Immunohistochemical study of histone protein 3 modification in pediatric osteosarcoma identifies reduced H3K27me3 as a marker of poor treatment response.

Autor: Sebastian Kondratowski, Danielle Cohen, Rebecca J Deyell, Ash Sandhu, Jonathan W Bush
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: PLoS ONE, Vol 19, Iss 11, p e0309471 (2024)
Druh dokumentu: article
ISSN: 1932-6203
07248199
DOI: 10.1371/journal.pone.0309471
Popis: The most common pediatric primary malignant bone tumor, osteosarcoma, is often described as genetically non-recurrent and heterogeneous. Neoadjuvant chemotherapy is typically followed by resection and assessment of treatment response, which helps inform prognosis. Identifying biomarkers that may impact chemotherapy response and survival could aid in upfront risk stratification and identify patients in highest need of innovative therapies for future clinical trials. Relative to conventional genetics, little is known about osteosarcoma epigenetics. We aimed to characterize the methylation and phosphorylation status in osteosarcoma using histone markers found in primary diagnostic biopsies and their paired metastases. We constructed two tissue microarray sets from 58 primary diagnostic samples and 54 temporally-separated but related metastatic or recurrent samples, with tissue blocks available from 2002-2022. Clinical charts were reviewed for post-therapy necrosis response, presence of metastatic disease or recurrence, and overall survival. We evaluated 6 histone H3 residues using immunohistochemistry, including H3K4me3, H3K9me3, H3K27me2, H3K27me3, H3S10T11phos, and H3S28phos. Tumors were scored with low (
Databáze: Directory of Open Access Journals
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje