Sequencing of RAS/RAF pathway genes in primary colorectal cancer and matched liver and lung metastases
Appl. cancer res
;
39: 1-7, 2019. ilustr.
Artículo
en Inglés
| 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.
Texto completo:
Disponible
Índice:
LILACS (Américas)
Asunto principal:
Neoplasias Colorrectales
/
Proteínas ras
/
Proteínas Proto-Oncogénicas B-raf
/
Neoplasias Hepáticas
/
Neoplasias Pulmonares
Tipo de estudio:
Estudio pronóstico
Límite:
Humanos
Idioma:
Inglés
Revista:
Appl. cancer res
Asunto de la revista:
Neoplasmas
Año:
2019
Tipo del documento:
Artículo
País de afiliación:
Países Bajos
Institución/País de afiliación:
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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