scholarly journals A Unique Case of Bilateral Thalamic High-Grade Glioma in a Pediatric Patient with LI-Fraumeni Syndrome: Case Presentation and Review of the Literature

2021 ◽  
Vol 13 (2) ◽  
pp. 175-183
Author(s):  
Raffaella Messina ◽  
Gerardo Cazzato ◽  
Teresa Perillo ◽  
Vita Stagno ◽  
Valeria Blè ◽  
...  
Keyword(s):  
Pathological Condition ◽  
High Grade Glioma ◽  
Tp53 Gene ◽  
High Grade ◽  
Pediatric Age ◽  
Li Fraumeni Syndrome ◽  
Qualitative Systematic Review ◽  
History Of ◽  
Li Fraumeni ◽  
Mesh Database

Li-Fraumeni syndrome (LFS) is a rare high-penetrance and autosomal-dominant pathological condition caused by the germline mutation of the TP53 gene, predisposing to the development of tumors from pediatric age. We conducted a qualitative systematic review following the ENTREQ (Enhancing Transparency in Reporting the Synthesis of Qualitative Research) framework. A search was made in MEDLINE/Pubmed and MeSH Database using the terms “Li-Fraumeni” AND “pediatric high-grade glioma (HGG)”, identifying six cases of HGGs in pediatric patients with LFS. We added a further case with peculiar features such as no familiar history of LFS, association of embryonal rhabdomyosarcoma and bithalamic HGG, whose immunohistochemical profile was accurately defined by Next Generation Sequencing. Knowledge synthesis and case analysis grounded the discussion about challenges in the management of this pathology in pediatric age.

scholarly journals Pediatric Case of Li–Fraumeni Syndrome in Honduras

2021 ◽  
Vol 2021 ◽  
pp. 1-4
Author(s):  
R. Martínez-Beckerat ◽  
C. Alas-Pineda ◽  
M. Melgar-Gonzales ◽  
B. Mejía-Raudales ◽  
N. Andino-Paz ◽  
...  
Keyword(s):  
Autosomal Dominant ◽  
Tp53 Gene ◽  
Pediatric Case ◽  
Choroid Plexus Tumor ◽  
Li Fraumeni Syndrome ◽  
Left Lateral Ventricle ◽  
Dominant Disease ◽  
History Of ◽  
Li Fraumeni ◽  
Increased Susceptibility

Li–Fraumeni syndrome is an inherited, autosomal dominant disease. It is categorized as a rare disease caused by mutations of the TP53 gene, which causes increased susceptibility of the patients and their children to many types of cancer. Choroid plexus tumor is rare, which occurs in 0.3 cases per 1,000,000 people, of which 40% turn out to be carcinomas. We present a 12-year-old boy with a history of worsening headaches of more than one month, gait disturbance, projectile vomiting, and right hemiparesis. An intraventricular tumor was identified in the occipital of the left lateral ventricle, which turned out to be a TP53-mutant choroidal plexus carcinoma.

scholarly journals EPCO-23. COMPARATIVE TRANSCRIPTOMICS TO IDENTIFY TARGETED THERAPY CANDIDATES IN HIGH GRADE GLIOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii74-ii74
Author(s):  
Kelsey Hundley ◽  
Olena Vaske ◽  
Geoff Lyle ◽  
Katrina Learned ◽  
Holly Beale ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Therapeutic Targets ◽  
High Grade Glioma ◽  
Comparative Transcriptomics ◽  
Potential Candidate ◽  
High Grade ◽  
Illumina Hiseq ◽  
Li Fraumeni Syndrome ◽  
Statistical Framework ◽  
Genomic Characterization

Abstract Genomic characterization is often used for the identification of therapeutic targets in tumors. Recently, comparative transcriptomics has begun to be utilized for this purpose. In this pilot, we compare the transcriptome of a patient with recurrent high grade glioma (HGG) to our cohort to identify potential therapies. We reviewed transcriptomic profiles from patients who had resection of HGG at our institution over the past year as well as the UCSC cancer compendium. Briefly, tumor RNA was extracted from embedded tumor tissue sections with tumor cellularity higher than 20%. RNA libraries were sequenced to obtain approximately 65 million reads on an Illumina HiSeq 4000 System utilizing patterned flow cell technology. The RNA profile of a 24 male with Li-Fraumeni syndrome and recurrent HGG with leptomeningeal spread underwent comparative transcriptomics to identify targets. A Bayesian statistical framework for gene expression outlier detection was used. These comparisons allowed for the identification of genes and pathways that are significantly overexpressed. Our internal HGG cohort consisted of 44 adult patients and was evenly distributed among the 4 HGG Verhaak subtypes. Our patient of interest had druggable outlier expression in HDAC1, STAT1 and STAT2 in comparison to our internal cohort indicating vorinostat and ruxolitinib as potential therapies, respectively. We then compared our patient of interest to 12,747 patients in the cancer compendium and STAT2 expression was high but not an outlier. In comparison to 738 glioma samples, STAT1 and STAT2 were outliers but not HDAC1 again indicating ruxolitinib as a potential targeted therapy. The patient did not have outlier expression in notch transcriptional targets or immune checkpoint biomarkers when compared to all cohorts. In conclusion, comparative Transcriptomics can identify therapeutic targets in a patient with recurrent HGG even in small cohorts. In our pilot, we identified ruxolitinib as a potential candidate to treat leptomeningeal recurrence.

