48. Identification of a novel CEBPA homozygous duplication by NGS and SNP microarray

Abstract

The prognostic significance of CEBPA variants in acute myeloid leukemia (AML) is less favorable for individuals with a single CEBPA variant compared to individuals with biallelic CEBPA variants at the N- and C-termini of the protein. Few AML cases with homozygous CEBPA variants have been reported, and a better understanding of such cases could aid determination of prognostic impact of these variants. Here, we report a patient with newly diagnosed AML that was negative by outside testing for both the FLT3 internal tandem duplication (FLT3-ITD) and tyrosine kinase domain mutations. Cytogenetic testing showed a bone marrow karyotype of 46,XY[20] and FISH results were within normal limits for AML-related abnormalities. Next generation sequencing analysis revealed an NRAS pathogenic variant (LRG_92t1:c.38G>T, p.(Gly13Val)), three GATA2 variants of clinical significance/possible clinical significance (LRG_295t2:c.1085G>A, p.(Arg362Gln)(;)1018-14_1036dup, p.(?)(;)989G>C, p.(Arg330Pro)), and a C-terminal in-frame duplication of 30 nucleotides in the CEBPA gene (LRG_456t1:c. c.950_979dup, p.(Leu317_Lys326dup)). Wild-type sequence was not detected in the region surrounding the CEBPA variant and a SNP chromosomal microarray revealed loss of heterozygosity spanning 19q13.11-19q13.43, which includes the CEBPA gene (arr[GRCh37] 19q13.11q13.43(33,365,429-59,097,752) hmz). Together, these NGS and microarray results are consistent with a homozygous CEBPA duplication. Although homozygous CEBPA variants are rare in AML, they have a similar gene expression signature to AML with biallelic CEBPA variants. While it remains to be determined if the prognosis for AML patients with these variants is similar to AML patients with biallelic CEBPA variants, these results may aid prognostic studies in the future.