RT Journal Article
SR Electronic
T1 A human-specific switch of alternatively spliced <em>AFMID</em> isoforms contributes to <em>TP53</em> mutations and tumor recurrence in hepatocellular carcinoma
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 169029
DO 10.1101/169029
A1 Kuan-Ting Lin
A1 Wai-Kit Ma
A1 Juergen Scharner
A1 Yun-Ru Liu
A1 Adrian R. Krainer
YR 2017
UL http://biorxiv.org/content/early/2017/07/26/169029.abstract
AB Pre-mRNA splicing can contribute to the switch of cell identity that occurs in carcinogenesis. Here we analyze a large collection of RNA-Seq datasets and report that splicing changes in hepatocyte-specific enzymes, such as AFMID and KHK, are associated with HCC patients’ survival and relapse. The switch of AFMID isoforms is an early event in HCC development, and is associated with driver mutations in TP53 and ARID1A. Finally, we show that the switch of AFMID isoforms is human-specific and not detectable in other species, including primates. The integrative analysis uncovers a mechanistic link between splicing switches, de novo NAD+ biosynthesis, driver mutations, and HCC recurrence.