Reference set (classifier version: 12.2)

The reference set is highly reminiscent of the WHO classification of brain tumors but not identical. For the constriction of the reference set at least 8 typical cases of each histological subtype described in the WHO classification of brain tumors were collected and underwent critical histological review. If available, only cases at first diagnosis and prior to radiation or chemotherapy were selected. For the majority of cases DNA was extracted from formalin fixed paraffin embedded tumor tissue. A special focus was set on tumor purity with rigorous dissection of areas with maximal tumor cell content.

The cases were then defined as a group for the random forest algorithm (supervised learning algorithm) and tested by cross validation. For cases with repeated misclassification unsupervized clustering was performed with the aim to identify to the DNA methylation core group within the histological group. This led to the splitting of various WHO entities (e.g. PNET with 4 molecular subtypes, subependymoma splitting into supratentorial, posterior fossa and spinal subtype). For other rare WHO entities we were either so far not able to obtain enough cases to incorporate the group into the classifier or there was no indication of a group by unsupervized clustering (e.g. astroblastoma). This is why our reference set strongly resembles the WHO classification but is not identical.
Name Description Details
Methylation class Ewings sarcoma The methylation class Ewings sarcoma" is based on tumours with a histological small blue round cell phenotype. Location is frequently skeletal, but extraskeletal sites may be prevalent; median age is 19 years (age range 3 to 66). Cases of this class consistently carry a gene fusion between TET- and ETS gene family members mostly resulting in a EWSR1-FLI1 fusion gene. A gain of chromosome 8 can be observed in up to 40% of cases. show
Methylation class Kaposi sarcoma The methylation class "Kaposi sarcoma" is based on tumours with the histological diagnosis of Kaposi sarcoma. These tumours are predominantly located in the skin of the lower extremity; median age is 73 years (age range 58 to 77); striking predominance in males. Human herpes virus 8 (HHV-8) is consistently found in cases of this class. Most cases show a flat profile in copy number analysis. show
Methylation class Langerhans cell histiocytosis The methylation class "Langerhans cell histiocytosis" is based on tumours with the histological diagnosis of Langerhans cell histiocytosis. These tumours are mostly located in the bone. Median age is 22 years (age range 3 to 48). Recurrent chromosomal alterations are not observed and most cases show a flat profile in copy number analysis. These tumours frequently carry BRAF V600 mutations (5/11). show
Methylation class alveolar soft part sarcoma The methylation class "alveolar soft part sarcoma" is based on tumours with the histological diagnosis of alveolar soft part sarcoma. Location is the soft tissue in all cases; median age is 15 years (age range 3 to 60). Cases of this class consistently carry a ASPSCR1-TFE1 gene fusion. Most cases show a flat profile in copy number analysis. show
Methylation class angioleiomyoma / myopericytoma The methylation class "angioleiomyoma / myopericytoma" is based on tumours with the histological diagnosis of angioleiomyoma and myopericytoma. Cases of this class most commonly arise in the soft tissue of the limbs; median age is 50 years (age range 25 to 87). Most cases show a flat profile in copy number analysis. show
Methylation class angiomatoid fibrous histiocytoma The methylation class "angiomatoid fibrous histiocytoma" is based on tumours with the histological diagnosis of angiomatoid fibrous histiocytoma. Location is the soft tissue in all cases; median age is 11 years (age range 6 to 13). Cases of this class frequently carry a EWSR1-CREB1 gene fusion and most cases show a flat profile in copy number analysis. show
Methylation class angiosarcoma The methylation class "angiosarcoma" is based on tumours with the histological diagnosis of angiosarcoma. Location is the soft tissue (including skin) most commonly of the radiated mamma (51%), or the skin of the head region (30%); median age is 73 years (age range 38 to 99). The copy number profile shows numerous alterations with a frequent gain of chromosome arm 1q (>50%), gains of chromosome 7 (40%), gains on 17q (>40%) and losses on 6q (40%). Angiosarcomas secondary to irradiation often carry a MYC amplification (here 70%). show
