Table 4.

Genes with CR-APA specific to the SI-NETs.

Gene	Function	Role in cancer	APA compared	Functional consequence
DCC	Receptor for the axon guidance molecule nextrin	Tumor suppressor (34)	Increased usage of a proximal polyA site located in intron 5	Usage of this polyA site leads to expression of an mRNA lacking 24 exons in the 3′end, which translates into a highly C-terminally truncated DCC protein containing only 5 Ig-like domains and lacking both the nextrin binding domain, the transmembrane domain, and the intracellular domain. Thus, it lacks the parts responsible for the tumor suppressive functions (34)
PDZD2	PDZ domain-containing protein	Can be cleaved near its C-terminus to generate a secreted form sPDZD2 with tumor suppressive function (35, 36)	Increased usage of two proximal polyA sites located in intron 2	Usage of these polyA sites leads to expression of an mRNA lacking 23 exons in the 3′end, which translates a highly C-terminally truncated PDZD2 protein, lacking the ability to form sPDZD2 and thus the tumor suppressive function (35)
MAGI1	Scaffolding protein localized at cell–cell contacts, containing PDZ domains	Tumor suppressive and anti-metastatic, through β-catenin recruitment to the cell membrane and thus inhibition of the Wnt/β-catenin signaling pathway (37)	Increased usage of two proximal intronic polyA sites located in the intron 2	Usage of these polyA sites leads to expression of an mRNA lacking 21 exons in the 3′end, which translates a highly C-terminally truncated MAGI1 protein, lacking all PDZ domains and thus the tumor suppressive function (37)
ZCWPW2	Zinc finger protein	Unknown	Increased usage of a proximal polyA site located in intron 5	Usage of this polyA site leads to expression of an mRNA lacking five exons in the 3′end, which translates into a highly C-terminally truncated ZCWPW2 protein
LRRFIP1	Transcriptional repressor	Overexpressed in cancer cell lines (38) and pro-metastatic (39)	Increased usage of a proximal polyA site located in the fifth last intron	Usage of this polyA site leads to the expression of an mRNA lacking five exons in the 3′end. The 3′-end of this mRNA isoform corresponds to the 3′-end of the 4.2-kB mRNA overexpressed in cancer cell lines (38)
RIC3	Chaperone protein	Unknown	Increased usage of a proximal intronic polyA site located in intron 1	Usage of this polyA site leads to the expression of an mRNA lacking five exons in the 3′end, giving rise to C-terminally truncated RIC3 protein
THADA	Unknown	Frequently truncated in thyroid adenomas and the truncated allele is hypothesized to play a role in the thyroid tumorigenesis (40)	Increased usage of a proximal polyA site located in the intron 22	Usage of this polyA site leads to the expression of an mRNA lacking 16 exons in the 3′end, i.e., more than in the thyroid adenomas (40), which translates into highly C-terminally truncated THADA protein