Alternate splicing produces a novel cyclin D1 transcript.
Using Northern blotting and PCR analysis of cDNA derived from a range of cell lines and tissues, alternate splicing of the cyclin D1 gene (CCND1) mRNA has been demonstrated. The variant transcript shows no splicing at the downstream exon 4 boundary, encoding a protein with an altered carboxy-terminal domain. Investigation of mRNA extracted from mononuclear cells, lung tumour and normal tissue suggests that both transcripts are invariably expressed. However, splicing to produce the two forms of mRNA is modulated, in the heterozygote, by a frequent A/G polymorphism located within the splice donor region of exon 4. Preliminary analysis of patients with resectable non-small cell lung cancer suggests that genotype is associated with shortened event free survival and greater risk of local relapse.
Betticher
D C
DC
CRC Department of Cancer Genetics, Paterson Institute for Cancer Research, Christie Hospital (NHS) Trust, Manchester, UK.
Thatcher
N
N
Altermatt
H J
HJ
Hoban
P
P
Ryder
W D
WD
Heighway
J
J
D000368:Aged; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001483:Base Sequence; D015152:Blotting, Northern; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism; D019938:Cyclin D1; D016213:Cyclins / Q000235:genetics*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D015513:Oncogene Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000032:analysis*
D016213:Cyclins; D015513:Oncogene Proteins; D012333:RNA, Messenger; D019938:Cyclin D1