Table 1.

G Protein-Coupled Peptide Hormone Receptor Splice Variants in Tumors

Receptor	Transcript	Protein	Function	Tumoral expression	In vivo targeting
CCK2 receptor	Intron 4 retention	69 aa insertion in IC3	Constitutive activity; stimulation of proliferation	Insulinomas, gastrointestinal stromal tumors, colorectal adenomas and adenocarcinomas, pancreatic and gastric adenocarcinomas, Barrett’s mucosa, small and non-small cell lung cancer	Antisense oligonucleotide inhibits growth of pancreatic cancer xenografts in nude mice; 90in vivo tumor binding of radiolabeled ligand in animal model
Secretin receptor	Exon 3 skipping	36 aa deletion in N-terminus	No ligand binding, dominant negative activity on wild-type. Inhibition of gastrin secretion from gastrinomas?	Gastrinomas, pancreatic adenocarcinomas, cholangiocellular carcinomas
	Exons 3 + 4 skipping	No TMs	No ligand binding, secreted	Pancreatic adenocarcinomas, cholangiocellular carcinomas	Detectable in pancreatic cancer and chronic pancreatitis patients’ sera with ELISA
	Exons 2 + 3 skipping	No TMs	No ligand binding	Lung carcinoids
	Exon 9 skipping	Truncation in IC2	No signaling	Lung carcinoids
GHRH receptor	Exons 1-3 skipping, intron 3 retention (SV1)	N-terminal truncation	Constitutive activity; stimulation of proliferation	Prostate, breast, endometrial, ovarian, pancreatic, colorectal, gastric, esophageal, and small cell lung cancer, adrenal cortical carcinomas, insulinomas, gastrinomas, pituitary adenomas, glioblastomas, malignant melanomas, lymphomas	Antagonists inhibit growth of tumor xenografts in nude mice
	Exons 1-3 and 7 skipping, intron 3 retention (SV2)	N-terminal truncation, truncation after EC1		Prostate, breast, ovarian, and pancreatic cancer
	Exons 1-3 and 5–7 skipping, intron 3 retention (SV4)	N-terminal truncation, no TMs		Pituitary adenomas
	Exon 11 skipping	Truncation after IC3	No signaling; dominant negative activity on wild-type	Pituitary adenomas
PAC1 receptor	Variable skipping of exons 4-6 and 13-16	Deletions in N-terminus and IC3	Variable ligand binding affinity and stimulation of intracellular signal transduction	Neuroblastomas, retinoblastomas, colorectal carcinomas
VPAC1 receptor	Exons 10 + 11 skipping	Deletion of part of TM5, IC3, TM6, EC3, and TM7	No signaling	B and T cell lymphomas, colorectal carcinomas
VPAC2 receptor	Exons 10 + 11 skipping	Deletion of part of TM5, IC3, TM6, EC3, and part of TM7	No signaling	T cell leukemia
LH/hCG receptor	Exon 9 skipping	62 aa deletion in N-terminus	No ligand binding, no cell surface expression, complexing with and degradation of wild-type LH/hCG and FSH receptors in endoplasmic reticulum	Endometrial and ovarian adenocarcinoma
	Exon 9 skipping, intron 10 retention89	No TMs		Ovarian adenocarcinoma
Corticotropin releasing factor receptor 1	Intron retention	29 aa insertion in IC191		Pituitary adenoma

aa, amino acids; EC, extracellular loop; IC, intracellular loop; TM, transmembrane segment.