Mutation of KRAS in colorectal adenocarcinoma in Greenland

Abstract

KRAS mutation is one of the most frequent driver mutations in colorectal cancer (CRC) and is also a prognostic biomarker. The aim of the present study was to determine the frequency of KRAS mutations over time in the Greenlandic population diagnosed with CRC. In total, 578 patients with the diagnosis of adenocarcinoma between 1988 and 2017 were identified. The status of KRAS and the mutational subtypes of KRAS mutations were determined in 102 representative samples by the Idylla™ platform in the time periods 1988–1990, 2002–2004, and 2015–2017. The results showed that the frequency of the KRAS mutations increased significantly, from 27% in 1988–1990 to 43% in 2015–2017 (p < 0.001). Furthermore, the most frequent subtypes of KRAS mutations in Greenland were G12D (c.35G > A) with 14%, G12V (c.35G > T) with 7%, and G13D (c.38G > A) with 6%. In conclusion, this study showed that the frequency of KRAS mutations in CRC has been increasing in recent decades in the specific population of Greenland. The results of this study may be used in initiatives related to targeted therapy of CRC in specific ethnicities and in investigations focusing on the environmental factors of cancer‐related somatic mutations.

Targeting KRAS in Colorectal Cancer: A Bench to Bedside Review

“…KRAS itself encodes two highly related protein isoforms, KRAS-4B and KRAS-4A, containing 188 and 189 amino acids, respectively [13,26]. These isoforms are both involved in cell proliferation, differentiation, and cell growth through the RAS/MAPK signaling pathway [27]. Generally, "KRAS" refers to the KRAS-4B isoform due to the high level of mRNA encoding KRAS-4B in cells [28].…”