Undifferentiated pleomorphic sarcoma

From Compendium of Cancer Genome Aberrations
Jump to navigation Jump to search

Soft Tissue and Bone Tumours (Who Classification, 5th ed.)

Primary Author(s)*

Maxine J Sutcliffe, PhD, FACMG, CCMG

WHO Classification of Disease

Structure Disease
Book Soft Tissue and Bone Tumours (5th ed.)
Category Bone tumours
Family Other mesenchymal tumours of bone
Type Undifferentiated pleomorphic sarcoma
Subtype(s) N/A

Related Terminology

Acceptable N/A
Not Recommended Malignant fibrous histiocytoma of bone; pleomorphic fibrosarcoma of bone

The WHO 5th Edition 2020 classifies Undifferentiated pleomorphic sarcoma (UPS) as a neoplasm of bone UPS-B.

Undifferentiated Pleomorphic Sarcoma (UPS) evidences in soft tissue and bone. [1]

  • Soft Tissue (UPS-S): UPS, one of the most common soft-tissue sarcomas in adults, representing 10–20% of all soft tissue sarcomas (STSs).
  • Bone (UPS-B): UPS of bone is rare, accounting for only about 2% of all primary bone neoplasms.

The majority of references quoted relate to UPS-S.

Gene Rearrangements

Undifferentiated Pleomorphic Sarcoma (UPS) lacks specific definable gene rearrangements rendering it a diagnosis of exclusion.[2] [3] UPS is typified by highly complex karyotype, extreme aneuploidy, polysomy, polyploidy, and excessive genomic instability, but without any identifiable, defining characterizing diagnostic aberrations.

  • The term cancer “driver” genes in UPS refers to recurrent alterations in genes such as ATRX, RB1 and TP53 tumor suppressors. From a molecular standpoint, unlike other soft tissue sarcomas, UPS does not manifest any known translocations or driver/donor fusions. [2][3]
  • In this context, the term “cancer driver genes” (in addition to the cited tumor suppressors genes) documented in UPS include: H3F3A, ZFHX3, CSMD3, PRPRT, TRIO, CLTC, PDGFRB, ALK, PTVH1, RET, ERBB4, JAK3, GATA1, PIK3CG, RARA, MYH9.[4]
Driver Gene Fusion(s) and Common Partner Genes Molecular Pathogenesis Typical Chromosomal Alteration(s) Prevalence -Common >20%, Recurrent 5-20% or Rare <5% (Disease) Diagnostic, Prognostic, and Therapeutic Significance - D, P, T Established Clinical Significance Per Guidelines - Yes or No (Source) Clinical Relevance Details/Other Notes
TRIO TERT Trio Rho Guanine Nucleotide Exchange Factor fusion involving the 5’ region of TRIO (5p15.2) exon 33,34 or 40 forming an in-frame chimeric transcript with 3’ Telomerase Reverse Transcription TERT exons. [5] [4]
  • Non-translational fusion TRIO::TERT leading to massive over-expression of TERT. [5]
  • TRIO is a target of 5p amplification in UPS.

Not specific to UPS

Rare ~ 4% of UPS N/A No
  • TRIO::TERT fusion is a rare gene rearrangement in a small subset of non-translational soft tissue sarcomas including UPS.
  • Less frequent TRIO partners include LINC01504 (9q21.3) or ZNF558 (19p13.3).
  • The fusion is considered a secondary oncogenic event (rather than primary), hence non-diagnostic. [5] [6]
TMTC2 NTRK3
  • Intronic fusion involving Exons 1-9 of the N-terminal Transmembrane and Tetratricopeptide Repeat Containing 2 (TMTC2) gene acting as the 5’ driver partner with the 3’ Exons 15-36 kinase domain of the Neurotrophic Receptor Tyrosine Kinase 3 (NTRK3). [7]
  • NTRK family fusions typically lead to constitutive activation of the TRK signaling pathway that contributes to tumor proliferation and progression. [4].
 TMTC2 12q21.31 fused with NTRK3 15q25.3-q26.2

Methodology for fusion identification by NGS, confirmed by IHC and interphase FISH. [7]

Single case in UPS N/A No Reported in a single case.  Implications of this fusion are it's potential responsiveness to TRK family of targeted therapies. [7]
LMNA NTRK1
  • Fusion involving Exons 1-2 of the N-terminal Lamin A/C (LMNA)  gene acting as the 5’ driver promoter  with the 3’ Exons 11-17 kinase domain of the Neurotrophic Receptor Tyrosine Kinase 1 (NTRK1). [8]
  • NTRK family fusions result in constitutive activation of the TRK signaling pathway that contributes to tumor proliferation and progression. [4]
 LMNNA 1q21.2-q21.3 fused with NTRK1 1q23.1.

Methodology for fusion identification by NGS. [8]

Single case in UPS N/A No Disease progression in this case was not halted with typical management (resection, radiation and chemotherapy).  Identification of this LMNA::NTRK1 fusion and the aggressive clinical presentation led to the patient receiving treatment with 450mg/day crizotinib orally. Patient maintained near-complete clinical response (follow-up 18 months). [8]

Individual Region Genomic Gain/Loss/LOH

Multiple numerical/structural chromosome aberrations are highly recurrent, but not definitive for UPS due to their extensive range, lack of specific pattern and seemingly random occurrence [1] [9].  Also some reports combine soft tissue UPS with myxofibrosarcoma, others describe UPS of bone/soft tissue due to their same classification and relative indistinguishable morphology. [1] [9]. Nonetheless, conventional chromosome analysis, CGH microarray, and FISH demonstrate frequent reoccurring CN change (bolded cited in multiple studies). [4] [10]

Gain:

  • Both p and q arms, chromosomes 1,2,7,11,19, X
  • p arms chromosomes 3,4,5,6,12,16,17
  • q arms chromosomes 4,6,8,9,12,14,15,17,20,22

Loss:

