Targeting Bone Tumours with 45S5 Bioactive Glass.

Despite advances in treatment modalities, bone tumour therapies still face significant challenges. Severe side effects of conventional approaches, such as chemo- and radiation therapy, result in poor survival rates and high tumour recurrence rates, which are the most common issues that need to be improved upon. The aim of this study was to evaluate the therapeutic properties of 45S5 bioactive glass (BG) for targeting bone tumours. The viability of the cells derived from osteosarcoma, chondrosarcoma, and giant cell tumours was significantly reduced in the presence of 45S5-BG. In contrast, the viability of non-malignant osteoblast-like cells, chondrocytes, and bone marrow-derived stromal cells was not or only slightly affected. While alterations to the particle surface induced by heat treatment, acid etching, or incubation in a simulated body fluid had only minor effects on cytotoxicity, reducing the particle size or sintering the material significantly improved the cytotoxic effect of 45S5-BG. Further, using a chicken chorioallantoic membrane assay, the co-transplantation of 45S5-BG resulted in a significant reduction in tumour formation in vivo. Given the known positive effects of BGs on bone regeneration, our findings suggest that 45S5-BG holds great potential for the development of new and effective bone tumour therapies, with minimal side effects on non-malignant cells and simultaneous contribution to bone healing.

[Pediatric giant cell tumor of bone: a clinicopathological analysis of 35 cases].

Objective: To investigate the clinicopathological characteristics of giant cell tumor of bone (GCTB) in children. Methods: A total of 35 cases of GCTB diagnosed at Shanghai Sixth People's Hospital Affiliated to Shanghai Jiaotong University School from 2016 to 2023 were collected, and a retrospective analysis of clinicopathological features and imaging findings was conducted. Results: Pediatric GCTB accounted for approximately 4.6% of total GCTB cases during the study period. There were 11 males and 24 females. The onset age ranged from 9 to 18 years (mean age 15 years, median age 16 years), with 8 cases (8/35, 22.9%) experiencing postoperative recurrence. Twenty-eight cases (28/35, 80%) primarily affected long bones, while 7 cases involved small or irregular bones. Imaging revealed osteolytic changes as the predominant feature, with 3 cases exhibited open physis, one of which had the tumor primarily at the diaphysis without crossing the physis. Histologically, pediatric GCTB resembled adult cases, characterized by mononuclear cells and osteoclast-like giant cells. Seven cases with denosumab treatment demonstrated degrees of giant cell disappearance, increased fibrous tissue and reactive bone proliferation in the stroma. One case was diagnosed as pediatric multicentric GCTB, and three cases as pediatric primary malignant GCTB, with malignant transformation into osteosarcoma. In all 35 cases, mutations in the H3F3A gene were identified, comprising 32 cases with H3.3 p.G34W mutations, one case with H3.3 p.G34V mutation, and 2 cases with H3.3 p.G34L mutations. Notably, the former two categories were successfully validated at the protein level through immunohistochemical staining, utilizing highly specific antibodies tailored for these mutation types: H3.3 p.G34W antibody and H3.3 p.G34V antibody. However, immunohistochemical staining was not available for the last category. Conclusions: Pediatric GCTB predominantly affects females and occurs primarily in long bones, mainly around the knee joint, the majority of tumors predominantly arise in the epiphysis and extend into the metaphysis; however, in cases where the epiphyseal plates are still unclosed, the tumors may be restricted to the metaphysis. Detection of H3F3A gene mutation is crucial for the diagnosis and differential diagnosis of pediatric GCTB.

Resolved Chronic Non-Healing Ulcer After Distal Radius Giant Cell Tumor Resection: Nursing Experience and Wound Care.

BACKGROUND Giant cell tumors of bone typically occur in early adulthood, when the growth plate has closed. The distal radius is the second most common location affected, accounting for 10% to 12% of cases. Complications of poor soft tissue healing are rare in the distal radius, owing to its rich blood supply. However, the curettage procedure and use of bone cement and external fixation can affect the local blood supply. CASE REPORT We present a rare case of a 24-year-old woman with no significant medical history who underwent surgery at a local hospital to treat a giant cell tumor of the radius. During postoperative wound dressing changes, a 4×3-cm area of flushed skin color with a small blister and reduced local sensation was found on the dorsal side of the wrist. The skin condition worsened despite treatment at the surgical outpatient clinic, leading to referral to scar specialist outpatient treatment. Examination revealed a well-healed surgical scar on the palmar side of the wrist, but a skin defect with necrotic tissue and tendon exposure on the dorsal side. The diagnosis was postoperative soft tissue necrosis of the skin with a giant cell tumor of the bone. CONCLUSIONS This case report discusses the management of chronic non-healing postoperative wounds in giant cell tumors of the distal radius. It emphasizes the importance of appropriate dressing changes, selecting suitable dressings, nutritional support, and effective nurse-patient communication. The case serves as an example of best practices for managing these types of wounds.

