Abstract 6126
Background
Identification of clinically actionable mutations in cancer is essential for catalyzing precision oncology based on risk stratification. Currently, little is known about the mutation profile of high-risk acute lymphoblastic leukemia (ALL) in Korean patients. We aimed to develop a multigene panel for ALL and to investigate clinically actionable mutations in the Korean patients with high-risk ALL.
Methods
We developed a multigene panel targeting 102 genes with diagnostic, prognostic, or therapeutic significance in ALL and validated it using reference materials and clinical samples. The mutation analyses were done in a total of 18 patients with high-risk ALL {T lymphoblastic leukemia (T-ALL, n = 7), B lymphoblastic leukemia in relapse (relapsed B-ALL, n = 5), and Philadelphia chromosome-positive ALL (Ph+ ALL, n = 6)}. High-risk ALL was categorized based on clinical findings and laboratory tests including immunophenotyping, chromosome analyses, fluorescence in situ hybridization, and RT-PCR. Clinically actionable mutations were selected based on a four-tiered system recommended by Association for Molecular Pathology in 2017.
Results
A total of 28 clinically actionable mutations including 6 novel mutations were identified in 83% of the patients. The most frequent alterations in Korean patients were loss of function mutations of KMT2C (78%), followed by mutations of NOTCH1 (17%) and SUZ12 (11%). There is no difference in the frequency of KMT2C mutation among T-ALL, relapsed B-ALL, and Ph+ ALL, while mutations in NOTCH1 and SUZ12 were observed only in T-ALL. Additional 8 genes including NT5C2 and KRAS were mutated. Furthermore, potential germline pathogenic variants were discovered in 3 patients including one previously diagnosed as neurofibromatosis type 1.
Conclusions
This study showed that KMT2C mutations were recurrently observed in Korean patients with high-risk ALL. The KMT2C mutation status could be an effective risk stratification strategy for Korean patients with ALL. This study provides clinically actionable mutational portrait of high-risk ALL, albeit in a limited number of patients and gives novel insight into genetic heterogeneity of the disease.
Clinical trial identification
Legal entity responsible for the study
Pusan National University Yangsan Hospital Institutional Review Board.
Funding
Biomedical Research Institute in Pusan National University Yangsan Hospital.
Editorial Acknowledgement
Disclosure
All authors have declared no conflicts of interest.