  • Both p and q arms, chromosomes 8,9,10
  • p arms chromosomes  8,9
  • q arms 1,2,4,5,7,13,16,18)
Chr # Gain, Loss, Amp, LOH Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size] Relevant Gene(s) Diagnostic, Prognostic, and Therapeutic Significance - D, P, T Established Clinical Significance Per Guidelines - Yes or No (Source) Clinical Relevance Details/Other Notes
None currently diagnostic All aberrant mechanisms, occurring sequentially, or simultaneously, are demonstrated but none are diagnostically exclusive for UPS N/A N/A N/A N/A
  • UPS lacks specific identifiable diagnosable chromosomal/molecular features or mechanisms rendering this classification having a “default” diagnosis subsequent to exclusion of other highly similar sarcomas.
  • Other soft tissue sarcomas within the differential diagnosis for exclusion  include: dedifferentiated liposarcoma (DDLPS), leiomyosarcoma (LMS), myxofibrosarcoma (MFS), pleomorphic liposarcoma (PLS), malignant peripheral nerve sheath tumor (MPNST), angiosarcoma (AS) and extra-skeletal osteosarcoma (ESOS). [3] [11] [12]
  • Classifying/re-classifying soft tissue sarcomas is clearly important (eg. MDM2 in DDLS). [11] [12]
  • Concurrently, in view of the incidence and high risk/poor prognostic outcome, multiple research studies to identify key features of UPS as well as specific biomarkers, prognostic indicators and targets or pathways for potential therapeutic strategies are sought to optimize patient management. [2] [3] [4] [5] [13]

Characteristic Chromosomal or Other Global Mutational Patterns

  • UPS is “characterized” by a high degree of genomic instability which is a hallmark of its complex, chaotic and non-specific molecular profile but high-grade, high-risk morphology. [2] [3] Highly heterogeneous, complex karyotypes showing extensive copy number gain/loss including trisomy, pentasomy, hexasomy, and sex chromosome polysomy; bizarre structural changes such as dicentric, ring formation and unidentifiable “markers”. Evidence of massive instability results from amplification, chromothripsis, and LOH (loss of heterozygosity). [12] [13]
  • A distinctive phenotype seen in undifferentiated soft tissue sarcomas is genome-wide LOH reported from a pan-cancer analysis of >10,000 cancers (TCGA - (The Cancer Genome Atlas). [6] Whole genome doubling (WGD) is a key macroevolutionary event that linked to chromothripsis.  WGD is rare in many tumor types but undifferentiated soft tissue sarcomas show >90% WGD. [6] [14] [15]  Coupling a near-haploid precursor with WGD is reported to have a pan-cancer prevalence of ~0.2%, but was observed in 3% of TCGA analyses and confirmed as enriched in UPS. [6] [14].
Chromosomal Pattern Molecular Pathogenesis Prevalence -

Common >20%, Recurrent 5-20% or Rare <5% (Disease)

Diagnostic, Prognostic, and Therapeutic Significance - D, P, T Established Clinical Significance Per Guidelines - Yes or No (Source) Clinical Relevance Details/Other Notes
Numerical Gain/Loss

Polysomy

Copy Number (CN) Gain/Loss primarily trisomy but also pentasomy, hexasomy etc: 2,11,12,14,18,21,22,Y. [4] [5]

Sex chromosome polysomy.

Common P. Features such as giant nuclei recognized as adverse prognostic indicators. [15] No
  • Marked chromosome aneuploidy cell-to-cell variability.
  • Range from near-haploid to hypo-octoploid with modal chromosome 22-180 count. [6] [12]
AMPD2 CN Gain CN gain at 1p13.3 Adenosine Monophosphate Deaminase 2 (AMPD2) locus leads to high level expression. [16] Unknown P. Robust prognostic biomarker for worse outcome in UPS. [16] No
  • Survival association-testing of AMPD2 gene expression and survival data significantly highly correlated with poor outcome. [16]
  • Knockdown of AMPD2 in vitro confirmed inhibited proliferation and in vivo tumorigenesis. [16]
Polyploidy. PGCC Chromothripsis and Whole Genome Doubling (WGD) presents as histopathologically identifiable giant nuclei.  Single cell DNA sequencing revealed polyploid giant cancer cells (PGCC). [5] [6] [14] [15] Rare-Recurrent P. Evidence of instability associated with high risk and adverse prognosis No
  • Whole genome doubling (WGD), a key macroevolutionary event, associated with instability resulting from chromothripsis and LOH. [14]
  • WGD shows variable percentage in some cancers but reported prevalence 90% in undifferentiated sarcomas.
  • 5-10 copies of each chromosome in >4% of nuclei correlated with giant nuclei reported in histopathology in a percentage of cells in UPS. [5] [15]
  • Chromothripsis-like events leading to polyploid giant cancer cells (PGCCs), confirm the role of chomothripsis as a key-driver phenomenon. [15]
  • Clonal and subclonal multinucleation was demonstrated with twice WGD of 6.2n against a tumor background of 3.3n. [15]
Structural aberrations, resulting in highly complex karyotypes.

Preferential chromosomal deletions of tumor suppressor genes.

  • Chromosome segmental loss, deletions and chromothripsis lead to formation of rings, dicentric chromosomes, telomere associations and unidentifiable markers.
  • Intra-chromosomal deletions preferentially involve loss of key tumor suppressor genes: 17p13.1 (TP53) (50%), 13q14.2 (RB1)(68%), 9p21 (CDKN2A), 10q23.31 (PTEN), 11q22.3 (ATM), Xq21.1 (ATRX). [2] [4] [17]
 Common P. Evidence of instability associated with high risk and adverse prognosis. No Multiple mechanism, associated with tumor suppressor gene loss including homozygous and heterozygous deletion/alteration, mainly but not exclusively loss-of-function. [17] [18]
Amplification
  • Genome wide amplification, double minutes (dmin), homogeneously staining regions (hsr) with frequently involving 1q,5p,6q and 12q, 20q. [6]
  • Recurrent amplification of regions overlapping oncogenes, significance unknown. 1p36,3q26,4q,7q,8q. [4] [6] [18]
  • Subset (~10%) amplification of 11q22 (YAP1) and 3p11 (VGLL3). [6]
  • Amplification of locational subsets including 4q12 (PDGFRA), 5q32 (PDGFRB), 7p11.2 (EGFR), 4q12 (KIT), 4q11-q12 (KDR aka VEGFR2). [2]
  • Amplification of Interleukin-7 receptor protein (IL7R). IL7R often occurring alongside mutated KMT2C. [2] [19]
 Recurrent P. Evidence of instability associated with high risk and adverse prognosis

Significance-potentially targetable. [2] [19]

