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Sequencing of RAS/RAF pathway genes in primary colorectal cancer and matched liver and lung metastases
Knijn, Nikki; Water, Carlijn van de; Vliet, Shannon van; Meijer, Jos; Riemersma, Sietske; Tebar, Maria; Punt, Cornelis; Mekenkamp, Leonie; Simmer, Femke; Nagtegaal, Iris.
  • Knijn, Nikki; Radboud University Medical Center. Nijmegen. NL
  • Water, Carlijn van de; Radboud University Medical Center. Nijmegen. NL
  • Vliet, Shannon van; Radboud University Medical Center. Nijmegen. NL
  • Meijer, Jos; Department of Pathology, Rijnstate Hospital, Arnhem. Arnhem. NL
  • Riemersma, Sietske; Laboratory of Pathology East Netherlands. Hengelo. NL
  • Tebar, Maria; Laboratory of Pathology East Netherlands. Hengelo. NL
  • Punt, Cornelis; Department of Medical Oncology, Academic Medical Center, University of Amsterdam. Amsterdam. NL
  • Mekenkamp, Leonie; Department of Medical Oncology, Hospital Medisch Spectrum Twente. Enschede. NL
  • Simmer, Femke; Radboud University Medical Center. Nijmegen. NL
  • Nagtegaal, Iris; Radboud University Medical Center. Nijmegen. NL
Appl. cancer res ; 39: 1-7, 2019. ilustr.
Artigo em Inglês | LILACS, Inca | ID: biblio-1023627
ABSTRACT

Background:

Mutations in the RAS/RAF pathway predict resistance to anti-epidermal growth factor receptor antibodies in colorectal cancer (CRC), and may be targets for future therapies. This study investigates concordance of BRAF, HRAS, KRAS, NRAS and PIK3CA mutation status in primary CRC with matched liver (n = 274), lung (n = 114) or combined liver and lung metastases (n = 14).

Methods:

Next generation sequencing was performed on DNA from formalin-fixed paraffin embedded CRC and matched liver and/or lung metastases, for recurrent mutations in BRAF, HRAS, KRAS, NRAS and PIK3CA and using the single-molecule molecular inversion probe method.

Results:

Paired sequencing results on all five genes were reached in 249 of the 402 cases (62%). The obtained number of unique reads was not always sufficient to confidently call the absence or presence of mutations for all regions of interest. The mutational status of matched pairs was highly concordant; 91.1% concordance for all five genes, 95.5% for KRAS, 99.1% for NRAS. Lung metastases more often harboured RAS mutations compared to liver metastases (71% vs. 48%, p < 0.001).

Conclusions:

In this large series of CRC we show that both primary tumors and corresponding metastases can be used to determine the mutational status for targeted therapy, given the high concordance rates. Next generation sequencing including a single molecule tags is feasible, however in combination with archival formalin-fixed paraffin embedded material is limited by coverage depth.
Assuntos


Texto completo: DisponíveL Índice: LILACS (Américas) Assunto principal: Neoplasias Colorretais / Proteínas ras / Proteínas Proto-Oncogênicas B-raf / Neoplasias Hepáticas / Neoplasias Pulmonares Tipo de estudo: Estudo prognóstico Limite: Humanos Idioma: Inglês Revista: Appl. cancer res Assunto da revista: Neoplasias Ano de publicação: 2019 Tipo de documento: Artigo País de afiliação: Holanda Instituição/País de afiliação: Department of Medical Oncology, Academic Medical Center, University of Amsterdam/NL / Department of Medical Oncology, Hospital Medisch Spectrum Twente/NL / Department of Pathology, Rijnstate Hospital, Arnhem/NL / Laboratory of Pathology East Netherlands/NL / Radboud University Medical Center/NL

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Texto completo: DisponíveL Índice: LILACS (Américas) Assunto principal: Neoplasias Colorretais / Proteínas ras / Proteínas Proto-Oncogênicas B-raf / Neoplasias Hepáticas / Neoplasias Pulmonares Tipo de estudo: Estudo prognóstico Limite: Humanos Idioma: Inglês Revista: Appl. cancer res Assunto da revista: Neoplasias Ano de publicação: 2019 Tipo de documento: Artigo País de afiliação: Holanda Instituição/País de afiliação: Department of Medical Oncology, Academic Medical Center, University of Amsterdam/NL / Department of Medical Oncology, Hospital Medisch Spectrum Twente/NL / Department of Pathology, Rijnstate Hospital, Arnhem/NL / Laboratory of Pathology East Netherlands/NL / Radboud University Medical Center/NL