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] Absence of typical MPNST/eMPNST drivers [45, 46]	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	ACTB::GLI1 fusion [48, 49]	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 Absence of alterations of HMGA2 and RB1 [57, 58]	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