No
  • Amplification, key mechanism of instability, often involves over-expression of oncogenes that drive cell cycle and tumor progression. [6] [18]
  • Amplification 12q13-q15 (MDM2,CDK4) frequently associated with liposarcoma. UPS demonstrating MDM2-amp, although histologically indistinguishable from dedifferentiated liposarcoma (DDLPS), is resulting in reclassification. [11]
  • Amplification of 11q22 (YAP1)/3p11 (VGLL3), identified in 10% of UPS.  Activating genes involved in cellular survival and proliferation. [6]
  • IL7R associated with gain of function/over-expression alterations noted in many cancer types.  In UPS, IL7RA amplification was described in 19% along with KMT2C alterations in 16%. [2] [19]
LOH Loss of Heterozygosity (LOH), often coupled with whole genome doubling (WGD), significant UPS.  Not withstanding LOH contributing to massive genomic instability, it is not entirely random in UPS. However, pan-cancer solid tumor studies, highlight high frequency of LOH, not specific to soft tissue sarcomas.   Genome-wide P. Evidence of instability associated with high risk and adverse prognosis No Although UPS is characterized by high genomic instability, recurrent regions are described. In particular “double hits” that occur as a result of alteration/LOH noted in key tumor suppressor gene regions such as 13q14-q21 (RB1), 17p13.1 (TP53), 9p21.1-21.1 (CDKN2A), and 10q21.1-q23.2 (PTEN). [12] [14]
Chromothripsis
  • Chromothripsis, describes a phenomenon of catastrophic shattering leading to thousands of clustered rearrangements of one or more chromosomes or chromosomal regions and is a hall mark of high genomic instability.
  • Chromothripsis is especially prevalent in UPS and similar sarcomas with some studies indicating a frequency >70%. [20]
  • Although occurring anywhere in the genome, chromosome “hotspots” demonstrate that chromothripsis is not entirely random. [6] [20]
  • Chromothripsis is a key driver of heterogeneity in the formation of giant nuclei and PGCC in UPS. [15]
 Genome-wide P. Evidence of instability associated with high risk and adverse prognosis No Chromothripsis “hotspots” appear to highlight a phenomenon of selective pressure for survival, a conclusion based on more frequently observed in the location of tumor suppressor and onco-genes such as:

17p13.1 (TP53), 9p21.3 (CDKN2A/CDKN2B). 13q14-q21 (RB1), 8q24.12-q24.13 (MYC), 11q13.3 (CCND1). [6] [20]

Gene Mutations (SNV/INDEL)

UPS is associated with a number of highly significant, often highly recurrent, key cancer gene aberrations that are used in adverse risk stratification and management but, of themselves, are not exclusive to UPS and therefore are not “diagnostic”.  

Gene Genetic Alteration Tumor Suppressor Gene, Oncogene, Other Prevalence -

Common >20%, Recurrent 5-20% or Rare <5% (Disease)

Diagnostic, Prognostic, and Therapeutic Significance - D, P, T   Established Clinical Significance Per Guidelines - Yes or No (Source) Clinical Relevance Details/Other Notes
TP53


  • Deletion, and/or loss of function leading to p53 pathway inactivation, tumor progression and genomic instability.
  • Additionally, TP53 can acquire oncogenic gain of function activity through missense variation. [21] [22]
 TP53 is typically a Tumor Suppressor Gene, but when mutated has oncogenic activity. [2] Common

Occurs in 12-20% of UPS. Part of broader highly heterogeneous landscape. Seen in high grade or recurrent UPS cases. [4]

P. Adverse prognosis, especially when exhibiting oncogenic activity

Potentially significant-targetable, therapeutic. [4]

No
  • TP53’s role as the “guardian of the genome” is preventing cell proliferation, promoting apoptosis and maintaining DNA integrity.
  • TP53 is highly prevalent in UPS reported in 33-50% often co-occurring with loss of RB1. [4]
  • Typically, loss of TP53 is associated with an adverse prognosis.  A mutant gain of function is also noted and highly associated with advanced malignancies and poor prognosis. 
  • Gain of function alterations are potentially significant in the development of targeted therapeutic strategies. [21] [22]
RB1


  • Deletion/loss of function alterations of RB1 often co-occur with loss of function of TP53 gene.
  • Alterations in RB1 lead to dysfunctional cell cycle control by removing cell cycle checkpoints that result in uncontrolled cell proliferation.
 Tumor Supressor Gene Common.

88% of UPS demonstrate alterations in either RB1 or TP53 and co-occurrence of both is seen in 60%. [17]

P. Adverse prognosis
  • RB1 is highly altered, one of the most frequent genes associated with CN loss in UPS.
  • Co-occurrence of loss of both RB1 and TP53 is described as a hallmark of high grade UPS. [17]
  • Skp2 is an oncogenic protein that drives cell proliferation via its p1 and p27 binding sites. P27 is a cyclin-dependent kinase that is targeted for degradation by Skp2. [17] 
  • A correlation was found between absent Rb and p53 expression and positive expression of Skp2 illustrating a co-dependency of Rb/p53 on Skp for cellular survival. It is suggested that this features could potentially be exploited for therapeutic strategies. [4] [17]                               
ATRX
  • Loss and/or loss-of-function alterations of Alpha-Thalassemia/ Mental Retardation Syndrome X-linked gene results in DNA methylation loss and increased transposable element expression.
  • ATRX loss affects it’s role as an epigenetic regulator of chromatin accessibility. (ATRX functions in histone modification and heterochromatin remodeling).
  • Additionally, ATRX deficiency negatively interferes with telomere maintenance through interaction with the ALT telomere length pathway. [23]
 Tumor Supressor Gene Common.

Variously reported occurring in 20-37% of UPS cases. [4] [24]

P. Adverse prognosis No
  • ATRX loss of function alterations are seen in ~35% of sarcomas including UPS. [24]
  • Significantly associated in UPS with worse disease-specific survival (DSS). [23] [24]
  • Aggressive tumor proliferation especially if loss in combination with deletion TP53. [23] [24]
CDKN2A Deletion, including homozygous loss resulting in uncontrolled cell cycle progression. Tumor Supressor Gene Common P. Adverse prognosis No
  • Notably high frequency deletion in common with RB1 deletion/ alterations and alterations in MYC in USP-B. [4]
  • Deletion along loss of TP53 in the absence of MDM2 amplification described in very rare cardiac UPS. [4] [25]
  • In USP-S, loss along with TP53, RB1 and dependency on Skp2. [4]
PIK3CA Missense variant within exons 9 or 20, activating the P13K/mTOR pathway.

