An imprinted non-coding genomic cluster at 14q32 defines clinically relevant molecular subtypes in osteosarcoma across multiple independent datasets

Journal of Hematology & Oncology
Katherine E HillDimitrios Spentzos

Abstract

A microRNA (miRNA) collection on the imprinted 14q32 MEG3 region has been associated with outcome in osteosarcoma. We assessed the clinical utility of this miRNA set and their association with methylation status. We integrated coding and non-coding RNA data from three independent annotated clinical osteosarcoma cohorts (n = 65, n = 27, and n = 25) and miRNA and methylation data from one in vitro (19 cell lines) and one clinical (NCI Therapeutically Applicable Research to Generate Effective Treatments (TARGET) osteosarcoma dataset, n = 80) dataset. We used time-dependent receiver operating characteristic (tdROC) analysis to evaluate the clinical value of candidate miRNA profiles and machine learning approaches to compare the coding and non-coding transcriptional programs of high- and low-risk osteosarcoma tumors and high- versus low-aggressiveness cell lines. In the cell line and TARGET datasets, we also studied the methylation patterns of the MEG3 imprinting control region on 14q32 and their association with miRNA expression and tumor aggressiveness. In the tdROC analysis, miRNA sets on 14q32 showed strong discriminatory power for recurrence and survival in the three clinical datasets. High- or low-risk tumor classification was...Continue Reading

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Citations

Feb 13, 2018·Human Molecular Genetics·Samuel LessardGuillaume Lettre
Aug 8, 2019·Clinical Orthopaedics and Related Research·Santiago A Lozano CalderónDimitrios Spentzos
Aug 23, 2019·Wiley Interdisciplinary Reviews. RNA·Shama Prasada KabekkoduKapaettu Satyamoorthy
Oct 27, 2017·Oncotarget·Yuqing HeWeiming He
Aug 30, 2020·Bioinformatics·Marieke L KuijjerKimberly Glass
Jun 10, 2020·Journal of Bioenergetics and Biomembranes·Yuan LiShuaihua Wang
Jul 16, 2020·International Journal of Molecular Sciences·Yu-Shan ChenFeng-Sheng Wang
Mar 12, 2020·Scientific Reports·Christopher E LietzDimitrios Spentzos
Aug 24, 2020·Bone·Filomena de NigrisClaudio Napoli
Apr 29, 2021·Seminars in Cancer Biology·Anup S PathaniaKishore B Challagundla
May 21, 2021·Skeletal Radiology·Matthew D LiConnie Y Chang
Jun 3, 2021·Cancers·David E CohnWan L Lam
Sep 9, 2021·Cancer Research·Camila M Lopes-RamosMarieke L Kuijjer

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Datasets Mentioned

BETA
GSE39040
E-MTAB-1136
GSE36004

Methods Mentioned

BETA
biopsy
MDS
methylation sequencing

Software Mentioned

BRB
SPSS
TargetScan
PUMA
VISTA Enhancer Browser
ArrayTools
TARGET
DICER
tdROC
PANDA

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