Methylation class atypical fibroxanthoma / pleomorphic dermal sarcoma The methylation class "atypical fibroxanthoma / pleomorphic dermal sarcoma" is based on tumours with the histological diagnosis of atypical fibroxanthoma and pleomorphic dermal sarcoma. These tumours are almost always located in the actinically-damaged skin of the head and neck region; median age is 82 years (age range 60 to 99); striking predominance in males. Copy number alterations typically involve losses on chromosome arm 9p (>70%) and 13q (>90%). show
Methylation class chondroblastoma The methylation class "chondroblastoma" is based on tumours with the histological diagnosis of chondroblastoma. Cases of this class most commonly arise in tubular bones of the limbs; median age is 17 years (age range 14 to 41). Recurrent chromosomal alterations are not observed and most cases show a flat profile in copy number analysis. show
Methylation class chondrosarcoma (IDH group A) The methylation class "chondrosarcoma (IDH mutant group A)" is based on tumours with the histological diagnosis of conventional chondrosarcoma. Location is most frequently the skull base; median age is 45 years (age range 17 to 73). Cases of this methylation class carry a mutation in either IDH1 or IDH2. Recurrent chromosomal alterations are not observed and most cases show a flat profile in copy number analysis. show
Methylation class chondrosarcoma (IDH group B) The methylation class "chondrosarcoma (IDH mutant group B)" is based on tumours with the histological diagnosis of conventional chondrosarcoma. Location is predominantly the limbs; median age is 51 years (age range 16 to 79). Cases of this methylation class mostly carry a mutation in either IDH1 or IDH2. Recurrent chromosomal alterations are not observed and most cases show a flat profile in copy number analysis. show
Methylation class chondrosarcoma (clear cell) The methylation class "chondrosarcoma (clear cell)" is based on tumours with the histological diagnosis of clear cell chondrosarcoma. Location is most commonly a tubular bone of the limbs; median age is 40 years (age range 22 to 49); predominance in males. Copy number analysis frequently shows a gain of chromosome 5 (>50%). show
Methylation class chondrosarcoma (group A) The methylation class "chondrosarcoma (group A)" is based on tumours with the histological diagnosis of conventional chondrosarcoma. Location can possibly be any bone; median age is 63 years (age range 42 to 82). Cases of this methylation class are IDH1/2 wild type. Copy number alterations are predominantly whole-chromosome losses and typically involve chromosome 1 (>80%), 6 (>80%), 10 (>80%), 13 (>80%) and 14 (>90%). show
Methylation class chondrosarcoma (group B) The methylation class "chondrosarcoma (group B)" is based on tumours with the histological diagnosis of conventional chondrosarcoma. Location can possibly be any bone; median age is 59 years (age range 30 to 82). Most cases of this methylation class are IDH1/2 wild type (~80%). The copy number analysis shows numerous alterations with a frequent gain of chromosome 19 (>50%) and losses on chromosome 9p, 10p and 13q (>40% each). A homozygeous deletion of the CDKN2A locus on 9p is frequently observed (>50%). show
Methylation class chondrosarcoma (mesenchymal) The methylation class "chondrosarcoma (mesenchymal)" is based on tumours with the histological diagnosis of mesenchymal chondrosarcoma. Location can be skeletal and extraskeletal; median age is 19 years (age range 15 to 51). Cases of this class frequently carry a HEY1-NCOA2 gene fusion. The copy number analysis shows sparse alterations with a recurrent gain of chromosome arm 12q (>30%) and loss of chromosome 8p (>30%). show
Methylation class chordoma The methylation class "chordoma" is based on tumours with the histological diagnosis of chordoma. Location is the axial region mostly affecting the skull base; median age is 58 years (age range 14 to 79). The copy number analysis shows numerous alterations with a frequent gain of chromosome arm 1q (60%) and chromosome 7. Losses frequently involve chromosome arm 1p (60%), chromosome 3, 13 and 14 (>70% each). All cases express Brachyury. show
Methylation class chordoma (dedifferentiated) The methylation class "chordoma (dedifferentiated)" is based on tumours with the histological diagnosis of poorly differentiated chordoma. Location is mostly the skull base; median age is 7 years (age range 1 to 17). Copy number analysis shows a recurrent deletion of the SMARCB1 locus on chromosome arm 22q (>50%). Otherwise, the copy number profile is flat. All cases of this methylation class lack INI-1 expression. show