Denosumab combined with en bloc resection and arthrodesis for recurrent grade 3 giant cell tumor of bone in distal radius.

PURPOSE: This study aimed to analyse the clinical outcomes of preoperative adjuvant denosumab therapy (PADT) combined with resection and arthrodesis for recurrent grade 3 giant cell tumor of bone (GCTB) in the distal radius. METHODS: A retrospective study was conducted on twenty-three patients (8 males, 15 females) who were treated with the adjuvant denosumab combined with en bloc resection (EBR) and arthrodesis for biopsy confirmed recurrent Campanacci III giant cell tumor of bone in the distal radius between January 2015 and December 2022. All 23 patients were treated with wrist arthrodesis reconstruction using autogenous free iliac crest bone graft (ICBG), bridging plate and screws. The local control, metastasis and overall survival were evaluated during the follow-up period. Functional outcomes were evaluated using the Disabilities of the Arm, Shoulder and Hand (DASH) score, Musculoskeletal Tumor Society Score (MSTS-87 and MSTS-93), and grip strength in the follow-up period. Additionally, all surgical or denosumab-related complications that occurred were recorded in this study. RESULTS: Twenty-three patients were included in this retrospective study and no patients were lost in the follow-up period. The average patient age was 32.5 ± 10.2 years (range, 19-53 years) and the mean follow-up time was 35.5 ± 18.4 months (range, 13-72 months). The average tumor length was 71.7 ± 8.7 mm (range, 50 to 85 mm) and bone reconstruction length was 78.5 ± 8.5 mm (range, 60 to 90 mm). Four patients (17.4%) had secondary local recurrence after reoperation and two patients had (8.7%) multiple recurrences. One patient (4.3%) was deceased in the last follow-up due to multiple metastases. The estimated 5-year recurrence-free survival rate was 81.3% and 5-year metastasis-free survival rate was 95.7%. The mean union time was 8.5 ± 1.9 (6-12) months and the overall survivorship of the allograft was 82.7% (21/23) at an average 35 month follow-up. The average MSTS-87 and MSTS-93 scores were 27.8 ± 1.6 (range, from 23 to 30) and 91.5 ± 5.0 (range, from 76 to 100), and the average DASH score was 8.9 ± 3.2 (range, from 3 to 15), respectively. The average grip strength was 64.6 ± 15.7% (range, from 30 to 95%) of the uninvolved side. Eight patients (34.7%) had at least one complication in the follow-up time. Two autografts (8.7%) were removed due to local recurrence and bone nonunion, and the average autograft survival time was 32.8 ± 18.5 months (range, 12 to 72 months). CONCLUSIONS: Preoperative adjuvant denosumab therapy (PADT) combined with en bloc resection and arthrodesis is a promising method for the treatment of recurrent Campanacci III GCTB in distal radius with acceptable short-term local control and functional satisfaction. LEVEL OF EVIDENCE: level IV Therapeutic.

The Role of Bone Grafting vs. Bone Cement in the Treatment of Giant Cell Tumor of Bone: A Systematic Review and Meta-Analysis on the Risk of Recurrence in 1,454 Patients.

BACKGROUND: Giant cell tumor of bone (GCTB) presents a challenge in management due to its invasive nature and propensity for local recurrence. While either bone grafting (BG) or bone cement (BC) can be utilized to fill defects after intralesional curettage, the optimal treatment remains contested. The purpose of this study was to examine the impact of defect filling with BC compared with BG on recurrence rates in patients with GCTB following intralesional curettage. METHODS: A random-effects model binary outcome meta-analysis was performed utilizing recurrence rate for the BC and BG groups to evaluate the risk ratio (p < 0.05 considered significant). There were 1,454 patients included. RESULTS: Intralesional curettage with BG had a recurrence risk ratio of 1.68 (95% confidence interval [CI], 1.22-2.31, p = 0.001) when compared with BC. The overall rate of recurrence for GCTB after intralesional curettage with BC was 20.05% vs. 29.74% with BG (95% CI, 0.17-0.23 vs. 0.26-0.33, p < 0.001). CONCLUSION: Intralesional curettage with BC for the treatment of GCTB demonstrated lower recurrence rates than intralesional curettage with BG. However, the rates of recurrence remain substantial for both groups, necessitating careful consideration of the benefits and potential pitfalls associated with BC vs. BG when considering salvage options after recurrences. LEVEL OF EVIDENCE: Level III. See Instructions for Authors for a complete description of levels of evidence.