Co-occurrence described with PTEN loss or KRAS alterations. [26]

Oncogene (but not as primary driver) Rare P. Adverse prognosis. No
  • PIK3CA alterations co-occurs with PTEN loss reported in 12-18% of soft tissue sarcomas including UPS; part of complex genetic changes. [26]
  • KRAS alterations are rarely reported in soft tissue sarcomas but noted in a small subset of UPS co-occurring with PIK3CA, NF1 alterations, or TP53 loss. [26] [27]
  • Potentially significant as a therapeutic target. [4]
KMT2C Loss of function, by truncation/missense variation that reduces or eliminates histone methylation activity Acts as a tumor suppressor since loss leads to impaired H3K4 methylation. [19] Recurrent
  • Alterations correlate with increased tumor burden.
  • Potential targetable significance
 No Noted in 16% of UPS, co-occurs with amplification of IL7R in 19% of UPS. [2] [19].
NF1 Loss of function alteration or deletion Acts as a tumor suppressor gene in UPS leading to increased RAS signaling and tumor development. [26] Recurrent Potential significance as a-biomarker for UPS.. No
  • NF1-related microRNAs used to quantify mRNA and expression levels were found to be significantly decreased in UPS. [27]
  • Occasionally, NF1 appears to co-occur with RAS oncogenes, eg KRAS variation. [27]

Epigenomic Alterations

UPS is not defined by specific epigenetic changes, however:.  

  • Epigenetic regulators and miRMA have been identified, and elevated DNA methylation patterns are noted. [12]
  • DNMT3 shows increased methylation and methylation of histones H3K4me3 and H3K9 me3 also reported to be elevated. [12]
  • Tumor-associated macrophages (TAMs) produce cytokines including TGFβ which could aberrantly activate downstream signaling.  The percentage of TAMs has been found to be a prognostic factor in UPS. In a clinical trial, the percentage of TAMs expressing PD-L1 were more likely to respond to Pembrolizumab and had a better progression-free survival [4]
  • Studies indicate UPS has an inflammatory microenvironment, high expression of antigen presentation genes and regulatory T-cell genes.[4]
  • Numerous genetic and epigenetic aberrations in UPS have been investigated and are contributing to the development of targeted therapies.[4]
  • Hyperactivation of the immune system makes UPS a potential candidate for immunotherapy with checkpoint inhibitors (ICIs). [6]  Although ICIs are not epigenomic alterations, their expression is often regulated by underlying epigenomic alterations. [4] [6]

Genes and Main Pathways Involved

UPS is associated with a number of highly significant genetic pathways.  Despite not having a definitive diagnosis, identification of these pathways is leading to potential therapeutic strategies for UPS management Put your text here and fill in the table

Gene; Genetic Alteration Pathway Pathophysiologic Outcome
YAP, LATS1/2
  • Large tumor suppressors are core kinases, functionally phosphorylating and inhibiting the effector Yes-Associated Protein. [28] [29]
  • Nonsense/frameshift alterations disrupt the LATS1/2 function.
  • YAP/TAZ with PDZ-binding motif, transcriptional coactivators. [29]
  • YAP co-regulating with FOXM1 transcription factor, are critical in  sarcomagenesis - specifically fibrosarcoma, liposarcoma and undifferentiated pleomorphic sarcoma. [28]
 Hippo pathway

A highly conserved signaling transduction kinase cascade involving MST1/2 and LATS1/2

  • Deregulated in >25% of soft tissue sarcomas via stabilization of YAP expression. [28]
  • Disruption affects organ size, cell regeneration and tissue homeostasis via control of cell proliferation and apoptosis.
YAP1, VGLL3, TEAD
  • Amplification of 11q22 (YAP1) and 3p11 Vestigial-like family member 3 (VGLL3) are opposing co-expressed factors that compete for the TEAD-binding domain transcription factors.  
  • VGLL3-TEAD promotes expression of LATS2, inactivating YAP/RAZ.
  • YAP1-TEAD transcriptional activity also dysregulated by loss of ATRX tumor suppressor gene. [28]
 Hippo pathway
  • Subset (~10%) of UPS with amplification of YAP1 and VGLL3. potential for therapeutic intervention. [2] [6]
  • Subset of ATRX-deficient UPS potential therapeutic intervention using TAD domain inhibitors. [23] [24]
TP53, ATRX, RB1
  • Dysregulation principally due to upstream/indirect mechanisms (e.g.epigenetic modulation) rather than direct pathway oncogenic mutations.[30]  
  • TP53, ATRX, RB1 loss indirectly hyperactivates signaling pathways including RAS/MAPK. [30].
 RAS-MAPK (Ras/Raf/MEK/ERK)

Intracellular signaling cascade that transduce extracellular signals from cell surface receptors to nucleus to activate/regulate/drive gene expression in cycle progression. [2] [4]

  • Hyperactivated in >80% of UPS cases. [30].
  • Dysregulation results in unregulated pathway activity, driving tumor growth but also resistance to therapies. [4] [30]
IGF1R, PTEN
  • Dysregulation of pathway components demonstrated, but not direct oncogenic alteration in the majority of UPS. [4].
  • Insulin-like Growth Factor 1 Receptor (1GF1R) heavily implicated in invasive disruption via co-inhibition with pathway. Significantly reducing cell growth, migration, and adaptive resistance. [2] [4]
  • Loss of PTEN gene function, as well as other indirect upstream alterations. [31]
 P13K/mTOR and P13K/AKT,mTOR

Highly conserved signaling pathway cascade acting as a driver, promotes cell growth, survival and cell cycle progression. [2] [4]

  • Most frequently activated signaling pathway; also frequently implicated in therapy resistance. [4] [31]
  • Subset (~20%) of UPS associated with phosphorylation/elevation of downstream marker, PI3K, AKT, and mTOR inhibitors are potential targeted therapeutics. [31]
PD-1, PD-L1, PD-L2
  • Programmed cell death protein 1 is key transmembrane inhibitory receptors on immune cells that binds to distinct ligands PD-L1/PD-L2.  Although different expression and affinity, both inhibit T-cell activation. PD-L2 has more restricted expression and higher affinity. [4] [32]
  • Malfunction is pathogenic, involving upregulation of PD-L1 attenuating the activity of immune cells in tumorigenesis. [4] [32]
 PD-1/PD-L1, PD-1/PD-L2
  • Fundamental mechanism of immune resistance to provide for immune tolerance and prevent immune-mediated tissue destruction. [4] [6] [28]
  • When bound to ligands to form PD-L1 and PD-L2, T-cell activation is inhibited, i.e. halting T-cells killing and reducing T-cell proliferation: serves as a checkpoint to prevent auto immunity. [4] [6] [28]
  • Expression is highly elevated in soft tissue sarcomas including UPS
  • Anti PD-L1/PD-L2 drugs. e.g. Pembrolizumab and Nivolumab, block pathway to restore antitumor immune response.
  • Immune check-point therapy, being evaluated in clinical trials for soft tissue sarcomas including UPS. [4] [6] [28]
  • UPS is rare in pediatrics, most commonly associated with older (50-70yr) age group, with a proportion being immunocompromised due to an underlying CLL. Within this group, a rare subset, PDS, refers to undifferentiated pleomorphic dermal sarcoma. Factors for consideration during evaluation of potential therapeutic options.

