Chromosome 3p loss of heterozygosity and reduced expression of H3K36me3 correlate with longer relapse-free survival in sacral conventional chordoma Journal Article

   

Authors:	Zhu, G. G.; Ramirez, D.; Chen, W.; Lu, C.; Wang, L.; Frosina, D.; Jungbluth, A.; Ntiamoah, P.; Nafa, K.; Boland, P. J.; Hameed, M. R.
Article Title:	Chromosome 3p loss of heterozygosity and reduced expression of H3K36me3 correlate with longer relapse-free survival in sacral conventional chordoma
Abstract:	Conventional chordoma is a rare slow-growing malignant tumor of notochordal origin primarily arising at the base of the skull and sacrococcygeal bones. Chordoma may arise from its benign counterpart, benign notochordal cell tumors, and can also undergo dedifferentiation progressing into dedifferentiated chordoma. No study has directly compared the genomic alterations among these tumors comprising a morphologic continuum. Our prior study identified frequent chromosome 3p loss of heterozygosity and minimal deleted regions on chromosome 3 encompassing SETD2, encoding a histone methyltransferase involved in histone H3 lysine 36 trimethylation (H3K36me3). In the present study, we expanded our study to include 65 sacral conventional chordoma cases, 3 benign notochordal cell tumor cases, and 2 dedifferentiated chordoma cases using single nucleotide polymorphism (SNP) array, targeted next-generation sequencing analysis, and immunohistochemistry. We performed immunohistochemical analysis of histone, H3K36me3, and investigated whether there is any association between the clinical behavior and recurrent chromosome or aneuploidy or H3K36me3 protein expression. We found that there is increased genomic instability from benign notochordal cell tumor to conventional chordoma to dedifferentiated chordoma. The highly recurrent genomic aberration, chromosome 3p loss of heterozygosity (occurred in 70% of conventional chordomas), is correlated with longer relapse-free survival, but not with overall survival or metastasis-free survival in sacral chordoma. Chordomas demonstrate variable patterns and levels of H3K36me3 expression, and reduced expression of H3K36me3 showed marginally significant correlation with longer relapse-free survival. Copy number alterations in the genes encoding the H3K36me3 methylation transferase complex and demethylase may account for the altered H3K36me3 expression levels. © 2020 Elsevier Inc.
Keywords:	immunohistochemistry; adult; controlled study; protein expression; aged; cancer surgery; primary tumor; major clinical study; overall survival; single nucleotide polymorphism; genetics; cancer radiotherapy; follow up; distant metastasis; epigenetics; histone methyltransferase; genomic instability; histone h3; heterozygosity loss; aneuploidy; chordoma; chromosome 3p; lysine; recurrence free survival; relapse-free survival; high throughput sequencing; metastasis free survival; human; male; female; article; h3k36me3
Journal Title:	Human Pathology
Volume:	104
ISSN:	0046-8177
Publisher:	Elsevier Inc.
Date Published:	2020-10-01
Start Page:	73
End Page:	83
Language:	English
DOI:	10.1016/j.humpath.2020.07.002
PUBMED:	32795465
PROVIDER:	scopus
PMCID:	PMC8366418
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85090248249&doi=10.1016%2fj.humpath.2020.07.002&partnerID=40&md5=fb5c60a1c655f05abbc15791163b1424
Notes:	Article -- Export Date: 1 October 2020 -- Source: Scopus

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