AML multi-gene panel testing: A review and comparison of two gene panels

作者：Thakral G^*; Vierkoetter K; Namiki S; Lawicki S; Fernandez X; Ige K; kawahara W; Lum C

来源：Pathology Research and Practice, 2016, 212(5): 372-380.

DOI：10.1016/j.prp.2016.02.004

• AML
• Gene panel
• Screening
• Next-generation sequencing
• Detection
• Prognosis

Background/objective: Risk adapted therapy is standard practice in Acute Myeloid Leukemia (AML). A common diagnostic approach involves focusing on a three gene panel (CEPBA, FLT3, and NPM1). However, a complete representation of prognostic and predictive factors in AML necessitates an expanded series of genes, due to the dynamic interactions present between concurrent mutations. Hence, the current study aims to describe the benefits of an expanded risk profile in an unselected cohort of AML cases.
Methods: The genomes of 11 randomly selected patients with AML were sequenced using next generation sequencing. A narrow three gene panel and broader 50 gene panel were contrasted.
Results: The expanded gene panel detected one additional pathogenic mutation in five patients and two pathogenic mutations in two patients, resulting in a change in their risk profile. Only 5/11 (45%) of AML patients demonstrated a pathogenic mutation on the 3 gene profile, however all patients had at least one detectable pathogenic mutation on the broader gene panel. The detection of a concurrent mutation by the expanded gene panel reversed the favorable risk profile for three patients.
Conclusions: Detection of concurrent mutations enables rejection or validation of prognoses associated with NPM1 or CEBPA mutations. DNMT3a and TP53 mutations in AML have a pertinent prognostic and therapeutic value for patients and their addition enhances the current three gene panel. In our small study, the three gene panel changed the prognosis for three patients (3/11, 27%) with the detection of commonly occurring AML mutations.

• 出版日期2016