Concomitant RAS and BRAF mutation in colorectal cancer - A report of 7 cases


Ates O., YALÇIN Ş.

INDIAN JOURNAL OF CANCER, vol.56, no.2, pp.176-179, 2019 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 56 Issue: 2
  • Publication Date: 2019
  • Doi Number: 10.4103/ijc.ijc_430_18
  • Title of Journal : INDIAN JOURNAL OF CANCER
  • Page Numbers: pp.176-179

Abstract

Rat sarcoma viral oncogene homolog (RAS) and B-Raf murine sarcoma viral oncogene homolog B1 (BRAF) are members of the same signaling pathway (RAS-RAF-mitogen-activated protein kinase (MAPK) in colorectal cancer (CRC). It is generally assumed that BRAF mutations are seen only with wild-type RAS in CRC. But RAS and BRAF are not mutually exclusive. We have identified concomitant BRAF and RAS mutations in seven patients. DNA was extracted from formalin-fixed paraffin-embedded tumor tissue and the mutation status of the RAS gene (exons 2, 3, 4) and BRAF (exon 15 V600, V597) was assessed using a polymerase chain reaction enzyme-linked mini sequence assay-based DNA sequencing method. Three patients harbored Kirsten rat sarcoma viral oncogene homolog (KRAS) with a codon 13 mutation (gly13asp) along with a BRAF variation of L597V in exon 15 (p. leu597val, c.1789C>G (CTA>GTA). Two patients harbored KRAS with codon 12 mutations; one harbored the gly12val mutation with a variation of leu597val in the BRAF exon 15 codon, the other harbored a gly12asp mutation with p. leu597val, c.1789C>G (CTA>GTA) in the BRAF exon 15 codon. One patient harbored a codon 117 mutation with a BRAF V600E mutation. The last patient harbored a NRAS exon 2 (gly12asp) mutation with the GGT/GAT, V600G mutation in the BRAF exon 15 codon. Consequently, concomitant KRAS and BRAF mutations are very rare. Although it is known that the survival of concomitant RAS/BRAF mutation carriers is generally poor, we have shown that survival of concomitant RAS/BRAF mutation carriers is variable.