The TP53 gene promoter is not methylated in families suggestive of Li-Fraumeni syndrome with no germline TP53 mutations

2009 ◽  
Vol 193 (1) ◽  
pp. 63-66 ◽  
Author(s):  
Alena Finkova ◽  
Alzbeta Vazna ◽  
Ondrej Hrachovina ◽  
Sarka Bendova ◽  
Kamila Prochazkova ◽  
...  
Keyword(s):  
Gene Promoter ◽  
Tp53 Gene ◽  
Tp53 Mutations ◽  
Li Fraumeni Syndrome ◽  
Li Fraumeni

scholarly journals Li-Fraumeni Syndrome and p53 in 2015: Celebrating their Silver Anniversary

2016 ◽  
Vol 39 (1) ◽  
pp. 37 ◽  
Author(s):  
David Malkin
Keyword(s):  
Wilms Tumor ◽  
Cancer Genetics ◽  
Tp53 Gene ◽  
Pleuropulmonary Blastoma ◽  
Li Fraumeni Syndrome ◽  
Von Hippel Lindau ◽  
Von Hippel Lindau Disease ◽  
Li Fraumeni ◽  
Sick Children ◽  
Risk Of Cancer

In a typical morning in the Cancer Genetics Clinic at The Hospital for Sick Children in Toronto, the following array of patients and families might be seen: a family of three children, all harbouring a mutation of the succinyl dehydrogenase C gene inherited from their father who had had extensive surgery several years ago for a secreting paraganglioma; three families with Li-Fraumeni syndrome, each with at least one child harbouring a TP53 gene mutation conferring a lifetime risk of cancer approaching 100% and currently undergoing surveillance for early tumour detection; two children with Li-Fraumeni syndrome undergoing treatment for cancer – one having had three cancer diagnoses before 19 months of age and the other just completing therapy for metastatic adrenocortical carcinoma at age 3; two children with von Hippel-Lindau disease being monitored for persistent pancreatic neuroendocrine tumors and cerebellar hemangioblastomas, respectively; and one child with Beckwith-Wiedeman syndrome and Wilms tumor and another child completing therapy for a pleuropulmonary blastoma (PPB).

scholarly journals Unique Case Report of a Meningeal Sarcoma Arising during Ongoing Treatment for Progressing Intraparenchymal Glioma

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Richard A. Peterson ◽  
Bhavani Kashyap ◽  
Pamala A. Pawloski ◽  
Anna C. Forsberg ◽  
Leah R. Hanson
Keyword(s):  
Radiation Therapy ◽  
Genetic Predisposition ◽  
Radiation Treatment ◽  
Tumor Resection ◽  
Tp53 Gene ◽  
World Health ◽  
High Grade ◽  
Who Grade ◽  
Li Fraumeni Syndrome ◽  
High Grade Sarcoma

Radiation-induced sarcomas in the brain are extremely rare, usually occur with an average latency of 9 years, and are associated with poor outcomes. Latency periods shorter than 1 year may indicate a genetic predisposition such as Li-Fraumeni syndrome. A 34-year-old man underwent initial tumor resection and radiation therapy for a World Health Organization (WHO) Grade II Astrocytoma. Within 6 months, the tumor recurred as WHO Grade III and was treated with temozolomide and then bevacizumab. Despite the patient’s apparent improving condition, MRI revealed new dural-based lesions 10 months after radiation therapy and identified as high-grade sarcoma. The patient resumed bevacizumab, began NovoTTF treatment for progressing glioma, and ifosfamide/doxorubicin for the sarcoma. Genetic testing revealed no pathogenic mutation in the TP53 gene. Ultimately, treatment was unsuccessful and the patient succumbed to glioma and sarcoma within 2 years of initial diagnosis. This case was unique due to the rapidly progressing glioma and sudden appearance of a high-grade sarcoma. It is unusual to have two separate intracranial primary cancers with each requiring a different chemotherapy regimen. We discuss the difficulty of simultaneously treating with separate chemotherapy regimens. It remains unclear whether the sarcoma was induced by the radiation treatment or a genetic predisposition.

DDRE-14. OPTIMIZING MDM2 INHIBITION FOR THE TREATMENT OF HIGH-GRADE GLIOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi77-vi77
Author(s):  
Veronica Rendo ◽  
Leslie Lupien ◽  
Nicholas Khuu ◽  
Kristine Pelton ◽  
Lara Elcavage ◽  
...  
Keyword(s):  
High Grade Glioma ◽  
Tp53 Gene ◽  
Resistance Mechanisms ◽  
High Grade ◽  
Wild Type ◽  
Tp53 Mutations ◽  
Activating Mutations ◽  
Cycle Arrest ◽  
Transcriptional Changes ◽  
Mdm2 Inhibitor

Abstract A majority of high grade gliomas retain a wild-type TP53 gene and are amenable to strategies for activation of the pathway to inhibit tumor growth. The interaction between p53 and MDM2 has served as target for such strategies currently in clinical trials for glioblastoma. As the effects and resistance mechanisms of MDM2 inhibition (MDM2i) remain poorly understood in glioma, we performed genomic and transcriptomic analyses in patient-derived models to better characterize sensitive tumors and identify putative biomarkers of drug response. Treatment with an MDM2 inhibitor (KRT232/AMG232) impaired the growth of cell lines with wild-type TP53 status, particularly in tumors with amplification of MDM2/4 or PPM1D activating mutations. Treatment with KRT232 upregulated both cell cycle arrest and apoptotic cellular responses, with unique temporal and transcriptional differences correlated with MDM2/4 or PPM1D status. In other tumors resistance to MDM2i is mainly mediated by TP53 mutations, but in a subset of chronic KRT232-treated glioma models we noted lack of TP53 mutations and identified cell state and transcriptional changes as potentially more treatable mediators of resistance.

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