Table 1. enomic portfolio in each of 17 patients with Merkel cell carcinoma [a].
| C | Aberrations | No. of genealterations per patient [a] | Cell cycle pathway | DNA repair gene | PI3K/AKT/mTORpathway | Potentially actionable |
|---|---|---|---|---|---|---|
| 1 | NF1 L937* | 3 | X | Yes | ||
| RB1 Q685* | X | No | ||||
| TP53 H179Y | Yes | |||||
| 2 | RICTOR amplification | 1 | X | Yes | ||
| 3 | CDKN2C loss | 2 | X | Not clear | ||
| PIK3R1 Q221* | X | Yes | ||||
| 4 | BAP1 G422fs*8 | 5 | X | Yes | ||
| BRCA2 K3326* | X | Yes | ||||
| PDGFRB L986F [b] | Yes | |||||
| RB1 Q257* | X | No | ||||
| TP53 C275W | Yes | |||||
| 5 | ARID1A loss | 1 | No | |||
| 6 | MYC amplification | 4 | No | |||
| NTRK3 K461R [b] | Yes | |||||
| RB1 Q93* | X | No | ||||
| TP53 K120* | Yes | |||||
| 7 | AKT2 amplification | 3 | X | Yes | ||
| RB1 Q93* | X | No | ||||
| TP53 Q331* | Yes | |||||
| 8 | CDKN2A/B loss | 2 | X | Yes | ||
| EGFR E282K [b] | Yes | |||||
| 9 | BAP1 Q729* | 5 | X | Yes | ||
| FANCA T1161M [b] | X | Yes | ||||
| MLH1 E694* | X | Yes | ||||
| RB1 splice site 1499 − 2A > G RB1 splice site 2489 + 1G > A TP53 R248W |
X X |
No No Yes |
||||
| 10 | FBXW7 Q95* | 5 | X | Yes | ||
| NOTCH1 splice site 4586 + 1G > A [c] | X | Yes | ||||
| RB1 splice site 1422 − 1G > A | No | |||||
| SMARCA4 R1192C | No | |||||
| TP53 R280K | Yes | |||||
| 11 | KMT2D truncation, exon 4 | 4 | Not clear | |||
| NOTCH1 splice site 5168 − 1G > A [c] | Yes | |||||
| RB1 A392fs*5 | X | No | ||||
| TP53 R175H | Yes | |||||
| 12 | ATM R2993* | 4 | X | Yes | ||
| NOTCH1 E256* [c] | Yes | |||||
| RB1 S249* | X | No | ||||
| TP53 R282W | Yes | |||||
| 13 | BRCA1 Q1756* | 4 | X | Yes | ||
| PIK3CA E542K | X | Yes | ||||
| PTEN splice site 635 − 1G > A | X | Yes | ||||
| TP53 E339K | Yes | |||||
| TP53 G187S | Yes | |||||
| TP53 R202fs*45 | Yes | |||||
| 14 | ALK F1174CRET E511K | 2 | YesYes | |||
| 15 | CHEK2 R346G [b] | 3 | X | Yes | ||
| PIK3CA R88Q | X | Yes | ||||
| TP53 P177L | Yes | |||||
| 16 | PIK3CA G1049R | 4 | X | Yes | ||
| PTCH1 P369L [b] | Yes | |||||
| RB1 M386fs*1 | X | No | ||||
| TP53 R224H | Yes | |||||
| TP53 Y220* | Yes | |||||
| 17 | APC W2612* | 5 | Yes | |||
| EPHAS R417Q [b] | Not clear | |||||
| NF1 splice site 5609 + 1G > A | X | Yes | ||||
| RB1 W99* | X | No | ||||
| TP53 P151S | Yes | |||||
| TP53 R248W | Yes |
Abbreviations: C, case; No., number.
[a]
4 cases had more than one molecular aberration in the same gene: case 9 [RB1 = 2], case 13 [TP53 = 3], case 16[TP53 = 2], and case 17 [TP53 = 2].
[b]
Aberration is of uncertain clinical significance and relevance of therapeutic strategies is unknown.
[c]
Aberration is an inactivating alteration and therapeutic strategies are not expected to be relevant.