Contributions
Abstract: PB2118
Type: Publication Only
Background
Multiple myeloma (MM) is an incurable malignancy of plasma cells and the incidence of Taiwan MM has markedly increased in recent decades. There were frequent mutations in KRAS (particularly in previously treated patients), NRAS, BRAF, FAM46C, TP53, and DIS3 genes.
Aims
The study is to examine the prevalence of hotspot gene mutations in Taiwan MM patients by using the DNA from MM bone marrow samples, and further develop so-called liquid biopsy and to detect several hotspot gene mutations in patients’ plasma DNA.
Methods
BM DNA was extracted from 122 MM patients at diagnosis or relapse. In addition, cell-free DNA (ccfDNA) was collected from 24 of these patients at the comparable time of BM collected. Mass Spectrometry was used to simultaneously detect a panel of assay including 26 types of KRAS, 26 types of NRAS and 6 types of BRAF mutations.
Results
We found that total 45 (36.89% of 122) and 50 (40.98% of 122) patients had mutations in KRAS and NRAS genes in the BM, respectively. KRAS_A59T, NRAS_G12S and NRAS_A146T were the most frequent 3 mutations. For 24 ccfDNA, RAS/BRAF mutations were detected in 70.83% (17 of 24) of patients, including 41.67% (10/24), 41.67% (10/24), 4.17% (1/24) patients. The same mutations detected in the plasma of 6 patients could be also seen in the bone marrow. When compared the detection of RAS/BRAF mutations in plasma and bone marrow, 12 patients (50% of 24) had RAS/BRAF mutations detected in both plasma and bone marrow, and 3 patients (12.5% of 24) did not mutations in both specimens. Four patients (16.67%) had mutations only detected in BM, and 5 patients (20.83% of 24) had mutations only detected in the plasma. When RAS/BRAF mutations was detected in the plasma of MM patients by MassArray, the sensitivity and specificity of RAS/BRAF mutations in the bone marrow was 75% and 37.5%, respectively. The positive predictive value and negative predictive value were 70.59% and 42.86%, respectively.
Conclusion
Our study found a comparable mutation rate of RAS/BRAF gene in Taiwan MM patients, when comparing those in recent reports of Western countries. We further used Mass Spectrometry to detect circulating tumor DNA, and one fifth of patients (5 of 24, 20.83%) had mutations only detected in the plasma.
Session topic: 13. Myeloma and other monoclonal gammopathies – Biology & Translational Research
Keyword(s): Multiple Myeloma, mutation analysis, Ras
Abstract: PB2118
Type: Publication Only
Background
Multiple myeloma (MM) is an incurable malignancy of plasma cells and the incidence of Taiwan MM has markedly increased in recent decades. There were frequent mutations in KRAS (particularly in previously treated patients), NRAS, BRAF, FAM46C, TP53, and DIS3 genes.
Aims
The study is to examine the prevalence of hotspot gene mutations in Taiwan MM patients by using the DNA from MM bone marrow samples, and further develop so-called liquid biopsy and to detect several hotspot gene mutations in patients’ plasma DNA.
Methods
BM DNA was extracted from 122 MM patients at diagnosis or relapse. In addition, cell-free DNA (ccfDNA) was collected from 24 of these patients at the comparable time of BM collected. Mass Spectrometry was used to simultaneously detect a panel of assay including 26 types of KRAS, 26 types of NRAS and 6 types of BRAF mutations.
Results
We found that total 45 (36.89% of 122) and 50 (40.98% of 122) patients had mutations in KRAS and NRAS genes in the BM, respectively. KRAS_A59T, NRAS_G12S and NRAS_A146T were the most frequent 3 mutations. For 24 ccfDNA, RAS/BRAF mutations were detected in 70.83% (17 of 24) of patients, including 41.67% (10/24), 41.67% (10/24), 4.17% (1/24) patients. The same mutations detected in the plasma of 6 patients could be also seen in the bone marrow. When compared the detection of RAS/BRAF mutations in plasma and bone marrow, 12 patients (50% of 24) had RAS/BRAF mutations detected in both plasma and bone marrow, and 3 patients (12.5% of 24) did not mutations in both specimens. Four patients (16.67%) had mutations only detected in BM, and 5 patients (20.83% of 24) had mutations only detected in the plasma. When RAS/BRAF mutations was detected in the plasma of MM patients by MassArray, the sensitivity and specificity of RAS/BRAF mutations in the bone marrow was 75% and 37.5%, respectively. The positive predictive value and negative predictive value were 70.59% and 42.86%, respectively.
Conclusion
Our study found a comparable mutation rate of RAS/BRAF gene in Taiwan MM patients, when comparing those in recent reports of Western countries. We further used Mass Spectrometry to detect circulating tumor DNA, and one fifth of patients (5 of 24, 20.83%) had mutations only detected in the plasma.
Session topic: 13. Myeloma and other monoclonal gammopathies – Biology & Translational Research
Keyword(s): Multiple Myeloma, mutation analysis, Ras