Methylation class clear cell sarcoma of soft parts The methylation class "clear cell sarcoma of soft parts" is based on tumours with the histological diagnosis of clear cell sarcoma of the soft tissue. Location is often the soft tissue of the limbs. Median age is 56 years (age range 18 to 78). A rearrangement of EWSR1 with ATF1 is characteristic for this methylation class. The copy number analysis shows sparse alterations with a recurrent gain on chromosome 8 (>50%). show
Methylation class clear cell sarcoma of the kidney The methylation class "clear cell sarcoma (kidney)" is based on tumours with the histological diagnosis of clear cell sarcoma of the kidney. The BCOR internal tandem duplication is characteristic for this methylation class. The copy number analysis shows sparse to numerous alterations with losses on chromosome 3, 4, 6 and 8 (>40% each). show
Methylation class control (blood) The methylation class "control (blood)" is comprised of normal tissue samples from peripheral blood. In case tumour samples display this molecular pattern, it is typically an indication of low tumour cell content in the analysed material and indicates that the extracted DNA is likely not suitable for classification by methylation profiling. show
Methylation class control (muscle tissue) The methylation class " control (muscle tissue)" is comprised of normal tissue samples from skeletal muscle. In case tumour samples display this molecular pattern, it is typically an indication of low tumour cell content in the analysed material and indicates that the extracted DNA is likely not suitable for classification by methylation profiling. show
Methylation class control (reactive tissue) The methylation class "control (reactive tissue)" is comprised of granulation tissue samples originated from vertebral disc prolapses. In case tumour samples display this molecular pattern, it is typically an indication of low tumour cell content in the analysed material and indicates that the extracted DNA is likely not suitable for classification by methylation profiling. show
Methylation class dermatofibrosarcoma protuberans The methylation class "dermatofibrosarcoma protuberans" is based on tumours with the histological diagnosis of dermatofibrosarcoma protuberans. Location is the skin and subcutaneous soft tissue of the limbs; median age is 33 years (age range 2 to 72). The COL1A1-PDGFB fusion gene based on a supernumerary ring chromosome comprising sequences of chromosomes 17q and 22q is characteristic for cases of this class. Accordingly, gains on chromosome arms 17q and 22q are frequently observed in copy number analysis. show
Methylation class desmoid-type fibromatosis The methylation class "desmoid-type fibromatosis" is based on tumours with the histological diagnosis of desmoid-type fibromatosis. Location is frequently the trunk; median age is 50 years (age range 30 to 71). Cases of this class often present with an abnormal nuclear accumulation of -catenin. Recurrent chromosomal alterations are not observed and most cases show a flat profile in copy number analysis. show
Methylation class desmoplastic small round cell tumour The methylation class "desmoplastic small round cell tumour" is based on tumours with the histological diagnosis of desmoplastic small round cell tumour. Location is mostly the trunk; median age is 17 years (age range 6 to 46); striking predominance in males. Cases of this class consistently carry an EWSR1-WT1 gene fusion. A gain of chromosome arm 1q, 3, 5 and/or 21q can be observed in up to 50% of cases. show
Methylation class endometrial stromal sarcoma (high grade) The methylation class "endometrial stromal sarcoma high-grade)" is based on tumours with the histological diagnosis of high-grade endometrial stromal sarcoma. Location is the uterus, if not associated with an extrauterine endometriosis; median age is 50 years (age range 26 to 89). Cases of this class frequently carry rearrangements involving YWHAE, FAM22 or BCOR. Copy number analysis shows recurrent choromosomal losses on chromosome arm 9p (60%) and 11q (50%). show
Methylation class endometrial stromal sarcoma (low grade) The methylation class "endometrial stromal sarcoma (low-grade)" is based on tumours with the histological diagnosis of low-grade endometrial stromal sarcoma. Location is the uterus, if not associated with an extrauterine endometriosis; median age is 48 years (age range 39 to 71). Cases of this class frequently carry rearrangements involving JAZF1, SUZ12 or PHF1. Copy number analysis shows recurrent choromosomal losses on chromosome arm 7p (50%). show
Methylation class epithelioid haemangioendothelioma The methylation class "epithelioid hemangioendothelioma" is based on tumours with the histological diagnosis of epithelioid hemangioendothelioma. Location is soft tissue and visceral, but epithelioid hemangioendothelioma may also arise in the skeleton; median age is 55 years (age range 10 to 85). Cases of this class characteristically carry a WWTR1-CAMTA1 gene fusion or less frequently a YAP1-TFE3 gene fusion. Many cases show a flat profile in copy number analysis. show
