Effective requesting method to detect fusion transcripts in chronic myelomonocytic leukemia RNA-seq
RNA sequencing technology combining short read and long read analysis can be used to detect chimeric RNAs in malignant cells. We propose here an integrated approach that uses k-mers to analyze indexed datasets. This approach is used to identify chimeric RNA in chronic myelomonocytic leukemia (CMML) cells, a myeloid malignancy that associates features of myelodysplastic and myeloproliferative neoplasms. In virtually every CMML patient, new generation sequencing identifies one or several somatic driver mutations that typically affect epigenetic, splicing and signaling genes. In contrast, cytogenetic aberrations are currently detected in only one third of the cases. Chromosomal abnormalities nevertheless contribute to patient stratification, some of them being associated with higher risk of poor outcome, e.g. through disease transformation into acute myeloid leukemia (AML). Our approach selects four chimeric RNAs detected and validated in CMML cells. We further focus on NRIP1-MIR99AHG, as this fusion was also recently detected in AML cells. We show that this fusion encode three isoforms, including a novel one. Further studies will decipher the biological importance of such a fusion and its potential to improve disease stratification. Together, this report demonstrates the ability of a large-scale approach to detect chimeric RNAs in cancer cells.