Schematic representation of the genomic organization of the CDKN2A/ ARF -CDKN2B gene cluster on chromosome 9p21.3. CDKN2A and ARF share the same exons 2 and 3 but include different first exons (1α and 1β). The alternative splicing of exon 1α or exon 1β to exons 2 and 3 gives rise to a difference in the reading frames between CDKN2A and ARF, thereby accounting for the absence of any amino acid homology between the proteins encoded by CDKN2A and ARF. The long non-coding RNA ANRIL (antisense non-coding RNA in the INK4 in locus) gene contains 19 exons and is transcribed in the antisense orientation of the CDKN2A/ARF-CDKN2B gene cluster. Black arrows indicate the transcriptional orientation of the genes at 9p21.3. The red arrow indicates the relative position of the SNP rs2151280 within ANRIL intron 3.