Table 1.
Screening for NF2 mutations in blood and tumors from 19 unrelated patients with NF2 and 1 patient with no clearly established diagnosis
| Retro/ Prospective cohort |
Classification | Patient | Samples: Type Location | Mutational Events | ||||
|---|---|---|---|---|---|---|---|---|
| 1st Mutational Event | 2nd Mutational Event | |||||||
| Genomic DNA Level (NF2) | Copy Number Variation | Genomic DNA Level (NF2) | ||||||
| LZTR1 | SMARCB1 | NF2 | ||||||
| P | 1 | NF2 00435 | Blood | c.[168_174delCCGAGAAinsGGCAC;223_232dup] (5%) | □ | □ | □ | |
| Foot schwannoma (frozen) | c.[168_174delCCGAGAAinsGGCAC;223_232dup] | ■ | ■ | ■ | - | |||
| R | 1 | NF2 00533 | Blood | c.193C>T (2%) | □ | □ | □ | |
| Right vestibular schwannoma (frozen) | c.193C>T, r.115_240del = p.Met39_Lys80del | □ | □ | □ | Copy-neutral LOH (LZTR1 + SMARCB1 + NF2) | |||
| P | 1 | NF2 00075 | Blood | c.241-9A>G, p.Val81fs (15%) | □ | □ | □ | |
| Vestibular schwannoma (frozen) | c.241-9A>G, r.240_241insTTCTGTAG, p.Val81fs | □ | □ | □ | Copy-neutral LOH (at least on SMARCB1 + NF2) | |||
| P | 1 | NF2 00181 | Blood | c.364-103_447 + 2431del2618 (deletion exon 4) (<10%) identified by allele-specific PCR | □ | □ | □ | |
| Medullary ependymoma (FFPE) | c.364-103_447 + 2431del2618 (deletion exon 4) | □ | ■ | ■ | - | |||
| Cervico-dorsal ependymoma (FFPE) | c.364-103_447 + 2431del2618 (deletion exon 4) | ■ | ■ | ■ | - | |||
| P | 1 | NF2 00283 | Blood | c.364-2556_c.447 + 3395del6035 (deletion exon 4) (<10%) identified by allele-specific PCR | □ | □ | □ | |
| Meningioma (frozen) | c.364-2556_c.447 + 3395del6035 (deletion exon 4) | □ | ■ | ■ | - | |||
| P | 1 | NF2 00051* | Blood | c.490delG, p.(Ala164Profs*10) (1,4%) | □ | □ | □ | |
| Schwannoma (frozen) | c.490delG, p.(Ala164Profs*10) | ■ | ■ | ■ | - | |||
| P | 1 | NF2 00294 | Blood | c.493C>T = p.Gln165* (2%) | □ | □ | □ | |
| Meningioma (frozen) | c.493C>T = p.Gln165* | ■ | ■ | ■ | - | |||
| R | 1 | NF2 00522 | Blood | c.586C>T, p.Arg196* (1%) | □ | □ | □ | |
| Vestibular schwannoma (frozen) | c.586C>T, r.586C>T, p.Arg196* | ■ | ■ | ■ | - | |||
| R | 1 | NF2 00531 | Blood | c.592C>T, p.Arg198* (<1%)* | □ | □ | □ | |
| Left vestibular schwannoma (frozen) | c.592C>T, p.Arg198* | □ | □ | □ | Copy-neutral LOH (at least on NF2) | |||
| P | 1 | NF2 00287 | Blood | c.885 + 1221_1575-1182dup13971 (duplication exons 10 to 14) (<10%) identified by allele specific PCR | □ | □ | □ | |
| Left vestibular schwannoma (frozen) | c.885 + 1221_1575-1182dup13971 | ■ | ■ | ■ | - | |||
| P | 2 | NF2 00174 | Blood | Not detected | □ | □ | □ | |
| Jugal cells | c.361C>T, p.(Gln121*) (2%) | □ | □ | □ | ||||
| Right parietal meningioma (FFPE) | c.361C>T, p.(Gln121*) | ■ | ■ | ■ | - | |||
