Alternative splicing of DNA damage response genes and gastrointestinal cancers

Table 1 List of alternatively spliced genes in gastrointestinal cancers

Genes	Role in DDR	Gastrointestinal Cancers	Reference papers
DDR-related genes in gastrointestinal cancers
ATM	DNA damage response kinase involved in HR pathway of DNA repair	Colon cancer cells	[18]
MSH2, MLH1, MHS6, PMS2	Involved in DNA mismatch repair	Colorectal cancer and gastric cancers	[37-39,44,45,57]
MRE11	Component of DNA damage sensor complex MRN	Colorectal cancer	[36]
PARP-1	Involved in single stranded DNA damage repair	Gastric cancer	[63]
	Plays role in controlling HR pathway
RNF43	Function as a regulator of ATM/ATR/DNA damage response	Pancreatic cancer	[46]
		Gastric cancer	[47]
		Sessile serrated adenomas	[48]
AP4	Activation by cellular stresses result in DNA damage inducer of EMT	Mediates EMT in colorectal cancer lines cancer	[84,85]
BRCA1	Involved in HR	Colorectal cancer	[65]
BRCA2	Involved in HR	Pancreatic cancer	[66,67]
U2AF65	With biotinylated triplex DNA affinity	Colorectal cancer	[61]
FIR (PUF60)	Originally a transcriptional facor, also reported as a molecular	Colorectal cancer	[40,96,97]
	sensor for bleomycin-induced DNA damage pathway	Hepatocellular carcinoma	[9]
Other genes in gastrointestinal cancers
P53	Tumor suppressor, guardian of the genome	Colon cancer, head and neck cancer	[10]
CD44	Class I transmembrane glycoprotein involved in cell adhesion, cell-cell	Intestinal tumorigenesis	[41]
	interactions, migration and important player in stem cells and cancer
OPN-b	Osteopontin splice variant, contributed to gastric cancer cell survival	Gastric cancer	[71]
	by regulation of Bcl-2 family proteins and CD44v expressions
p27 (CDKN1B)	Cell cycle regulatory gene	Small intestine neuroendocrine tumors	[72]
c-KIT	Stem cell growth factor receptor, also known as CD117	Gastrointestinal stromal tumors	[75]
Prrx1	Paired related homoeobox 1, a newly reported EMT inducer	Pancreatic cancer	[94]
		Colorectal cancer	[95]
HDM2	Human double minute 2, negative regulator of p53	Colorectal cancer	[79]
PKM2	Pyruvate kinase M2 gene, inactive state is associated with tumor cell proliferation, could switch between PKM2 to PKM1	Impaired colorectal cancer growth	[82]
BRAF	Raf kinase family member BRAF is a proto-oncogen replays a role in	Malignant melanomas	[77]
	regulating the MAP kinase/ERKs signaling pathway	Colorectal cancer
BMP	Bone morphogenetic proteins, are a group of growth factors, function in the formation of bone and cartilage,constitute morphogenetic signals etc.	Gastric cancer	[42]
PRPF6	Pre-mRNA processing factor 6, a member of the tri-snRNP spliceosome complex	Colon cancer	[34,35]
Dystrophin	Cause of Duchenne muscular dystrophy	Metastatic GIST	[76]
FGFR2	The fibroblast growth factor receptor 2, encodes for a fibroblast	Pancreatic ductal adenocarcinoma	[91]
	growth factor-activated transmembrane receptor tyrosine kinase	Hepatic cancer metastasis
Splicing factors in other cancers
SRSF6	Splicing facor	Lung and colon cancers	[26]
hnRNP	Splicing facor	Glioblastoma	[27,28]
SF3B1, U2AF1	Splicing factors	Associated with numerous malignancies	[29-33]
ZRSR2, SRSF2
Ik11 (Ikaros)	Alternative splicing variant of Ikaros, a member of Ikaros family genes	B-cell lympho-proliferative disorders	[24]
Helios	A member of Ikaros family genes	T-cell leukemia	[25]
PUF60 (FIR)	FIR lacks exon5 of PUF60. FIR/PUF60 interacts with SF3B1	Colon cancer, leukemia	[40,80,97]
hnRNPM	RNA-binding protein heterogeneous nuclear ribonucleoprotein M	Breast cancer metastasis	[92]

HR: Homologous recombination; DDR: DNA damage response; EMT: Epithelial-mesenchymal transition; GIST: Gastrointestinal stromal tumors.