Wenqi Li1, Huining Li2,3, Ruiqi Liu4, Xinxin Yang1, Yuhui Gao1, Yangyang Niu1, Jiashi Geng5, Yingwei Xue6, Xiaoming Jin3, Qi You6, Jingshu Geng1,3, Hongxue Meng7,8,9. 1. Department of Pathology, Harbin Medical University Cancer Hospital, Harbin, China. 2. Department of Pathology, The First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, China. 3. Department of Pathology, Harbin Medical University, Harbin, China. 4. Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China. 5. Department of Radiology, Harbin Medical University Cancer Hospital, Harbin, China. 6. Department of Gastroenterology, Harbin Medical University Cancer Hospital, Harbin, China. 7. Department of Pathology, Harbin Medical University Cancer Hospital, Harbin, Chinamenghongxue15@163.com. 8. Department of Pathology, The First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, Chinamenghongxue15@163.com. 9. Department of Pathology, Harbin Medical University, Harbin, Chinamenghongxue15@163.com.
Abstract
BACKGROUND/AIMS: Colorectal cancer (CRC) is mainly caused by chromosomal instability (CIN) and microsatellite instability (MSI). The RAS and RAF genes are essential components of the CIN pathway, and several studies have found that RAS and RAF mutations are associated with MSI status in CRC. Here, we examined these three factors in CRC in Northeast China and aimed to reveal new details of the relationship between these mutations and MSI status. METHODS: This study involved 290 patients with CRC who had RAS or RAF gene mutation detected using fluorescence-based allele-specific polymerase chain reaction or Sanger sequencing. The majority of the identified patients were found to harbor MSI (MSI status). Accurate molecular detection was carried out using formalin-fixed paraffin-embedded tissue or blood samples. RESULTS: The rates of RAS and RAF mutations were 58.5% and 4.1%, respectively. The prevalence of RAS mutation in CRC was clearly higher and that of RAF mutation was lower in Northeast China compared with previously reported cohorts in other locations. High MSI level (MSI-H status) was more complex, at around 10%. This was consistent with previous data from China. However, compared with data reported from other continents, MSI-H was higher than that of Japan or South Korea in Asia, and lower than that of Europe or the United States. CONCLUSION: RAS/RAF mutations and MSI status in CRC are closely associated with tumor location and ethnicity. Further studies investigating the relationship between these three factors can help in the development of treatment strategies for patients with CRC.
BACKGROUND/AIMS: Colorectal cancer (CRC) is mainly caused by chromosomal instability (CIN) and microsatellite instability (MSI). The RAS and RAF genes are essential components of the CIN pathway, and several studies have found that RAS and RAF mutations are associated with MSI status in CRC. Here, we examined these three factors in CRC in Northeast China and aimed to reveal new details of the relationship between these mutations and MSI status. METHODS: This study involved 290 patients with CRC who had RAS or RAF gene mutation detected using fluorescence-based allele-specific polymerase chain reaction or Sanger sequencing. The majority of the identified patients were found to harbor MSI (MSI status). Accurate molecular detection was carried out using formalin-fixed paraffin-embedded tissue or blood samples. RESULTS: The rates of RAS and RAF mutations were 58.5% and 4.1%, respectively. The prevalence of RAS mutation in CRC was clearly higher and that of RAF mutation was lower in Northeast China compared with previously reported cohorts in other locations. High MSI level (MSI-H status) was more complex, at around 10%. This was consistent with previous data from China. However, compared with data reported from other continents, MSI-H was higher than that of Japan or South Korea in Asia, and lower than that of Europe or the United States. CONCLUSION: RAS/RAF mutations and MSI status in CRC are closely associated with tumor location and ethnicity. Further studies investigating the relationship between these three factors can help in the development of treatment strategies for patients with CRC.
Authors: Fatima El Agy; Sanae El Bardai; Ihsane El Otmani; Zineb Benbrahim; Ibn Majdoub Hassani Karim; Khalid Mazaz; El Bachir Benjelloun; Abdelmalek Ousadden; Mohammed El Abkari; Sidi Adil Ibrahimi; Laila Chbani Journal: PLoS One Date: 2021-03-30 Impact factor: 3.240