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MAPK7 and MAP2K4 as prognostic markers in osteosarcoma

  • Francine Tesser-Gamba, MSc

      Affiliations

    • Department of Pediatrics, Pediatric Oncology Institute (Grupo de Apoio ao Adolescente e à Criança com Câncer), Federal University of São Paulo, São Paulo, SP 04023-062, Brazil
    • Department of Morphology and Genetics, Federal University of São Paulo, São Paulo, SP 04023-062, Brazil
  • ,
  • Antonio Sergio Petrilli, MD, PhD

      Affiliations

    • Department of Pediatrics, Pediatric Oncology Institute (Grupo de Apoio ao Adolescente e à Criança com Câncer), Federal University of São Paulo, São Paulo, SP 04023-062, Brazil
  • ,
  • Maria Teresa de Seixas Alves, MD, PhD

      Affiliations

    • Department of Pediatrics, Pediatric Oncology Institute (Grupo de Apoio ao Adolescente e à Criança com Câncer), Federal University of São Paulo, São Paulo, SP 04023-062, Brazil
    • Department of Pathology, Federal University of São Paulo, São Paulo, SP 04023-062, Brazil
  • ,
  • Reynaldo Jesus Garcia Filho, MD, PhD

      Affiliations

    • Department of Orthopedic Surgery and Traumatology, Federal University of São Paulo, São Paulo, SP 04023-062, Brazil
  • ,
  • Yara Juliano, PhD

      Affiliations

    • Department of Public Health, University of Santo Amaro, São Paulo, SP 04829-300, Brazil
  • ,
  • Sílvia Regina Caminada Toledo, PhD

      Affiliations

    • Department of Pediatrics, Pediatric Oncology Institute (Grupo de Apoio ao Adolescente e à Criança com Câncer), Federal University of São Paulo, São Paulo, SP 04023-062, Brazil
    • Department of Morphology and Genetics, Federal University of São Paulo, São Paulo, SP 04023-062, Brazil
    • Corresponding Author InformationCorresponding author. Pediatrics Oncology Institute (Grupo de Apoio ao Adolescente e à Criança com Câncer), Federal University of São Paulo, Rua Botucatu, São Paulo, SP 04023-062, Brazil.

Received 15 April 2011; received in revised form 10 August 2011; accepted 12 August 2011. published online 12 December 2011.
Corrected Proof

Summary 

Osteosarcoma is a class of cancer originating from the bone, affecting mainly children and young adults. Cytogenetic studies showed the presence of rearrangements and recurrent gains in specific chromosomal regions, indicating the possible involvement of genes located in these regions during the pathogenesis of osteosarcoma. These studies investigated expression of 10 genes located in the chromosomal region involved in abnormalities in osteosarcoma, 1p36, 17p, and chromosome 19. The purpose of this study was to investigate the expression profile of genes located in regions involved in chromosomal rearrangements in osteosarcoma. We used quantitative real-time polymerase chain reaction to investigate the expression of 10 genes located in 1p36.3 (MTHFR, ERRFI1, FGR, E2F2), 17p (MAPK7, MAP2K4), and chromosome 19 (BBC3, FOSB, JUND, and RRAS), in 70 samples taken from 30 patients (30 prechemotherapy, 30 postchemotherapy, and 10 metastases specimens) and 10 healthy bones as a control sample. The most interesting results showed a strong association between the expression levels of MAPK7 and MAP2K4 genes and clinical parameters of osteosarcoma. Overexpression of these genes was significantly associated to a poor response to treatment (P = .0001 and P = .0049, respectively), tumor progression, and worse overall survival (P = .0052 and P = .0085, respectively), suggesting that MAPK7 and MAP2K4 could play an important role in osteosarcoma tumorigenesis. Thus, these genes could be good markers in assessing response to treatment and development of osteosarcoma.

Keywords: Osteosarcoma (OS), Gene expression, OS markers, MAPK7, MAP2K4

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 This study was supported by Fundação de Amparo a Pesquisa do Estado de São Paulo (São Paulo, Brazil), Grant nos. 07/53869-3 and 07/02693-2, and Grupo de Apoio ao Adolescente e à Criança com Câncer/Federal University of São Paulo (São Paulo, Brazil).

PII: S0046-8177(11)00339-X

doi:10.1016/j.humpath.2011.08.003

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