Combined preoperative denosumab and adjuvant microwave ablation for high-risk giant cell tumor of bone: a retrospective study in a single center.

BACKGROUND: Giant cell tumor of bone (GCTB) is a locally aggressive neoplasm with a high propensity for recurrence following intralesional curettage. The introduction of denosumab, a RANKL inhibitor, has shown potential in facilitating joint-sparing surgery. However, concerns exist regarding its impact on local recurrence rates. This study aimed to evaluate the efficacy and safety of combined preoperative denosumab with adjuvant microwave ablation (MWA) for the treatment of high-risk GCTB. METHODS: We conducted a retrospective review of 19 patients with high-risk GCTB who underwent preoperative denosumab treatment followed by curettage and adjuvant MWA. The primary outcome measure was the local recurrence rate, with secondary outcomes including functional status assessed by the Musculoskeletal Tumor Society (MSTS) score and safety profile of the treatment. RESULTS: In this retrospective analysis, we evaluated the outcomes of 19 patients with high-risk GCTB treated with preoperative denosumab and adjuvant MWA. The median follow-up duration was 33.1 months, 3 patients (15.8%) experienced local recurrence at a median of 21.6 months postoperatively and the local recurrence-free survival was 81.2% at two years. Notably, no patient developed lung metastasis, and all recurrences were successfully managed with repeat curettage and MWA, with a mean MSTS score of 27.3. No patient required joint replacement due to tumor recurrence, resulting in a 100% joint preservation rate. CONCLUSION: The combination of preoperative denosumab and adjuvant MWA is a feasible and effective strategy for the management of high-risk GCTB, providing effective local control with preserved joint function. This approach may offer a surgical alternative for young patients where joint preservation is paramount.

Validity of the Musculoskeletal Tumor Society Score for lower extremity in patients with bone sarcoma or giant cell tumour of bone undergoing bone resection and reconstruction surgery in hip and knee.

BACKGROUND: The Musculoskeletal Tumor Society Score (MSTS) is widely used to evaluate functioning following surgery for bone and soft-tissue sarcoma. However, concerns have been raised about its content validity due to the lack of patient involvement during item development. Additionally, literature reports inconsistent results regarding data quality and structural validity. This study aimed to evaluate content, structural and construct validity of the Danish version of the MSTS for lower extremity (MSTS-LE). METHODS: The study included patients from three complete cohorts (n = 87) with bone sarcoma or giant cell tumour of bone who underwent bone resection and reconstruction surgery in hip and knee. Content validity was evaluated by linking MSTS items to frameworks of functioning, core outcome sets and semi-structured interviews. Data quality, internal consistency and factor analysis were used to assess the underlying structure of the MSTS. Construct validity was based on predefined hypotheses of correlation between the MSTS and concurrent measurements. RESULTS: Content validity analysis revealed concerns regarding the MSTS. The MSTS did not sufficiently cover patient-important functions, the item Emotional acceptance could not be linked to the framework of functioning, the items Pain and Emotional acceptance pertained to domains beyond functioning and items' response options did not match items. A two-factor solution emerged, with the items Pain and Emotional acceptance loading highly on a second factor distinct from functioning. Internal consistency and construct validity showed values below accepted levels. CONCLUSION: The Danish MSTS-LE demonstrated inadequate content validity, internal consistency, and construct validity. In addition, our analyses did not support unidimensionality of the MSTS. Consequently, the MSTS-LE is not a simple reflection of the construct of functioning and the interpretation of a sum score is problematic. Clinicians and researcher should exercise caution when relying solely on MSTS scores for assessing lower extremity function. Alternative outcome measurements of functioning should be considered for the evaluation of postoperative function in this patient group.

Lymphocyte Infiltration Score and Spatial Characteristics Refined the Prognosis and Denosumab Treatment Responsiveness Indicators for Giant Cell Tumor of Bone.

