Table 1.
Genomic sequencing studies for most common genetic alterations in human MPNST. All MPNST or neurofibromas in study reported under n. Reported sequencing results given as in reference (cases or percentages) for human MPNST specimens.
| Ref. | Study Author Year |
Description |
n Total MPNST (n NF1 Associated) n (Other Specimen Types) |
NF1 | CDKN2A | TP53 | EED | SUZ12 | Notes |
|---|---|---|---|---|---|---|---|---|---|
| [38] | Mantripragada, 2008 | Targeted seq, aCGH | 35 (35) 16 pNF 8 cNF |
71% | 39% | 17% | NR | NR | |
| [39] | Verdijk, 2010 | Targeted seq | 88 (26) | NR | ND | 17/72 | ND | ND | 36% of TP53 mutations detected were from NF1 patients |
| [40] | Yang, 2011 | aCGH | 51 (16) | ~30% | 65% | ~30% | NR | NR | |
| [41] | DeRaedt, 2014 | Targeted seq, aCGH | 51 (51) | 51/51 | NR | NR | 15/51 | 32/51 | |
| [42] | Zhang, 2014 | WGS (5), WES (3), Targeted seq (42) |
50 (39) 11 (paired neurofibroma) |
22/50 | 1/8 | 1/8 | 1/50 | 16/50 | |
| [43] | Lee, 2014 | WES (15), SNP, targeted (37) | 52 (27) 7 neurofibromas |
45/52 | 42/52 | 23/52 | 19/52 | 25/52 | RNAseq analysis of MPNST with PRC2 loss vs. intact PRC2 demonstrates enrichment of genes associated with development and morphogenesis |
| [44] | Sohier, 2017 | Exome seq, aCGH | 8 (8) 1 pNF 7 cNF |
8/8 | 5/8 | 1/8 | 2/8 | 7/8 | No TP53 point mutations identified |
| [45] | Brohl, 2017 | WES + SNP | 5 (4) + 7 TCGA cases (6) |
11/12 | 7/12 | 6/12 | 4/12 | 5/12 | 5/12 MPNST contain somatic Ras-pathway activating mutation |
| [46] | Zehir, 2017 | IMPACT NGS | 11 | 2/11 | 6/11 | NR | 1/11 | 2/11 | Data accessible through cBioPortal |
| [47] | Kaplan, 2018 | Foundation Medicine NGS 2014–2016 | 186 (clinical data NR) | 102 of 186 | 57% overall (71% NF1-altered, 80% BRAF altered, 34% non-NF1/non-BRAF altered) |
32% of NF1 14% of non-NF1 |
8% of NF1-altered, 13% of BRAF-altered, 3% of non–NF1/non–BRAF-altered |
20% of NF1-altered, 13% of BRAF-altered, 9% of non–NF1/non–BRAF-altered |
Data reported as % of NF1/BRAF cohorts rather than absolute numbers |
| [48] | Pemov, 2019 | NF1 deep sequencing (4); WES (3); CNV (28) | 31 (4) 16 ANF |
4/4; 10/28 (Loss, CNV) | 4/4; 20/28 (Loss, CNV) |
0/3 (WES); 10/28 (Loss, CNV) | 1/3 (WES); 10/28 (Loss, CNV) |
1/3 (WES); 9/28 (Loss, CNV) |
RNAseq reported for ANF and 4 MPNST |
| [49] | Pollard, 2020 | WES | 1 (1) 7 pNF 13 cNF |
1 | 0/1 | 0/1 | 0/1 | 1/1 | RNAseq on cNF, pNF, and MPNST samples from 23 patients |
aCGH = array comparative genomic hybridization; WGS = whole genome sequencing; WES = whole exome sequencing; SNP = single nucleotide polymorphism; NGS = next generation sequencing; CNV = copy number variation; NR = not reported; ND = not determined; cNF = cutaneous neurofibroma; pNF = plexiform neurofibroma; ANF = atypical neurofibroma.