Table 1.
Overview of pathogenic variants and pancreatic cancer occurrence
| Variant location | CDKN2A nucleotide change* | CDKN2A/p16INK4a amino acid change | CDKN2A/p14ARF amino acid change | Total no. of families (no. of proven carriers) |
No. of families with PDAC (no. of proven carriers in these families) |
No. of PDAC cases (no. of validated† cases) |
No. of proven carriers with PDAC + no. of obligate carriers with PDAC |
PDAC occurrence in literature |
| Exon 1β | c.193G>C | None | p.(Gly65Arg) | 4 (8) | 0 (−) | 0 (−) | 0+0 | No |
| Exon 1β | c.193+1G>A | None | p.? (splicing) | 5 (12) | 0 (−) | 0 (−) | 0+0 | No |
| Exon 1α | c.-34G>T | p.? | None | 4 (8) | 0 (−) | 0 (−) | 0+0 | Yes6 7 15 19 37 |
| Exon 1α | c.47T>G | p.(Leu16Arg) | None | 3 (9) | 2 (5) | 2 (0) | 0+1 | Yes15 19 |
| Exon 1α | c.67G>C | p.(Gly23Arg) | None | 9 (55) | 6 (39) | 12 (5) | 5+4 | No |
| Exon 1α | c.71G>C | p.(Arg24Pro) | None | 2 (3) | 2 (3) | 2 (2) | 2+0 | Yes6 7 15 19 37 |
| Exon 1α | c.131-132insAA | p.(Tyr44*) | None | 1 (3) | 0 (−) | 0 (−) | 0+0 | Yes15 19 |
| Exon 1α | c.143C>A | p.(Pro48Gln) | None | 1 (8) | 1 (8) | 3 (1) | 1+1 | Variant not reported |
| Exon 2 | c.151-2A>G | p.? (splicing) | p.? (splicing) | 1 (12) | 1 (12) | 1 (0) | 0+0 | Variant not reported |
| Exon 2 | c.159G>A | p.(Met53Ile) | p.(Asp68Asn) | 2 (5) | 1 (4) | 1 (1) | 0+0 | Yes15 19 |
| Exon 2 | c.203C>T | p.(Ala68Val) | p.(Arg82Arg) | 2 (7) | 0 (−) | 0 (−) | 0+0 | Yes36 |
| Exon 2 | c.225_243del | p.(Ala76Cysfs*64) | p.(Arg90Valfs*76) | 131 (484) | 82 (302) | NA | NA | Yes6–8 10 15 16 19 37 |
| Exon 2 | c.301G>T | p.(Gly101Trp) | p.(Arg115Leu) | 2 (2) | 0 | 0 (−) | 0+0 | Yes6 7 14 15 19 37 |
| Exon 2 | c.352G>A | p.(Ala118Thr) | p.(Gly132Asp) | 4 (31) | 0 | 0 (−) | 0+0 | Variant not reported |
| Exon 1+2+3 | Deletion 155 kb of CDKN2A, CDKN2B and partially MTAP | p.? (whole gene deletion) |
p.? (whole gene deletion) |
1 (2) | 0 | 0 (−) | 0+0 | Variant not reported |
The variants c.143C >A and c.203C >T are located on a pathogenic haplotype.
*RefSeq NM_000077.4 isoform p16INK4a, RefSeq NM_058195.3 isoform p14ARF (for exon 1β).
†Through medical records and/or pathology reports.
CDKN2A, cyclin-dependent kinase inhibitor 2A; NA, not analysed; PDAC, pancreatic ductal adenocarcinoma.