Department of Pathology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Department of Surgery, Queen Ingrid's Hospital, Nuuk, Greenland.
APMIS. 2022 Aug;130(8):493-497. doi: 10.1111/apm.13254. Epub 2022 Jun 20.
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.
KRAS 突变是结直肠癌(CRC)中最常见的驱动突变之一,也是一种预后生物标志物。本研究旨在确定在被诊断患有 CRC 的格陵兰人群中,KRAS 突变随时间的频率。在 1988 年至 2017 年间,共确定了 578 例腺癌患者。在 1988-1990 年、2002-2004 年和 2015-2017 年期间,通过 Idylla™平台在 102 个代表性样本中确定了 KRAS 状态和 KRAS 突变的突变亚型。结果表明,KRAS 突变的频率显著增加,从 1988-1990 年的 27%增加到 2015-2017 年的 43%(p<0.001)。此外,在格陵兰最常见的 KRAS 突变亚型是 G12D(c.35G>A),占 14%,G12V(c.35G>T)占 7%,G13D(c.38G>A)占 6%。总之,本研究表明,在最近几十年,特定的格陵兰人群中 CRC 中 KRAS 突变的频率一直在增加。本研究的结果可用于与特定种族的 CRC 靶向治疗相关的举措,以及与癌症相关体细胞突变的环境因素相关的研究。