Genetic Diagnostic Testing Methods

Because UPS lacks identifiable specific diagnostic characteristics, diagnosis is one of exclusion of other histopathologically comparable sarcomas. Yet UPS exhibits high-grade, high-risk features that demonstrate an aggressive course, high incidence of local recurrence, potential for metastasis and impact overall survival.  Thus any, and all, testing modalities may be considered or used, mainly dependent on institutional genetic knowledgebase and resource availability to eliminate other similar but definable soft tissue sarcomas  

Karyotyping: Highly complex

  • Chromosome number (aneuploidy, individual chromosome(s) trisomy, pentasomy, hexasomy, aneuploidy
  • Structural changes (deletions, telomere association, dicentric chromosomes, unidentifiable markers)
  • Amplification (dmins, homologous staining regions)

Fluorescence in-situ hybridization (FISH): Interphase nuclei analysis

  • Copy number variation (gain or loss) using centromeric or locus specific probes
  • Loss of specific gene regions with locus specific probes such as TP53, CDKN2A, RB1, ATRX

Chromosome Microarray Analysis:  *SNPs

  • CN variation. whole chromosome and region/gene locus specific gain/loss
  • Amplification
  • Chromothripsis
  • *Loss of Heterozygosity (LOH)

Next Generation Sequencing (NGS): Targeted panels

  • Actionable genetic alterations including SNVs, indels, CNVs and fusions within specific cancer- or disease-related genes
  • Comprehensive tumor profiling, identifying driver/recipient alterations related to prognosis, resistance and therapy
  • Some panels detect low level minimal residual disease (MRD)

Whole Genome Sequencing (WGS):

  • Comprehensive view of genetic variation that, in cancer, identifies specific actionable alterations within tumor cells
  • Tailors targeted treatment 

RNA expression analysis:

  • Active gene functioning of oncogenes and functional alterations leading to defining cancer subtypes
  • Tumor heterogeneity, tissue of origin, tumor evolution
  • Real-time treatment response, resistance and MRD

Familial Forms

Undifferentiated pleomorphic sarcoma of bone UPS-B rarely presents as a primary tumor.

The majority of UPS-B occur as a secondary neoplasm to bone avascular necrosis further to history of radiation or prosthetic placement or familial/inherited genetic disorder such as:

  • Paget disease (alteration in SQSTM1 (50% familial, 10% sporadic). [33]
  • Diaphyseal medullary stenosis (rare AD, alteration in 9p21 MTAP). [34]

Additional Information

The WHO 5th Edition 2020 describes Undifferentiated pleomorphic sarcoma (UPS) as a neoplasm of bone UPS-B.

Arising from similar primitive mesenchymal embryonic origin whose cells lack a specific line of differentiation, there are two presentations of UPS: bone UPS-B and more commonly UPS-S soft tissue.

Strong similarity:

  • Clinical behavior - high grade, highly aggressive course
  • Pathology - usually histologically indistinguishable, lacking specific markers,
  • Imaging - high grade pleomorphism
  • High metastatic potential

Comparative analysis highlights differences:

  • Location - medullary cavity of long bones
  • Presentation - often painful, history of bone fractures
  • Frequency difference in G1/S checkpoint genes (e.g. homozyogus deletions of CDKN2A, deletions/alterations in RB1). [4] [35]
  • UPS-B typically younger age of onset*, poorer prognosis than UPS-S. [31] . 
  • Due to the positional tumor microenvironment, at genome level, some molecular characteristics may be different

*Sarcomas are very rare (1%) in adults but more prevalent (15-20%) in pediatrics.  The classification of UPS comprises only 3-8% of sarcomas and is primarily a cancer of advanced age.  Even though UPS-B presents at a younger age, it is extremely rare, especially so in pediatrics. [36]

  • An iliac bone/soft tissue mass from a 13yr old male was submitted with a differential diagnosis of OS, MFS, LS, FS, UPHGS.  FISH and microarray analyses demonstrated FISH negative for split signal using SS18, EWSR1 and BCOR probes, but CN gain of x4-10, x3-6 and x2-5 respectively. CMA/SNP demonstrated a highly heterogeneous/complex karyotype including multiple structural and CN gain/loss (including deletion 17p13 TP53), chromothripsis 11 chromosomes/regions (including entire chromosomes 3,17,18,22), LOH 11 chromosomes/regions (including entire chromosome 13) and amplification 6 chromosomes/regions (including 11q22 YAP1 and apoptosis inhibitors BIRC3, BIRC2). [37]37  

