잠시만 기다려 주세요. 로딩중입니다.

KRAS, NRAS, and BRAF mutations in plasma cell myeloma at a single Korean institute

Blood Research 2020년 55권 3호 p.159 ~ 168
김용구, 박성수, 민창기, 이건동, 손정옥, 조성진, 한은희, 한경자, 김명신,
소속 상세정보
김용구 ( Kim Yong-Goo ) - Catholic University Seoul St. Mary’s Hospital Catholic Genetic Laboratory Center
박성수 ( Park Sung-Soo ) - Catholic University College of Medicine Seoul St. Mary’s Hospital Department of Hematology
민창기 ( Min Chang-Ki ) - Catholic University College of Medicine Seoul St. Mary’s Hospital Department of Hematology
이건동 ( Lee Gun-Dong ) - Catholic University Seoul St. Mary’s Hospital Catholic Genetic Laboratory Center
손정옥 ( Son Jung-Ok ) - Catholic University Seoul St. Mary’s Hospital Catholic Genetic Laboratory Center
조성진 ( Jo Sung-Jin ) - Catholic University College of Medicine Department of Laboratory Medicine
한은희 ( Han Eun-Hee ) - Catholic University College of Medicine Department of Laboratory Medicine
한경자 ( Han Kyung-Ja ) - Catholic University College of Medicine Department of Laboratory Medicine
김명신 ( Kim Myung-Shin ) - Catholic University College of Medicine Department of Laboratory Medicine

Abstract


Background: Plasma cell myeloma (PCM) is a genetically heterogeneous disease. The genetic spectrum of PCM has been expanded to mutations such as KRAS, NRAS, and BRAF genes in the RAS-RAF-MAPK pathway. In this study, we have evaluated the frequency of these mutations and their significance, including baseline characteristics and clinical outcomes.

Methods: We explored 50 patients who were newly diagnosed with PCM between 2009 and 2012 at a single Korean institute. Clinical and laboratory parameters were gathered through careful review of medical records. Mutation analysis was carried out using DNA from the bone marrow at the time of diagnosis. Pyrosequencing was performed to detect KRAS G12V, KRAS G13D, and NRAS G61R. BRAF V600E was analyzed by allele-specific real- time PCR. Comparison of clinical and laboratory parameters was carried out according to those mutations.

Results: We identified 14 patients (28%) with activating mutations in the RAS-RAF-MAPK pathway (RAS/RAF mutations): KRAS (N=3), NRAS (N=4), BRAF (N=7), and both KRAS and BRAF (N=1). RAS/RAF mutations were more frequently observed in patients with complex karyotypes and showed poorer progression free survival (PFS). Specifically, the BRAF V600E mutation had a significantly negative impact on median PFS.

Conclusion: We first showed the frequency of RAS/RAF mutations in Korean patients with PCM. Screening of these mutations could be considered as a routine clinical test at the time of diagnosis and follow-up due to their influence on clinical outcome, as well as its potential as a therapeutic target.

키워드

KRAS; NRAS; BRAF; Plasma cell myeloma

원문 및 링크아웃 정보

등재저널 정보