PURPOSE: The prognostic value of lymphocyte infiltration score (LIS) and its nearest neighbor distance to tumor cells (NNDTC) in giant cell tumor of bone (GCTB) is currently not well established. This study aims to characterize LIS and NNDTC and examine their correlation with denosumab treatment responsiveness, clinicopathologic features, and patient prognosis. METHODS: Using multiplexed quantitative immunofluorescence, LIS was evaluated in 253 tumor specimens, whereas NNDTC was computed using HALO software. Subsequently, we analyzed the association of these parameters with patient outcomes (progression-free survival [PFS] and overall survival [OS]), clinicopathologic features, and denosumab treatment responsiveness. RESULTS: Low LIS was indicative of both poor PFS and OS (both P < .001). In addition, LIS was significantly associated with sex (P = .046), Enneking staging (P < .001), Ki-67 expression (P = .007), and denosumab treatment responsiveness (P = .005). Lower CD8+ (tumor interior [TI]) NNDTC, and CD3+ (TI) NNDTC were associated with worse PFS (P = .003 and .038, respectively), whereas lower CD8+ (TI) NNDTC was associated with worse OS (P = .001), but CD8+ (tumor infiltrating margin) NNDTC had the opposite effect (P = .002). Moreover, NNDTC showed a correlation with several clinicopathologic features. Importantly, LIS outperformed Enneking and Campanacci staging systems in predicting the clinical outcomes of GCTB. CONCLUSION: These findings suggest that LIS is a reliable predictive tool for clinically relevant outcomes and response to denosumab therapy in patients with GCTB. These parameters may prove to be useful in guiding prognostic risk stratification and therapeutic optimization for patients.

The Role of Denosumab Treatment in Recurrent Giant Cell Bone Tumor of the Orbit.

Giant cell tumor of the bone (GCTB) is a rare primary bone neoplasm, representing about 5% of all primary bone tumors. Most GCTBs are found in the epiphysis of long bones, with only 2% of GCTBs involving the skull. In recent years, the receptor activator of nuclear factor Kappa ligand monoclonal antibody denosumab has been demonstrated as a promising therapeutic option for GCTB; however, this is an evolving field. We present a case of a 57-year-old female with a rare GCTB in the right orbit and sinuses, originally thought to be an aneurysmal bone cyst. Her symptoms included proptosis, intermittent blurry vision, sinus congestion, and frontal headaches. After excision, the tumor recurred within 18 months. Upon repeat excision, a diagnosis of GCTB was made. The patient started denosumab therapy and had no tumor growth over the ensuing 2 years, with stability of symptoms and clinical signs on follow-up.

The diagnostic and prognostic value of tartrate-resistant acid phosphatase isoform 5b for giant cell tumor of bone.

BACKGROUND: Serum level of tartrate-resistant acid phosphatase 5b (TRACP5b) is an excellent serum marker of bone resorption. In patients with giant cell tumor of bone (GCTB), TRACP5b levels are reportedly elevated. This study investigated whether TRACP5b could be a diagnostic serum marker and be useful for detecting postoperative disease progression for GCTB. METHODS: Cohort 1: We abstracted data from 120 patients with TRACP5b measurements from our database: 49 patients with GCTB and 71 patients non-GCTB. We compared serum TRACP5b values between the GCTB and non-GCTB groups. Cohort 2 included 47 patients with GCTB who had more than 6 months of follow-up and multiple TRACP5b values. For patients with local recurrence, TRACP5b change rate was calculated by comparing the TRACP5b value just before progression (a) with the value at the time of progression (b): Change rate = [(b)-(a)]/(a). In the non-progression group, the change rate was calculated from the two consecutive TRACP5b values, (c) and (d): Change rate =[(c)-(d)]/(c). We compared TRACP5b change rates between the progression and non-progression groups. RESULTS: Cohort 1: The GCTB group had a significantly higher mean TRACP5b value (1756 ± 2021 mU/dL) than the non-GCTB group (415 ± 219 mU/dL) (p < 0.0001). Cohort 2: The mean TRACP5b change rate of the progression group was significantly higher than the non-progression group (8.53 ± 8.52 and 0.24 ± 0.27, respectively; p < 0.0001). CONCLUSION: TRACP5b is a useful diagnostic marker in GCTB. The rate of change in serum TRACP5b values is a highly sensitive marker for predicting local recurrence in GCTB.