Methylation class epithelioid sarcoma The methylation class "epithelioid sarcoma" is based on tumours with the histological diagnosis of epithelioid sarcoma, either classic or proximal-type. Location is frequently the extremity; median age is 37 years (age range 12 to 68). Copy number analysis shows lossses on chromosome 22 (> 70%) and 8p (40%). All but one case of this methylation class, which carries a SMARCA4 mutation, lack nuclear INI-1 expression. show
Methylation class extraskeletal myxoid chondrosarcoma The methylation class "extraskeletal myxoid chondrosarcoma" is based on tumours with the histological diagnosis of extraskeletal myxoid chondrosarcoma. Cases of this class most commonly arise in the soft tissue of the limbs; median age is 55 years (age range 39 to 79). A rearrangement of NR4A3, frequently with EWSR1, is characteristic for this methylation class. Recurrent chromosomal alterations are not observed and most cases show a flat profile in copy number analysis. show
Methylation class fibrous dysplasia The methylation class "fibrous dysplasia" is based on tumours with the histological diagnosis of fibrous dysplasia, either in its monostotic or polyostotic form. Location is the skeleton, frequently a bone of the extremities; median age is 34 years (age range 15 to 61). Cases of this class consistenly carry a GNAS hotspot mutation at codon 201. Recurrent chromosomal alterations are not observed and most cases show a flat profile in copy number analysis. show
Methylation class gastrointestinal stromal tumour The methylation class "gastrointestinal stromal tumour" is based on tumours with the histological diagnosis of gastrointestinal stromal tumour. Location is mostly the gastrointestinal tract; median age is 65 years (age range 30 to 94). Cases of this class frequently carry a KIT or PDGFRA mutation. Copy number analysis show frequent losses on chromosome 14 (>70%), 1p (40%) and 22q (>50%). show
Methylation class giant cell tumour of bone The methylation class "giant cell tumour of bone" is based on tumours with the histological diagnosis of giant cell tumour of bone. Cases mostly arise in the epiphyseal-metaphyseal region of long tubular bones; median age is 29 years (age range 22 to 75). Cases of this class consistenly carry a H3F3A G34W/L hotspot mutation. Recurrent chromosomal alterations are not observed and most cases show a flat profile in copy number analysis. show
Methylation class infantile fibrosarcoma The methylation class "infantile fibrosarcoma" is based on tumours with the histological diagnosis of infantile fibrosarcoma. Location is the superficial and deep soft tissue of the extremities, trunk and head/neck; median age is <1 years (age range 0 to 1). The ETV6-NTRK3 fusion gene is characteristic for cases of this methylation class. Copy number analysis shows recurrent gains on chromosome 11 (>60%), 15 and 20 (each 40%). show
Methylation class inflammatory myofibroblastic tumour The methylation class "inflammatory myofibroblastic tumour" is based on tumours with the histological diagnosis of inflammatory myofibroblastic tumour. These tumours are located in the soft tissue and viscera; median age is 10 years (age range 2 to 17). ALK rearrangements are frequently found in cases of this class. Most cases show a flat profile in copy number analysis. show
Methylation class leiomyoma The methylation class "leiomyoma" is based on tumours with the histological diagnosis of uterine leiomyoma. Median age is 38 years (age range 31 to 52). Recurrent chromosomal alterations are not observed and most cases show a flat profile in copy number analysis. show
Methylation class leiomyosarcoma The methylation class "leiomoysarcoma" is based almost completely on tumours with the histological diagnosis of extrauterine leiomoysarcoma. Cases of this methylation class are predominantly located extrauterine (retroperitoneum); median age is 57 years (age range 39 to 87). Copy number alterations are numerous with a frequent losses of chromosomes 13 (>80%), 10 (>70%) and 16q (>60%). Gains frequently involve chromosome arm 5p, 8q and 17p (40% each). show
Methylation class lipoma The methylation class "lipoma" is based on tumours with the histological diagnosis of lipoma. These tumours are mostly located in the superficial soft tissue; median age is 54 years (age range 29 to 79). Recurrent chromosomal alterations are not observed and most cases show a flat profile in copy number analysis. Caution: MDM2 amplifications are not compatible with lipoma. show
