👤 Vincent W Keng

Myeloid/lymphoid neoplasms with FGFR1 rearrangement are a rare group of neoplasms that share features of eosinophilia and lineage promiscuity. First, we described a challenging case of acute leukemia with lineage switch and cytogenetically cryptic FGFR1. Second, we aimed to systemically review this phenomenon in published literature. A 68-year-old man with a history of chemotherapy exposure presented with acute leukemia of myeloid lineage without eosinophilia or 8p11 abnormalities on karyotyping. Over a refractory and relapsing course, the blast phenotype shifted to B lymphoid. Fluorescence in situ hybridization identified a cytogenetically cryptic FGFR1 rearrangement, likely a paracentric inversion. We identified 26 published cases of FGFR1-rearranged acute leukemia with ambiguous, mixed, or switching lineage. Although there was variability in the partner gene, anatomical location of different phenotypes, and timing of lineage switch, the prognosis was consistently poor in the absence of novel therapy. Ours is the only reported case of FGFR1-rearranged neoplasms with a disease sequence of acute myeloid leukemia transforming to B-cell acute lymphoblastic leukemia and 1 of only 3 reported cases with cytogenetically cryptic FGFR1 rearrangement. Fluorescence in situ hybridization testing for FGFR1 rearrangement should be a standard investigation in leukemia of mixed or switching lineage. Show less

A forward genetic Sleeping Beauty (SB) insertional mutagenesis screen, followed by high-throughput transcriptome sequencing, was used to identify driver genes responsible for hepatocellular carcinoma (HCC)-associated metastasis. Using RNA-sequencing (RNA-seq) to identify transposon-endogenous transcriptome fusion genes, the phylogenetic lineage between the parental liver tumor and secondary metastasis can be determined to provide mechanistic insight to genetic changes involved in the metastatic evolution process. In the current study, two novel candidate genes were identified to be potentially involved in HCC-associated metastatic progression, canopy FGF signaling regulator 2 (Cnpy2) and actinin alpha 2 (Actn2). Transposon-Cnpy2 fusion transcripts were identified in both primary liver tumors and lung metastases. Its significant association with clinicopathological characteristics and correlated gene enrichment in metastasis-related mechanisms suggest its potential role in modulating local invasion and angiogenesis. Other known driver genes for human HCC that can also promote metastatic progression include epidermal growth factor receptor (Egfr) and RNA imprinted and accumulated in nucleus (Rian). Metabolic pathway related gene carbamoyl phosphate synthetase (Cps1) was identified to play an important role in early HCC development, while cell junction-related pathway gene Rac family small GTPase 1 (Rac1) was identified to take part in both HCC and pro-metastatic progression. Importantly, actinin alpha 2 (Actn2) was identified exclusively in the secondary metastasis site and its role in HCC-related metastatic process was elucidated using in vitro approaches. ACTN2-overexpression in human liver cancer cells displayed enhanced cellular motility and invasion abilities, indicating its possible function in later stage of metastasis, such as extravasation and lung colonization. Show less