Giant cell tumor of femur with single pulmonary metastasis - yet another curative oligometastasis.

ABSTRACT: Giant cell tumor of bone (GCT) is a benign tumor of bone that is known to be locally aggressive rarely metastasizing to distant sites, most commonly to the lungs. The reported pulmonary metastasis incidence is 1 - 9%. We report a case of GCT with solitary pulmonary metastasis who had significant clinical benefit and disease control with sequential application of surgical resection of pulmonary metastasis, local external beam radiation therapy (EBRT), and systemic Denosumab. We wish to highlight that even in metastatic GCT, there is significant clinical benefit in aggressive treatment.

The tumor-stroma ratio in giant cell tumor of bone: associations with the immune microenvironment and responsiveness to denosumab treatment.

BACKGROUND: Currently, there is limited understanding regarding the clinical significance of the tumor-stroma ratio (TSR) in giant cell tumor of bone (GCTB). Hence, we aimed to investigate the distribution of TSR in GCTB and explore its correlation with various clinicopathologic factors, immune microenvironment, survival prognosis, and denosumab treatment responsiveness. METHODS: We conducted a multicenter cohort study comprising 426 GCTB patients treated at four centers. TSR was evaluated on hematoxylin and eosin-stained and immunofluorescent sections of tumor specimens. Immunohistochemistry was performed to assess CD3+, CD4+, CD8+, CD20+, PD-1+, PD-L1+, and FoxP3+ TIL subtypes as well as Ki-67 expression levels in 426 tissue specimens. These parameters were then analyzed for their correlations with patient outcomes [local recurrence-free survival (LRFS) and overall survival (OS)], clinicopathological features, and denosumab treatment responsiveness. RESULTS: Low TSR was significantly associated with poor LRFS and OS in both cohorts. Furthermore, TSR was also correlated with multiple clinicopathological features, TIL subtype expression, and denosumab treatment responsiveness. TSR demonstrated similar predictive capabilities as the conventional Campanacci staging system for predicting patients' LRFS and OS. CONCLUSION: The results of this study provide evidence supporting the use of TSR as a reliable prognostic tool in GCTB and as a predictor of denosumab treatment responsiveness. These findings may aid in developing individualized treatment strategies for GCTB patients in the future.

The effect of preoperative embolization on giant cell tumors of the bone localized in the iliosacral region of the pelvis.

INTRODUCTION: Giant cell tumors of the bone (GCTB) are aggressive neoplasms, with rare occurrences in the posterior pelvis and sacral area. Surgical challenges in this region include the inability to apply a tourniquet and limited cementation post-curettage due to proximity to neurovascular structures, leading to potential complications. This case-control study explores the impact of preoperative embolization on GCTB located in the iliosacral region. METHODS: Five surgeries (January-December 2021) for pelvic GCTB (3 sacrum, 2 posterior ilium) were performed on four patients. Diagnosis was confirmed through preoperative CT-guided biopsies. One surgery involved curettage with PMMA cement filling, while four surgeries had curettage without cavity filling. Preoperative embolization of the tumor feeding vessel occurred approximately 16 h before surgery in two cases. Denosumab treatment was not administered. RESULTS: Tumor volume, assessed by preoperative MRI, was comparable between patients with and without preoperative embolization (p = .14). Surgeries without embolization had a mean intraoperative blood loss of 3250 ml, erythrocyte transfusion volume of 1125 ml, and a mean surgical time of 114.5 min for two surgeries. Surgeries with preoperative embolization showed a mean intraoperative blood loss of 1850 ml, no erythrocyte transfusion requirement, and a mean surgical time of 68 min. CONCLUSION: Curettage of GCTB in the posterior pelvis and sacrum presents challenges, with significant intraoperative blood loss impacting surgical time and transfusion needs. Preoperative embolization may be beneficial in reducing blood loss during surgery in these cases.

Periprosthetic giant cell tumour of the tibia: en bloc resection and megaprosthesis revision.

We present a case detailing the diagnosis and management of a periprosthetic giant cell tumour in a female patient in her 70s, who had undergone total knee arthroplasty (TKA) for primary osteoarthritis in her right knee 7 years prior. The patient reported 4 months of painful weight-bearing. Various imaging modalities, including plain radiographs, CT scans and MRI, revealed a sizeable lytic lesion beneath the TKA prosthesis, along with loosening of the tibial component.Blood tests and analyses of synovial fluid ruled out periprosthetic joint infection, and a biopsy confirmed the diagnosis of a giant cell tumour of the bone. Treatment entailed en bloc resection of the tumour and revision of the TKA using a hinged, oncological-type megaprosthesis. Surgical procedures involved careful resection of the proximal tibia, preservation of vasculature and the creation of a medial gastrocnemius muscle flap. Following surgery, the patient underwent supervised rehabilitation with a functional brace.

