Table 3.
Genetic alterations in ATRX-negative APT and PC by panel NGS
| Pt. | Specimen | Local. | ATRX expression | Genes | Coding | Amino Acid | Freq. (%)# |
|---|---|---|---|---|---|---|---|
| 1 | Cushing/PC | Pituitary | loss | ATRX | c.134_6217del | p.D45-K2027del | Nu |
| 2 | Cushing/PC | Pituitary | loss | ATRX | c.748C>T | p.Arg250Ter | 89 |
| Lynch sy | TP53 | c.524G>A | p.Arg175His | 84 | |||
| PTEN | c.697C>T | p.Arg233Ter | 10 | ||||
| 3 | Lactotroph/APT | Pituitary | loss | ATRX | c.21_6699del | p.E8-K2233del | Nu |
| TP53 | c.584T>A | p.Ile195Asn | 92 | ||||
| RB1 | c.1725_1726 insAACAA | p.Ser576fs | 13 | ||||
| RB1 | c.1218_1697del | p.N406-S565del | He | ||||
| 4 | Cushing/PC | Pituitary | loss | ATRX | c.6679delG | p.Asp2227fs | 81 |
| ATRX | c.3583delA | p.Arg1195fs | 12 | ||||
| 5* | Silent ACTH/PC | Pituitary | retained (major)/loss (minor) | ATRX | c.4048_4049delGG | p.Gly1350fs | 28 |
| ATRX | c.6661G>T | p.Glu2221Ter | 31 | ||||
| TP53 | c.644G>A | p.Ser215Asn | 30 | ||||
| 5a | Silent ACTH/PC | Pituitary | loss (major)/retained (minor) | ATRX | c.4048_4049delGG | p.Gly1350fs | 67 |
| ATRX | c.6661G>T | p.Glu2221Ter | 10 | ||||
| TP53 | c.644G>A | p.Ser215Asn | 8 | ||||
| 5 | Silent ACTH/PC | Metastasis | loss | ATRX | c.4048_4049delGG | p.Gly1350fs | 98 |
| 6 | Cushing/APT | Pituitary | loss | ATRX | c.2422C>T | p.Arg808Ter | 72 |
| TP53 | c.1024C>T | p.Arg342Ter | 51 | ||||
| PTEN | c.697C>T | p.Arg233Ter | 55 | ||||
| 7 | Cushing/APT | Pituitary | loss | ATRX | c.839_840insCATG | p.Asn281Ter | 44 |
| TP53 | c.818G>A | p.Arg273His | 85 | ||||
| NF2 | c.1052G>A | p.Arg351His | 20 | ||||
| 8 | Cushing/APT | Pituitary | loss | ATRX | c.5938T>A, c.5939delC | p.Ser1980fs | 88 |
| TP53 | c.375G>A | p.( = ) | 81 | ||||
| 9 | Mixed GH-PRL/PC | Pituitary | loss | ATRX | c.595_6699del | p.N199-K2233del | He |
| CDKN2A | c.1_501del | p.M1-A167del | Ho | ||||
| CDKN2B | c.1_414del | p.M1-D138del | Ho | ||||
| 9 | Mixed GH-PRL/PC | Metastasis | loss | ATRX | c.595_6699del | p.N199-K2233del | He |
| CDKN2A | c.1_501del | p.M1-A167del | Ho | ||||
| CDKN2B | c.1_414del | p.M1-D138del | Ho |
Abbreviations: APT, aggressive pituitary tumors; PC, pituitary carcinoma; NGS, next-generation sequencing; ACTH, adrenocorticotropic hormone, GH, growth hormone; PRL, prolactin; #, estimated ploidy level of larger gene deletions: Nu: nullizygous, He: hemizygous deletion, Ho: homozygous deletion.
a The same mutations were detected in ATRX immunopositive and immunonegative tissue fractions indicating that they could not be successfully separated.