Table 1 WGS refined diagnoses
Case | Pre-WGS diagnosis | Selected key diagnostic drivers | Post-WGS integrated diagnosis |
|---|---|---|---|
1 | Recurrent Wilm’s tumour vs undifferentiated sarcoma (radiation-related) | HomDels of ATRX, RAD51 Absence of typical WT drivers [41] | Undifferentiated sarcoma |
4 | Favour dedifferentiated gastrointestinal stromal tumour (GIST) (DOG1+) | 4q Amplification (KIT/NRAS/PDGFRA) and MDM2 amplification Absence of typical GIST drivers [42] | Favour undifferentiated sarcoma |
5 | Leiomyosarcoma | Amplification of MDM2/CDK4 and JUN [43] | Dedifferentiated liposarcoma |
7 | Cellular schwannoma vs malignant peripheral nerve sheath tumour (MPNST) | SOX10 Indel [44] | Cellular schwannoma |
9 | Malignant meningioma | YAP1::KMT2A fusion [47] | KMT2A-rearranged sarcoma |
11 | Recurrent metaplastic breast carcinoma vs undifferentiated sarcoma | 4q Amplification (KIT/NRAS/PDGFRA) [25] + novel TP53 mutation Absence of TP53 mutation found in previous primary or other small drivers common in breast carcinoma | Undifferentiated sarcoma |
14 | Low-grade mesenchymal soft tissue neoplasm, favouring plexiform fibromyxoma | GLI1-altered soft-tissue tumour | |
16 | Poorly differentiated carcinoma of unknown primary vs undifferentiated sarcoma | Truncating NF2 mutation + haploidisation [12] | Peritoneal mesothelioma |
17 | High-grade bone sarcoma with suspected BCOR alteration (by IHC) | TP53 exon 1 truncating mutation [13] + amplifications in 4q/MYOCD/RICTOR/COPS3 [50] Wild-type BCOR locus | Osteosarcoma |
18 | Metastatic sex cord-stromal tumour vs endometrial stromal sarcoma | JAZF1::SUZ12 | Low-grade endometrial stromal sarcoma |
24 | Hamartomatous vascular malformation | PIK3CA mutation [51] | PIK3CA mutated vascular neoplasm |
27 | MPNST vs undifferentiated pleomorphic sarcoma (UPS) in a patient with NF1 | CCNE1 gain, PTEN disruption Absence of variants typical of MPNST [46] | UPS |
30 | Benign fibrous histiocytoma vs plexiform fibrohistiocytic tumour | No drivers identified [52] | Favour a plexiform fibrohistiocytic tumour |
32 | MPNST vs cellular schwannoma | Isolated NF2 disruptive insertion + LOH [53] Absence of typical MPNST-associated SNVs | Cellular schwannoma |
36 | Cutaneous spindle cell neoplasm of uncertain type | PDPN::PRKCB [54] | Benign fibrous histiocytoma (cellular variant) |
37 | Metastatic sarcomatoid prostate cancer vs radiation-induced sarcoma | TMPRSS2::ERG fusion + KMT2C disruptive SV [55] | Prostate carcinoma |
45 | Recurrent Wilm’s vs primary carcinoma/round cell sarcoma | ASXL1/MYCN/NONO/FBXW7/AMER1/1q gain [41] | Recurrent Wilm’s tumour |
48 | Recurrent rhabdomyosarcoma vs melanoma vs NET | EWSR1::ATF1 [56] | Malignant neuroectodermal gastrointestinal tumour |
49 | Angiomyxoma vs cellular angiofibroma | Segmental copy number alterations | Unclassified sarcoma |
53 | Spindle cell tumour infiltrating ganglia vs ganglioneuroma | Absence of any genomic changes | Ganglioneuroma |
54 | Sarcoma (NOS) favouring dedifferentiated liposarcoma | Alterations in PHF6 | Unclassified sarcoma |
60 | Vascular neoplasm, favouring angiosarcoma | WWTR1::CAMTA1 fusion | Epithelioid haemangioendothelioma |
65 | UPS | TPR::NTRK1 fusion [59] | NTRK-rearranged mesenchymal neoplasm |
66 | Carcinoma of unknown primary | TP53 intron 1 disruptive SV [13] | Osteosarcoma |
67 | Sarcoma (NOS) | EWSR1::FEV1 fusion [11] IDH1 mutation | EWSR1::FEV1 rearranged soft-tissue tumour |
