Malignant Giant Cell Tumor of Bone With a KRAS G12V Mutation

Donigian, Sara; Whiteway, Susan L.; Hipp, Sean J.; Lybeck, Dustin; Clark, Rebecca O

doi:10.1097/mph.0000000000002112

Cited by 5 publications

(4 citation statements)

References 23 publications

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“…Herein, MAPK signaling pathway alterations were observed in patients with H3F3A wild-type tumors. Consistent with these findings, KRAS G12V was previously detected in malignant GCTB ( 8 ). HRAS mutations were also previously found in two cases of malignant GCTB ( 9 ), indicating the importance of RAS family mutations in the malignant progression of GCTB.…”

Section: Discussionsupporting

confidence: 87%

“…However, some malignant GCTBs have been found to be negative for H3F3A mutations, even though the paired GCTB component has been found positive for H3F3A mutations (5). Other reports suggested that TP53 mutation, KRAS/HRAS mutation, TERT mutation, KDM4B/KDM6A loss, or H3K27me3 loss may be associated with the malignant progression of GCTB (8)(9)(10)(11). However, oncogenic events in H3F3A wild-type malignant GCTB remain unknown.…”

Section: Introductionmentioning

confidence: 99%

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Clinical genomic profiling of malignant giant cell tumor of bone: A retrospective analysis using a real‑world database

Tsuda,

Okajima,

Ishibashi

et al. 2024

Med Int

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Malignant giant cell tumor of bone (GCTB) is identified by the presence of multinucleated giant cells, with an aggressive behavior and a high risk of metastasis, which has not been genetically characterized in detail. H3 histone family member 3A ( H3F3A ) gene mutations are highly recurrent and specific in GCTB. The present study analyzed the clinical information and genomic sequencing data of eight cases of malignant GCTB (out of 384 bone sarcoma samples) using an anonymized genomic database. There were 5 males and 3 females among the cases, with a median age of 33 years at the time of the initial diagnosis. H3F3A G34W and G34L mutations were detected in 3 patients and 1 patient, respectively. In 75% of cases without H3F3A mutation, mitogen-activated protein kinase (MAPK) signaling pathway gene alterations were found (KRAS single nucleotide variant, KRAS amplification, nuclear respiratory factor 1 -BRAF fusion). Moreover, the collagen type I alpha 2 chain -ALK fusion was detected in remaining one case. The most frequent gene alterations were related to cell cycle regulators, including TP53 , RB1 , cyclin-dependent kinase inhibitor 2A/B and cyclin E1 (75%, 6 of 8 cases). On the whole, the present study discovered recurrent MAPK signaling gene alterations or other gene alterations in cases of malignant GCTB. Of note, two fusion genes should be carefully validated following the pathology re-review by sarcoma pathologists. These two fusion genes may be detected in resembling tumors, which contain giant cells, apart from malignant GCTB. The real-world data used herein provide a unique perspective on genomic alterations in clinicopathologically diagnosed malignant GCTB.

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Section: Discussionsupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Clinical genomic profiling of malignant giant cell tumor of bone: A retrospective analysis using a real‑world database

Tsuda,

Okajima,

Ishibashi

et al. 2024

Med Int

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“…26 A recurrence was seen in one femoral case where argon coagulation was also used in the initial intralesional treatment: it recurred after 12 weeks and became malignant and metastasized, necessitating amputation and palliative treatment. 27 One recurrence was also seen among six de novo cases that were treated with curettage including argon beam coagulation and H 2 O 2 , over a mean follow-up of 35 months. 28…”

Section: Argon Cauterizationmentioning

confidence: 87%

Heat treatment for giant cell tumors of bone: A systematic review

Schoutens,

Verspoor

2023

J Orthop Surg (Hong Kong)