Methylation class low-grade fibromyxoid sarcoma The methylation class "low-grade fibromyxoid sarcoma" is based on tumours with the histological diagnosis of low-grade fibromyxoid sarcoma. These tumours are most common in proximal extremities and the trunk; median age is 34 years (age range 18 to 56). Cases of this class consistently carry a FUS-CREB3L2/1 gene fusion. Most cases show a flat profile in copy number analysis. show
Methylation class malignant peripheral nerve sheath tumour The methylation class "malignant peripheral nerve sheath tumour" is based on tumours with the histological diagnosis of malignant peripheral nerve sheath tumour, either sporadic or associated with Von Recklinghausen's Disease (neurofibromatosis type 1). Cases of this class are mostly located in the retroperitoneum and the extremities; median age is 22 years (age range 9 to 54). Copy number alterations are numerous with frequent gains involving chromosome arm 7p (60%), 8q (70%), segmental gains of 17q (60%), and losses on chromosome arm 1p (60%), 9p (>60%), 10q (>60%), 11q (>70%) and a distinct segmental deletion of 17q11.2 (>60%) covering the NF1 locus. All cases of this class have a loss of histone H3K27 trimethylation. show
Methylation class malignant rhabdoid tumour The methylation class "malignant rhabdoid tumour" is based on tumours with the histological diagnosis of malignant rhabdoid tumour. Cases of this class comprise tumours located in the renal and extrarenal region (without the CNS); median age is 1 year (age range 0 to 11). Copy number analysis shows a frequent segmental deletion on chromosome arm 22q11.2 involving the SMARCB1 locus (>80%). Almost all cases of this methylation class present with loss of nuclear INI-1 expression. show
Methylation class melanoma (cutaneous) The methylation class "melanoma" is based on tumours with the histological diagnosis of melanoma. Cases of this class comprise malanoma metastases originated from the skin; median age is 60 years (age range 26 to 87). The copy number analysis shows numerous alterations with frequent gains on chromosome 1q (>50%), 6p (>50%), 7p (>70%) and losses on chromosome 6q (60%), 9p (>60%) and 11q (>70%). show
Methylation class myositis ossificans The methylation class "myositis ossificans" is based on tumours with the histological diagnosis myositis ossificans. They arise often in locations susceptible to trauma such as extremities, shoulder, buttock; median age is 13 years (range 9 to 17). Recurrent chromosomal alterations are not observed and many cases show a flat profile in copy number analysis. show
Methylation class myositis proliferans The methylation class "myositis proliferans" is based on tumours with the histological diagnosis myositis proliferans. By definition, they arise in intramuscular location. The subcutaneous counterpart has the same cellular composition and is termed proliferative fasciitis. The median age is 64 years (range 28 to 79). Recurrent chromosomal alterations are not observed and most cases show a flat profile in copy number analysis. show
Methylation class myxoid liposarcoma The methylation class "myxoid liposarcoma" is based on tumours with the histological diagnosis myxoid liposarcoma. Location is typically the deep soft tissue of extremities, mainly within the muscles of the thigh. The median age is 52 years (range 32 to 84). Molecularly, these cases are characterized by a FUS-DDIT3 fusion gene (>95%) or by a EWSR1-DDIT3 fusion gene (<5%). Myxoid liposarcomas frequently carry a TERT promoter mutation (>70%). Most cases show a flat profile in copy number analysis. show
Methylation class neurofibroma The methylation class "neurofibroma" is based on tumours with the histological diagnosis of neurofibroma, either sporadic or associated with Von Recklinghausen's Disease (neurofibromatosis type 1). Cases of this class are most commonly located dermal; median age is 32 years (age range 17 to 43). The copy number profile is flat except for a distinct segmental deletion of 17q11.2 covering the NF1 locus in >40% of cases. show
Methylation class neurofibroma (plexiform) The methylation class "plexiform neurofibroma" is based on tumours with the histological diagnosis of plexiform neurofibroma of the plexiform variant, either sporadic or associated with Von Recklinghausen's Disease (neurofibromatosis type 1). Plexiform neurofibromas have a slightly increased risk for malignant transformation. Cases of this class are most commonly located in the skin; median age is 13 years (age range 5 to 39). The copy number profile is flat except for a distinct segmental deletion of 17q11.2 covering the NF1 locus in up to 30% of cases. show