| P | 2 | NF2 00317 | Blood | Not detected | □ | □ | □ | |
| Right forearm schwannoma (FFPE) | c.343C>T, p.(Gln115*) | ■ | ■ | ■ | - | |||
| Dorsal schwannoma (FFPE) | c.343C>T, p.(Gln115*) | ■ | ■ | ■ | - | |||
| P | 2 | NF2 00189 | Blood | Not detected | □ | □ | □ | |
| Left temporal meningioma (FFPE) | c.592C>T, p.Arg198* | ■ | ■ | ■ | - | |||
| Vestibular schwannoma (FFPE) | c.592C>T, p.Arg198* | □ | □ | □ | c.483_484delAT, p.(Leu163Glyfs*39) | |||
| Meningioma 2 (frozen) | c.592C>T, p.Arg198* | ■ | ■ | ■ | - | |||
| Meningioma 3 (frozen) | c.592C>T, p.Arg198* | ■ | ■ | ■ | - | |||
| P | 2 | NF2 00069 | Blood | Not detected | □ | □ | □ | |
| Tentorium cerebelli meningioma (FFPE) | c.784C>T, p.(Arg262*) | ■ | ■ | ■ | - | |||
| Petrous apex meningioma (FFPE) | c.784C>T, p.(Arg262*) | ■ | ■ | ■ | - | |||
| R | 3 | NF2 00524 | Blood | Not detected | □ | □ | □ | |
| Right vestibular schwannoma (frozen) | c.1447-?_1788+?del, p.? (deletion exons 14 to 17) | □ | □ | □ | Copy-neutral LOH (LZTR1 + SMARCB1 + NF2) | |||
| Jugal cells | Not detected | □ | □ | □ | ||||
| R | 3 | NF2 00527 | Blood | Not detected | □ | □ | □ | |
| Vestibular schwannoma (frozen) | c.114 + 3A>T, r.114_115ins56, p.Glu38_Met39insValThrGlyArfgGlnProArgLeuLeuArg* | ■ | ■ | ■ | - | |||
| R | 3 | NF2 00520 | Blood | Not detected | □ | □ | □ | |
| Meningioma (frozen) | c.448+?_1574-?del (deletion exons 5 to 14) | ■ | ■ | ■ | - | |||
| R | 3 | NF2 00536 | Blood | Not detected | □ | □ | □ | |
| Vestibular schwannoma (frozen) | c.1447-?_1788+?del, p.? (deletion exon 7) | ■ | ■ | ■ | - | |||
| R | 3 | NF2 00439 | Blood | Not detected | □ | □ | □ | |
| Vestibular schwannoma (frozen) | c.169C>T, p.Arg57* | □ | □ | □ | c.218_219insT, p.Trp74Leufs*12 | |||
| R | 3 | NF2 00229 | Blood | Not detected | □ | □ | □ | |
| Vestibular schwannoma (frozen) | c.459C>G, p.(Tyr153*) | ■ | ■ | ■ | - | |||
Ten patients showed constitutional NF2 mutation in blood. The NF2 mutation was also found in all matched tumors, together with a second somatic hit (class 1). Four patients did not harbor any NF2 hit in the blood, but mosaicism was identified based on detection of the same variant in 2 independent tumors, or in 1 tumor and another tissue from the same patient (class 2). In 6 patients, only 1 tumor was investigated; all tumors showed 2 NF2 hits but no NF2 mutations were detected in blood (class 3). Germline VAFs are indicated for nontumoral tissues. P, R = prospective or retrospective study; * = patient with no clearly established diagnosis; white square = 2 copies were present for te analyzed loci; black square = only 1 copy was present; gray square = NGS result was not interpretable. - = no point (likely) pathogenic variant detected in the coding regions of NF2, SMARCB1, and LZTR1.