Links

References

  1. ↑ 1.0 1.1 1.2 Gusho, Charles A.; Lee, Linus; Guntin, Jonathan; Blank, Alan T. (2022-02). "Comparison of Features and Outcomes of Undifferentiated Pleomorphic Sarcoma of Bone and Soft Tissue". The Journal of Surgical Research. 270: 313–320. doi:10.1016/j.jss.2021.09.032. ISSN 1095-8673. PMID 34731728. {{cite journal}}: Check date values in: |date= (help)
  2. ↑ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 2.12 2.13 2.14 Zheng, Biqiang; Qu, Yueting; Wang, Jian; Shi, Yingqiang; Yan, Wangjun (2019). "Pathogenic and Targetable Genetic Alterations in Resected Recurrent Undifferentiated Pleomorphic Sarcomas Identified by Targeted Next-generation Sequencing". Cancer Genomics & Proteomics. 16 (3): 221–228. doi:10.21873/cgp.20127. ISSN 1790-6245. PMC 6542646. PMID 31018952.
  3. ↑ 3.0 3.1 3.2 3.3 3.4 Menon G, Solis-Ledesma G. Undifferentiated Pleomorphic Sarcoma. 2025 Jun 23. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan–. PMID: 34033374.
  4. ↑ 4.00 4.01 4.02 4.03 4.04 4.05 4.06 4.07 4.08 4.09 4.10 4.11 4.12 4.13 4.14 4.15 4.16 4.17 4.18 4.19 4.20 4.21 4.22 4.23 4.24 4.25 4.26 4.27 4.28 4.29 4.30 4.31 4.32 4.33 Sun, Haitao; Liu, Jilu; Hu, Fangyuan; Xu, Meng; Leng, Ao; Jiang, Feng; Chen, Kefu (2023). "Current research and management of undifferentiated pleomorphic sarcoma/myofibrosarcoma". Frontiers in Genetics. 14: 1109491. doi:10.3389/fgene.2023.1109491. ISSN 1664-8021. PMC 9978151. PMID 36873946.{{cite journal}}: CS1 maint: article number as page number (link) CS1 maint: unflagged free DOI (link)
  5. ↑ 5.0 5.1 5.2 5.3 5.4 5.5 5.6 Delespaul, Lucile; Lesluyes, Tom; Pérot, Gaëlle; Brulard, Céline; Lartigue, Lydia; Baud, Jessica; Lagarde, Pauline; Le Guellec, Sophie; Neuville, Agnès (2017-02-01). "Recurrent TRIO Fusion in Nontranslocation-Related Sarcomas". Clinical Cancer Research: An Official Journal of the American Association for Cancer Research. 23 (3): 857–867. doi:10.1158/1078-0432.CCR-16-0290. ISSN 1557-3265. PMID 27528700.
  6. ↑ 6.00 6.01 6.02 6.03 6.04 6.05 6.06 6.07 6.08 6.09 6.10 6.11 6.12 6.13 6.14 6.15 6.16 6.17 6.18 Hames-Fathi, Shadi; Nottley, Steven W. G.; Pillay, Nischalan (2022-01). "Unravelling undifferentiated soft tissue sarcomas: insights from genomics". Histopathology. 80 (1): 109–121. doi:10.1111/his.14446. ISSN 1365-2559. PMID 34958500. {{cite journal}}: Check date values in: |date= (help)
  7. ↑ 7.0 7.1 7.2 Bai, Chujie; Zhang, Lu; Wang, Yaohui; You, Xia; Ju, Yongzhi; Sun, Tingting; Fan, Zhengfu (2022-10). "A novel TMTC2-NTRK3 fusion in undifferentiated high-grade pleomorphic sarcoma". Journal of Cancer Research and Clinical Oncology. 148 (10): 2933–2937. doi:10.1007/s00432-022-04249-x. ISSN 1432-1335. PMC 11800999. PMID 35933643. {{cite journal}}: Check date values in: |date= (help)
  8. ↑ 8.0 8.1 8.2 Zhou, Ning; Schäfer, Reinhold; Li, Tao; Fang, Meiyu; Liu, Luying (2018-08-22). "A primary undifferentiated pleomorphic sarcoma of the lumbosacral region harboring a LMNA-NTRK1 gene fusion with durable clinical response to crizotinib: a case report". BMC cancer. 18 (1): 842. doi:10.1186/s12885-018-4749-z. ISSN 1471-2407. PMC 6106902. PMID 30134855.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  9. ↑ 9.0 9.1 Yoshimoto, Masato; Yamada, Yuichi; Ishihara, Shin; Kohashi, Kenichi; Toda, Yu; Ito, Yoshihiro; Yamamoto, Hidetaka; Furue, Masutaka; Nakashima, Yasuharu (2020-01). "Comparative Study of Myxofibrosarcoma With Undifferentiated Pleomorphic Sarcoma: Histopathologic and Clinicopathologic Review". The American Journal of Surgical Pathology. 44 (1): 87–97. doi:10.1097/PAS.0000000000001389. ISSN 1532-0979. PMID 31651522. {{cite journal}}: Check date values in: |date= (help)
  10. ↑ Becerikli, Mustafa; Wieczorek, Stefan; Stricker, Ingo; Nambiar, Sandeep; Rittig, Andrea; Epplen, Joerg Thomas; Tannapfel, Andrea; Lehnhardt, Marcus; Steinstraesser, Lars (2014-12). "Numerical and structural chromosomal anomalies in undifferentiated pleomorphic sarcoma". Anticancer Research. 34 (12): 7119–7127. ISSN 1791-7530. PMID 25503139. {{cite journal}}: Check date values in: |date= (help)
  11. ↑ 11.0 11.1 11.2 Le Guellec, Sophie; Chibon, Frédéric; Ouali, Monia; Perot, Gaëlle; Decouvelaere, Anne-Valérie; Robin, Yves-Marie; Larousserie, Frédérique; Terrier, Philippe; Coindre, Jean-Michel (2014-03). "Are peripheral purely undifferentiated pleomorphic sarcomas with MDM2 amplification dedifferentiated liposarcomas?". The American Journal of Surgical Pathology. 38 (3): 293–304. doi:10.1097/PAS.0000000000000131. ISSN 1532-0979. PMID 24525499. {{cite journal}}: Check date values in: |date= (help)
  12. ↑ 12.0 12.1 12.2 12.3 12.4 12.5 12.6 Lesovaya, Ekaterina A.; Fetisov, Timur I.; Bokhyan, Beniamin Yu; Senchenko, Maria A.; Rogozhin, Dmitry V.; Maksimova, Varvara P.; Demko, Anna N.; Belitsky, Gennady A.; Yakubovskaya, Marianna G. (2025-11-10). "Genetic Heterogeneity of Undifferentiated Pleomorphic Sarcoma: Is There Potential for Targeted Therapy?". Cancers. 17 (22): 3613. doi:10.3390/cancers17223613. ISSN 2072-6694. PMC 12651473. PMID 41300979.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  13. ↑ 13.0 13.1 Ma, Jiemin; Groisberg, Roman; Shao, Changxia; Zhong, Wenjun (2024). "Incidence of Undifferentiated Pleomorphic Sarcoma (UPS) in the United States". Sarcoma. 2024: 6735002. doi:10.1155/2024/6735002. ISSN 1357-714X. PMC 11537747. PMID 39502684.{{cite journal}}: CS1 maint: article number as page number (link) CS1 maint: unflagged free DOI (link)