Methylation class nodular fasciitis The methylation class "nodular fasciitis" is based on tumours with the histological diagnosis of nodular fasciitis. Cases of this class are most commonly located in the subcutaneous soft tissue; median age is 14 years (age range 4 to 19). Cases of this class frequently carry a MYH9-USP6 gene fusion. Recurrent chromosomal alterations are not observed. Most cases show a flat profile in copy number analysis. show
Methylation class ossifying fibromyxoid tumour The methylation class "ossifying fibromyxoid tumour" is based on tumours with the histological diagnosis of ossifying fibromyxoid tumour. Cases of this class are most commonly located in the soft tissue of extremitites and the trunk; median age is 50 years (age range 41 to 77). Cases of this class frequently carry rearrangements of chromosome arm 6p21 involving PHF1. Copy number analysis shows frequent losses on chromosome 6q. show
Methylation class osteoblastoma The methylation class "osteoblastoma" is based on tumours with the histological diagnosis of osteoblastoma. Cases of this class are most commonly located in tubular bones, the spine and the craniofascial bones (mandible); median age is 15 years (age range 8 to 28). FOS alterations were described for this entity. Recurrent chromosomal alterations are not observed and most cases show a flat profile in copy number analysis. show
Methylation class osteosarcoma (high grade) The methylation class "osteosarcoma (high-grade)" is based on tumours with the histological diagnosis of conventional (high-grade) osteosarcoma. These tumours are mostly located in the tubular bones of the extremities; median age is 15 years (age range 5 to 78). Copy number alterations are numerous with frequent gains on chromosome 6p (70%), 8q (60%), and losses on chromosome 6q (70%), 10 (80%) and 13 (80%). show
Methylation class rhabdomyosarcoma (MYOD1) The methylation class "rhabdomyosarcoma (MYOD1)" is based on tumours with the histological diagnosis of rhabdomyosarcoma that exhibit spindle cell or sclerosing features in most cases. Location is frequently the head and neck region; median age is 17 years (age range 4 to 59). Cases of this class carry a hotspot mutation in MYOD1. Copy number analysis shows frequent whole-chromosome losses, mostly involving chromosome 13q (80%) and losses on chromosome 10p (> 60%). The name given here is provisional. show
Methylation class rhabdomyosarcoma (alveolar) The methylation class "rhabdomyosarcoma (alveolar)" is based on tumours with the histological diagnosis of alveolar rhabdomyosarcoma. Primary location is frequently the deep soft tissue of extremities, this class is predominantly composed of metastasic cases; median age is 13 years (age range 2 to 26). Cases of this class carry a translocation between FOXO1 and PAX3 or PAX7. The copy number analysis shows numerous copy number alterations including amplification of the CDK4 or MYCN locus (~20% each). show
Methylation class rhabdomyosarcoma (embryonal) The methylation class "rhabdomyosarcoma (embryonal)" is based on tumours with the histological diagnosis of embryonal rhabdomyosarcoma, including the botryoid variant. Location is frequently the head and neck region or the genitourinary system; median age is 11 years (age range 1 to 30). Copy number analysis shows frequent whole-chromosome gains, mostly involving chromosome 8 (80%), and losses on chromosome 9p involving the CDKN2A/B locus (> 40%). show
Methylation class sarcoma (MPNST-like) The methylation class "sarcoma (MPNST-like)" is based on tumours with typical morphological features of malignant peripheral nerve sheath tumour, but retained expression of the H3K27 trimethylation marker. These tumours often are located (para-)spinal; median age is 50 years (age range 10 to 77). Copy number alterations are numerous with frequent losses on chromosome arm 3q (>80%), 5q (>80%), 9p (100%) and 17q (>70%). Copy number analysis shows a high frequency of CDKN2A/B homozygeous deletions on chromosome arm 9p (> 40%). Further molecular features of this class include mutations in NF1. The name given here is provisional. show
Methylation class sarcoma (RMS-like) The methylation class "sarcoma (RMS-like)" is based on tumours with the histological diagnosis of malignant CNS sarcoma / tumour not otherwise specified. Median age is 7 years (age range 0 to 76). The molecular hallmark of this class are DICER1 mutations (>90%), either somatic or inherited, often together with MAPK pathway alterations (>70%). Copy number profiles range from relatively flat to complex. Rhabdomyosarcoma of the genitourinary tract with DICER1 mutations may also assign to this methylation class. The name given here is provisional. show