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This systematic review evaluates the effects of heat treatments in de novo, residual and recurrent giant cell tumors of bone (GCTB). Studies were eligible for inclusion if one of the following treatments was administered: radiofrequency ablation (RFA), microwave ablation, argon cauterization, electrocauterization and hot liquid treatment. The primary outcome was recurrence. Secondary outcomes were complications, pain, function, and quality of life. Recurrence rates for microwave ablation as an adjuvant to intralesional curettage were 0%, 4% and 10% (3 retrospective single-group studies); for argon cauterization 4%, 8% and 26% (3 cohort studies); electrocauterization 0% to 33% (8 cohort studies); and hot liquid 9.5% and 24% (2 cohort studies). Follow-up was generally ≥24 months. Data on pain, function and quality of life were scarce. Complications included infection and secondary osteoarthritis. Current evidence does not demonstrate or exclude an effect of heat treatments on recurrence in GCTB. Further research should objectify if (subgroups of) patients benefit from these treatments.

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“…The KRAS mutation has been found to be present in a small percentage of primary bladder adenocarcinomas, is associated with the onset and prognosis of bladder cancer and can be used as a biomarker for bladder cancer surveillance and efficacy evaluation (17)(18)(19). Additionally, Donigian et al (20)confirmed that KRAS G12V mutation was present in bone malignant giant cell tumors. Although there are few studies on KRAS mutation-associated MPMNs, and the primary function of KRAS mutations is unclear, we hypothesize that KRAS mutations may be one of the causative factors of four primary tumors in this case, but the precise mechanism needs to be further studied.…”

Section: Discussionmentioning

confidence: 99%

Multiple primary malignant neoplasm: Case report and comprehensive literature review

Tian

Sun

2023

Front. Oncol.

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Multiple primary tumors, especially quadruple primary tumors, are extremely rare clinically, and there is no standard protocol for clinical management. We described a case in which a bone tumor, a malignant bladder tumor, a malignant melanoma, and an intrahepatic cholangiocarcinoma were all original malignancies. The patient is a 79-year-old woman who underwent surgery for a left middle finger bone tumor 45 years ago, as well as surgery for bladder malignancy and postoperative adjuvant chemotherapy 15 years ago, and the precise pathological results and treatment are unclear. One year ago, she underwent amputation of the toe due to a black mass of the right toe and was diagnosed pathologically as a freckled malignant melanoma of the extremity. Prior to postoperative adjuvant systemic medication, PET/CT revealed malignancy in the lateral segment of the left lobe of the liver, and multiple lymphadenopathies in the left parotid gland, hilar hepatic, and retroperitoneal region. Intrahepatic cholangiocarcinoma was found in the liver puncture biopsy’s pathology report. The serum sample’s next-generation sequencing (NGS) revealed a missense mutation, designated P.G12V, in exon 2 of the KRAS gene. Based on patients with malignant melanoma and intrahepatic cholangiocarcinoma, she received 6 cycles of GP (gemcitabine/cisplatin) combined with Camrelizumab systemic therapy, and followed by 3 cycles of Camrelizumab maintenance therapy, the efficacy was evaluated as stable disease (SD) during treatment. When the 4th cycle of Camrelizumab was suggested for maintenance therapy, the efficacy evaluation revealed that the tumor had greatly advanced. The patient refused to continue anti-tumor therapy and passed away from septic shock and multiple organ failure 3 months later. The patient had satisfactory efficacy and lived for a year after being diagnosed with two primary cancers. Despite the rarity of quadruple primary tumors and the lack of a conventional clinical management strategy, we postulate that germline mutations in the KRAS gene may be closely associated with the formation and development of multiple primary tumors. NGS testing is necessary for clinical management, and systemic treatment based on concurrent multiple main tumors is the key to improving prognosis.

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Malignant Giant Cell Tumor of Bone With a KRAS G12V Mutation

Cited by 5 publications

References 23 publications

Clinical genomic profiling of malignant giant cell tumor of bone: A retrospective analysis using a real‑world database

Clinical genomic profiling of malignant giant cell tumor of bone: A retrospective analysis using a real‑world database

Heat treatment for giant cell tumors of bone: A systematic review

Multiple primary malignant neoplasm: Case report and comprehensive literature review

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