  14. ↑ 14.0 14.1 14.2 14.3 14.4 López, Saioa; Lim, Emilia L.; Horswell, Stuart; Haase, Kerstin; Huebner, Ariana; Dietzen, Michelle; Mourikis, Thanos P.; Watkins, Thomas B. K.; Rowan, Andrew (2020-03). "Interplay between whole-genome doubling and the accumulation of deleterious alterations in cancer evolution". Nature Genetics. 52 (3): 283–293. doi:10.1038/s41588-020-0584-7. ISSN 1546-1718. PMC 7116784. PMID 32139907. {{cite journal}}: Check date values in: |date= (help)
  15. ↑ 15.0 15.1 15.2 15.3 15.4 15.5 15.6 Bowes, Amy L.; Waise, Sara; Lesluyes, Tom; Butters, Thomas; English, Christie; Yan, Haixi; Verfaillie, Annelien; Davies, Christopher; Chen, Jianan (2026-02-28). "Profiling the genomic landscape and evolutionary history of polyploid giant cancer cells in undifferentiated pleomorphic sarcomas". Cancer Letters. 639: 218173. doi:10.1016/j.canlet.2025.218173. ISSN 1872-7980. PMID 41297660.{{cite journal}}: CS1 maint: article number as page number (link)
  16. ↑ 16.0 16.1 16.2 16.3 Orth, Martin F.; Gerke, Julia S.; Knösel, Thomas; Altendorf-Hofmann, Annelore; Musa, Julian; Alba-Rubio, Rebeca; Stein, Stefanie; Hölting, Tilman L. B.; Cidre-Aranaz, Florencia (2019-02-15). "Functional genomics identifies AMPD2 as a new prognostic marker for undifferentiated pleomorphic sarcoma". International Journal of Cancer. 144 (4): 859–867. doi:10.1002/ijc.31903. ISSN 1097-0215. PMID 30267407.
  17. ↑ 17.0 17.1 17.2 17.3 17.4 17.5 Li, George Z.; Okada, Tomoyo; Kim, Young-Mi; Agaram, Narasimhan P.; Sanchez-Vega, Francisco; Shen, Yawei; Tsubokawa, Norifumi; Rios, Jordan; Martin, Axel S. (2020-06-15). "Rb and p53-Deficient Myxofibrosarcoma and Undifferentiated Pleomorphic Sarcoma Require Skp2 for Survival". Cancer Research. 80 (12): 2461–2471. doi:10.1158/0008-5472.CAN-19-1269. ISSN 1538-7445. PMC 7299798. PMID 32161142.
  18. ↑ 18.0 18.1 18.2 Anderson, William J.; Doyle, Leona A. (2021-04). "Updates from the 2020 World Health Organization Classification of Soft Tissue and Bone Tumours". Histopathology. 78 (5): 644–657. doi:10.1111/his.14265. ISSN 1365-2559. PMID 33438273. {{cite journal}}: Check date values in: |date= (help)
  19. ↑ 19.0 19.1 19.2 19.3 19.4 Remiszewski, Piotr; Tysarowski, Andrzej; Seliga, Katarzyna A.; Bobak, Klaudia; Piątkowski, Jakub; Golik, Paweł; Spałek, Mateusz J.; Szumera-Ciećkiewicz, Anna; Wągrodzki, Michał (2025-12-19). "Clinicopathological and genomic profiling in undifferentiated pleomorphic sarcoma: Small series, clear message". Journal of Applied Genetics. doi:10.1007/s13353-025-01036-5. ISSN 2190-3883. PMID 41413689.
  20. ↑ 20.0 20.1 20.2 Shoshani, Ofer; Brunner, Simon F.; Yaeger, Rona; Ly, Peter; Nechemia-Arbely, Yael; Kim, Dong Hyun; Fang, Rongxin; Castillon, Guillaume A.; Yu, Miao (2021-03-04). "Chromothripsis drives the evolution of gene amplification in cancer". Nature. 591 (7848): 137–141. doi:10.1038/s41586-020-03064-z. ISSN 0028-0836. PMC 7933129. PMID 33361815.
  21. ↑ 21.0 21.1 Thoenen, Elizabeth; Curl, Amanda; Iwakuma, Tomoo (2019-10). "TP53 in bone and soft tissue sarcomas". Pharmacology & Therapeutics. 202: 149–164. doi:10.1016/j.pharmthera.2019.06.010. ISSN 1879-016X. PMC 6746598. PMID 31276706. {{cite journal}}: Check date values in: |date= (help)
  22. ↑ 22.0 22.1 Chen, Xiaohua; Zhang, Taotao; Su, Wei; Dou, Zhihui; Zhao, Dapeng; Jin, Xiaodong; Lei, Huiwen; Wang, Jing; Xie, Xiaodong (2022-11-18). "Mutant p53 in cancer: from molecular mechanism to therapeutic modulation". Cell Death & Disease. 13 (11): 974. doi:10.1038/s41419-022-05408-1. ISSN 2041-4889. PMC 9674619. PMID 36400749.
  23. ↑ 23.0 23.1 23.2 23.3 Denu, Ryan Austin; et al. (2024-05-29). “Impact of ATRX loss on survival and immune microenvironment in multiple sarcoma subtypes” Journal of Clinical Oncology. 42 (16): suppl.11511. doi: 10.1200/JCO.2024.42.16_suppl.11511
  24. ↑ 24.0 24.1 24.2 24.3 24.4 Fang, Yan; Barrows, Douglas; Dabas, Yakshi; Carroll, Thomas S.; Singer, Sam; Tap, William D.; Nacev, Benjamin A. (2024-05-22). "ATRX guards against aberrant differentiation in mesenchymal progenitor cells". Nucleic Acids Research. 52 (9): 4950–4968. doi:10.1093/nar/gkae160. ISSN 1362-4962. PMC 11109985. PMID 38477352.
  25. ↑ Cui, Yayan; Han, Liyuan; Shang, Jianfeng; Fang, Wei; Zhao, Meng; Chen, Dong; Liu, Honggang (2022-05). "Primary cardiac undifferentiated pleomorphic sarcoma is associated with TP53 mutation during lack of MDM2 amplification, and targeted sequencing analysis reveals potentially actionable targets". Human Pathology. 123: 113–122. doi:10.1016/j.humpath.2022.02.006. ISSN 1532-8392. PMID 35181378. {{cite journal}}: Check date values in: |date= (help)