Methylation class schwannoma The methylation class "schwannoma" is based on tumours with the histological diagnosis of schwannoma. Location is frequently a peripheral nerve of the upper extremity followed by cranial nerve VIII; median age is 26 years (age range 12 to 64). The copy number profile is flat except for a deletion of chromosome arm 22q covering the NF2 locus in up to 40% of cases. show
Methylation class sclerosing epithelioid fibrosarcoma The methylation class "sclerosing epithelioid fibrosarcoma" is based on tumours with the histological diagnosis of sclerosing epithelioid fibrosarcoma. These tumours typically express MUC4 and may carry FUS-CREB3L2 gene fusions. Location is frequently the soft tissue of the limbs. They primarily arise in adults. Copy number analysis shows numerous copy number alterations with frequent losses on chromosome 22q (>80%). show
Methylation class small blue round cell tumour with BCOR alteration The methylation class "small blue round cell tumour with BCOR alteration" is based on tumours with the histological diagnosis of undifferentiated small blue round cell tumour, not otherwise specified, Ewing sarcoma and Ewing-like sarcoma. Tumours of this methylation class most commonly carry BCOR-CCNB3 gene fusions, arise in soft tissue or bone of children, adolecents or young adults (age range 0 to 20 years). Tumours in infants (<1 year) matching with this class typically carry BCOR internal tandem duplications or point mutations. Copy number alterations are sparse and most cases of this class show a flat profile in copy number analysis. show
Methylation class small blue round cell tumour with CIC alteration The methylation class "small blue round cell tumour with CIC alteration" is based on tumours with the histological diagnosis of Ewing sarcoma, Ewing-like sarcoma and undifferentiated small blue round cell sarcoma, not otherwise specified. Location is almost always the soft tissue; median age is 37 years (age range 16 to 49). Cases of this class frequently carry CIC-DUX2/4 gene fusions. Copy number alterations are overall sparse, and if, then mostly involve gains on chromosome 6 and 8 (>30% each). show
Methylation class solitary fibrous tumour The methylation class "solitary fibrous tumour" is based on tumours with the histological diagnosis of solitary fibrous tumour. Location is the intracranial and peripheral soft tissue; median age is 57 years (age range 15 to 83). Cases of this class consistently carry a NAB2-STAT6 gene fusion. Cases of this class consistently show a strong nuclear relocation in the STAT6 staining. Recurrent chromosomal alterations are not observed and most cases show a flat profile in copy number analysis. show
Methylation class squamous cell carcinoma (cutaneous) The methylation class "squamous cell carcinoma (cutaneous)" is based on tumours with the histological diagnosis of cutaneous squamous cell carcinoma. Location is mostly the actinically-damaged skin of the head and neck region; median age is 73 years (age range 55 to 90). Molecularly, cases of this class frequently carry TERT promoter mutations. Copy number alterations are numerous with frequent losses on chromosome arm 9p (>80%). show
Methylation class synovial sarcoma The methylation class "synovial sarcoma" is based on tumours with the histological diagnosis of synovial sarcoma. Location is mostly the soft tissue of extremities; median age is 34 years (age range 12 to 70). Cases of this class consistently carry a SS18-SSX gene fusion. Most cases show a flat profile in copy number analysis. show
Methylation class undifferentiated sarcoma The methylation class "undifferentiated sarcoma" is based on tumours with the histological diagnosis of undifferentiated (pleomorphic) sarcoma, myxofibrosarcoma and pleomorphic liposarcoma. Location is the soft tissue mostly of the extremitites; median age is 72 years (age range 21 to 85). The copy number analysis shows numerous alterations with frequent losses on chromosome 1q, 2q, 9p and 13q (>60%), and gains on chromosome 1p, 5p and 7p (40%). show
Methylation class well- / dedifferentiated liposarcoma The methylation class "well- / dedifferentiated liposarcoma" is based on tumours with the histological diagnosis of well-differentiated and dedifferentiated liposarcoma. Location is most commonly the deep soft tissue of the trunk (retroperitoneum > 60%); median age is 59 years (age range 41 to 80). Cases of this methylation class typically carry an amplification on chromosome arm 12q13-15 involving the MDM2 locus. Otherwise, the copy number profile mostly shows additional chromosomal alterations. show