PT  - JOURNAL ARTICLE
AU  - Kuan-Ting Lin
AU  - Wai-Kit Ma
AU  - Juergen Scharner
AU  - Yun-Ru Liu
AU  - Adrian R. Krainer
TI  - A human-specific switch of alternatively spliced <em>AFMID</em> isoforms contributes to <em>TP53</em> mutations and tumor recurrence in hepatocellular carcinoma
AID  - 10.1101/169029
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 169029
4099  - http://biorxiv.org/content/early/2017/07/26/169029.short
4100  - http://biorxiv.org/content/early/2017/07/26/169029.full
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.