Keratin-Positive Giant Cell Tumor of Bone and Soft Tissue With HMGA2::NCOR2 Fusion in Children Under 10 With Response to Imatinib Therapy: A Case Series.

HMGA2::NCOR2 keratin-positive giant cell tumors in children with response to imatinib in an infant.

Tumor de células gigantes esternal: esternectomía total y reconstrucción con barras de titanio más malla de polipropileno / Sternal Giant Cell Tumor: Total Sternectomy and Reconstruction with Titanium Rods Plus Polypropylene Mesh

El tumor de células gigantes (TCG) constituye un tumor óseo benigno relativamente frecuente. Se caracteriza por ser localmente agresivo y el lugar de presentación más frecuente es a nivel del esqueleto axial (fémur distal o tibia proximal). Hasta la actualidad, existen escasos informes de presentaciones atípicas, como a nivel del esternón. En este informe, se presenta el caso de una paciente mujer de 24 años que presenta tumoración indurada a nivel de la región esternal de crecimiento progresivo asociado a dolor. Los hallazgos radiológicos revelan tumoración osteolítica que tiene como origen el cuerpo del esternón y lo compromete casi en su totalidad. Este se proyecta hacia las partes blandas y llega al plano superficial. Debido a la extensión de la enfermedad y al compromiso extenso en el cuerpo del esternón, se realiza la resección del cuerpo y manubrio esternal. El defecto es reconstruido con malla de polipropileno, barras de titanio, parche de epiplón y autoinjerto de piel; se obtiene una adecuada estabilidad de la caja torácica y resultados estéticos favorables. El caso tiene un adecuado manejo oncológico puesto que la resección es completa con márgenes microscópicos libres (resección R0).

Giant cell tumor (GCT) constitutes a relatively common benign bone tumor, characteri-zed by its local aggressiveness. The most frequent site of occurrence is in the axial ske-leton (distal femur or proximal tibia). To date, there have been few reports of atypical presentations, such as at the level of the sternum. In this report, we present the case of a 24-year-old female patient who presented with an indurated mass in the sternal region, progressively growing and associated with pain. Radiological findings revealed an osteolytic mass originating from the body of the sternum, involving almost its entire extent and projecting into the soft tissues, reaching the superficial plane. Due to the extent of the disease and the extensive involvement of the sternal body, resection of the body and manubrium of the sternum was performed. The surgical defect was reconstructed with polypropylene mesh, titanium bars, an omental patch and a skin graft, achieving adequate stability of the thoracic cage and favorable cosmetic results.

H3.3-G34W in giant cell tumor of bone functionally aligns with the exon choice repressor hnRNPA1L2.

RNA processing is an essential post-transcriptional phenomenon that provides the necessary complexity of transcript diversity prior to translation. Aberrations in this process could contribute to tumourigenesis, and we have previously reported increased splicing alterations in giant cell tumor of bone (GCTB), which carries mutations in the histone variant H3.3 encoding glycine 34 substituted for tryptophan (H3.3-G34W). G34W interacts with several splicing factors, most notably the trans-acting splicing factor hnRNPA1L2. To gain a deeper understanding of RNA processing in GCTB and isogenic HeLa cells with H3.3-G34W, we generated RNA-immunoprecipitation sequencing data from hnRNPA1L2 and H3.3-G34W associated RNAs, which showed that 80% overlapped across genic regions and were frequently annotated as E2F transcription factor binding sites. Splicing aberrations in both GCTB and HeLa cells with H3.3-G34W were significantly enriched for known hnRNPA1L2 binding motifs (p value < 0.01). This splicing aberration differed from hnRNPA1L2 knockouts, which showed alterations independent of H3.3-G34W. Of functional significance, hnRNPA1L2 was redistributed to closely match the H3.3 pattern, likely driven by G34W, and to loci not occupied in normal parental cells. Taken together, our data reveal a functional overlap between hnRNPA1L2 and H3.3-G34W with likely significant consequences for RNA processing during GCTB pathogenesis. This provides novel opportunities for therapeutic intervention in future modus operandi.