  26. ↑ 26.0 26.1 26.2 26.3 Li, Bingcheng; Li, Li; Li, Xiaoying; Wang, Yuanyuan; Xie, Yuwen; Liu, Chunxia; Li, Feng (2015). "Undifferentiated pleomorphic sarcoma with co-existence of KRAS/PIK3CA mutations". International Journal of Clinical and Experimental Pathology. 8 (7): 8563–8567. ISSN 1936-2625. PMC 4555762. PMID 26339434.
  27. ↑ 27.0 27.1 27.2 Zhang, Peng; Huang, Lingling; Ma, Pengwei; Niu, Xiaoying (2022). "Altered Expressions of NF1 and NF1-Related microRNAs as Biomarkers in the Diagnosis of Undifferentiated Pleomorphic Sarcoma". Frontiers in Genetics. 13: 870191. doi:10.3389/fgene.2022.870191. ISSN 1664-8021. PMC 9086456. PMID 35559021.{{cite journal}}: CS1 maint: article number as page number (link) CS1 maint: unflagged free DOI (link)
  28. ↑ 28.0 28.1 28.2 28.3 28.4 28.5 28.6 Eisinger-Mathason, T. S. Karin; Mucaj, Vera; Biju, Kevin M.; Nakazawa, Michael S.; Gohil, Mercy; Cash, Timothy P.; Yoon, Sam S.; Skuli, Nicolas; Park, Kyung Min (2015-06-30). "Deregulation of the Hippo pathway in soft-tissue sarcoma promotes FOXM1 expression and tumorigenesis". Proceedings of the National Academy of Sciences of the United States of America. 112 (26): E3402–3411. doi:10.1073/pnas.1420005112. ISSN 1091-6490. PMC 4491775. PMID 26080399.
  29. ↑ 29.0 29.1 Plouffe, Steven W.; Meng, Zhipeng; Lin, Kimberly C.; Lin, Brian; Hong, Audrey W.; Chun, Justin V.; Guan, Kun-Liang (2016-12-01). "Characterization of Hippo Pathway Components by Gene Inactivation". Molecular Cell. 64 (5): 993–1008. doi:10.1016/j.molcel.2016.10.034. ISSN 1097-4164. PMC 5137798. PMID 27912098.
  30. ↑ 30.0 30.1 30.2 30.3 Serrano C, Romagosa C, Hernández-Losa J, Simonetti S, Valverde C, Moliné T, Somoza R, Pérez M, Vélez R, Vergés R, Domínguez R, Carles J, Ramón Y Cajal S. RAS/MAPK pathway hyperactivation determines poor prognosis in undifferentiated pleomorphic sarcomas. Cancer. 2016 Jan 1;122(1):99-107. doi: 10.1002/cncr.29733. Epub 2015 Oct 19. PMID: 26479291.
  31. ↑ 31.0 31.1 31.2 31.3 Glaviano, Antonino; Foo, Aaron S. C.; Lam, Hiu Y.; Yap, Kenneth C. H.; Jacot, William; Jones, Robert H.; Eng, Huiyan; Nair, Madhumathy G.; Makvandi, Pooyan (2023-08-18). "PI3K/AKT/mTOR signaling transduction pathway and targeted therapies in cancer". Molecular Cancer. 22 (1): 138. doi:10.1186/s12943-023-01827-6. ISSN 1476-4598. PMC 10436543. PMID 37596643.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  32. ↑ 32.0 32.1 Schöniger, Sandra; Jasani, Bharat (2022-10-04). "The PD-1/PD-L1 Pathway: A Perspective on Comparative Immuno-Oncology". Animals: an open access journal from MDPI. 12 (19): 2661. doi:10.3390/ani12192661. ISSN 2076-2615. PMC 9558501. PMID 36230402.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  33. ↑ Albagha, Omar Me (2015). "Genetics of Paget's disease of bone". BoneKEy Reports. 4: 756. doi:10.1038/bonekey.2015.125. ISSN 2047-6396. PMC 4635861. PMID 26587225.
  34. ↑ Martignetti, J. A.; Desnick, R. J.; Aliprandis, E.; Norton, K. I.; Hardcastle, P.; Nade, S.; Gelb, B. D. (1999-03). "Diaphyseal medullary stenosis with malignant fibrous histiocytoma: a hereditary bone dysplasia/cancer syndrome maps to 9p21-22". American Journal of Human Genetics. 64 (3): 801–807. doi:10.1086/302297. ISSN 0002-9297. PMC 1377798. PMID 10053015. {{cite journal}}: Check date values in: |date= (help)
  35. ↑ Niini, Tarja; Lahti, Leo; Michelacci, Francesca; Ninomiya, Shinsuke; Hattinger, Claudia Maria; Guled, Mohamed; Böhling, Tom; Picci, Piero; Serra, Massimo (2011-05). "Array comparative genomic hybridization reveals frequent alterations of G1/S checkpoint genes in undifferentiated pleomorphic sarcoma of bone". Genes, Chromosomes & Cancer. 50 (5): 291–306. doi:10.1002/gcc.20851. ISSN 1098-2264. PMID 21254299. {{cite journal}}: Check date values in: |date= (help)
  36. ↑ Saoud C, Gundem G, Vanderbilt CM, Wexler LH, Reed DR, Tap W, Singer S, Villafania LB, Papaemmanouil E, Benhamida J, Bale TA, Antonescu CR. Undifferentiated Pleomorphic Sarcoma in Children and Young Adults: A Comprehensive Clinicopathologic, Genomic, and Epigenetic Comparison With Adult Counterparts. Mod Pathol. 2025 Aug;38(8):100769. doi: 10.1016/j.modpat.2025.100769. Epub 2025 Apr 11. PMID: 40222653; PMCID: PMC12353165.
  37. ↑ Sutcliffe, Maxine J.; et al. (2022). "Harnessing the power of microarray in the analysis of rarer pediatric sarcomas". Cancer Genetics. 268-269: suppl.1(8). doi.org.10.1016/jcancergen.2022.30.011

Notes

*Primary authors will typically be those that initially create and complete the content of a page.  If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the Associate Editor or other CCGA representative.  When pages have a major update, the new author will be acknowledged at the beginning of the page, and those who contributed previously will be acknowledged below as a prior author.

Prior Author(s): *Citation of this Page: “Undifferentiated pleomorphic sarcoma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 04/28/2026, https://ccga.io/index.php/STBT5:Undifferentiated pleomorphic sarcoma.

Retrieved from "https://content.ccga.io/index.php?title=STBT5:Undifferentiated_pleomorphic_sarcoma&oldid=21177"