopolym. Cell. 2015; 31(6):436-446.
http://dx.doi.org/10.7124/bc.000901
Genomics, Transcriptomics and Proteomics
NGS-based identification of druggable alterations and signaling pathways – hepatocellular carcinoma case report
1, 5Kotelnikova E. A., 1, 2Logacheva M. D., 2Nabieva E. R., 3, 5Pyatnitskiy M. A., 1, 5Vinogradov D. V., 2, 4, 5Makarova A. S., 5Demin A. V., 5Paleeva A. G., 5, 6Kremenetskaya O. S., 1, 2, 7Penin A. A., 1, 2Klepikova A. V., 2Kasianov A. S., 4Shavochkina D. A., 4Kudashkin N. E., 4Patyutko Yu. I., 2, 5Mugue N. S., 2Kondrashov A. S., 4, 7Lazarevich N. L
  1. A. A. Kharkevich Institute for Information Transmission Problems,
    19/1, Bolshoy Karetny per. Moscow, Russian Federation, 127051
  2. A. N. Belozersky Institute of Physico-Chemical Biology, M. V. Lomonosov Moscow State University
    Leninskie gory, house 1, building 40, Moscow, Russian Federation, 119992
  3. Orekhovich Institute of Biomedical Chemistry,
    10/8, Pogodinskaya Str., Moscow, Russian Federation, 119121
  4. N. N. Blokhin Russian Cancer Research Centre, RAMS
    24, Kashirskoye shosse, Moscow, Russian Federation, 115478
  5. ZAO Personal Biomedicine,
    124/17, Prospekt Mira, Moscow, Russian Federation, 129164
  6. Center for Theoretical Problems of Physicochemical Pharmacology RAS,
    4, Kosygin Str., Moscow, Russian Federation, 119991
  7. M. V. Lomonosov Moscow State University
    Leninskie Gory, 1/12, Moscow, Russian Federation, 119991

Abstract

Aim. To identify potential cancer driving or clinically relevant molecular events for a patient with hepatocellular carcinoma. Methods. In order to achieve this goal, we performed RNA-seq and exome sequencing for the tumor tissue and its matched control. We annotated the alterations found using several publicly available databases and bioinformatics tools. Results. We identified several differentially expressed genes linked to the classical sorafenib treatment as well as additional pathways potentially druggable by therapies studied in clinical trials (Erlotinib, Lapatinib and Temsirolimus). Several germline mutations, found in XRCC1, TP53 and DPYD, according to the data from other clinical trials, could be related to the increased sensitivity to platinum therapies and reduced sensitivity to 5-Fluorouracil. We also identified several potentially driving mutations that could not be currently linked to therapies, like deletion in CIRBP, SNVs in BTG1, ERBB3, TCF7L2 et al. Conclusions. The presented study shows the potential usefulness of the integrated approach to the NGS data analysis, including the analysis of germline mutations and transcriptome in addition to the cancer panel or the exome sequencing data.
Keywords: NGS, cancer, systems biology, pathways, pharmacogenetics, personalized medicine
Full text: (PDF, in English)

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