TY - JOUR
T1 - Calcifying fibrous tumor and inflammatory myofibroblastic tumor are epigenetically related
T2 - A comparative genome-wide methylation study
AU - Tomassen, Tess
AU - Koelsche, Christian
AU - de Leng, Wendy W.J.
AU - Kommoss, Felix K.F.
AU - Voijs, Carmen M.A.
AU - Peeters, Ton
AU - van Noesel, Max M.
AU - Creytens, David
AU - van Gorp, Joost M.
AU - Petersen, Iver
AU - Vokuhl, Christian
AU - von Deimling, Andreas
AU - Mentzel, Thomas
AU - Flucke, Uta
N1 - Funding Information:
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Publisher Copyright:
© 2019
Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.
PY - 2019/8/1
Y1 - 2019/8/1
N2 - Based on histological findings, calcifying fibrous tumor (CFT) may be a late (burned out) stage of inflammatory myofibroblastic tumor (IMT). This concept, however, has not been proven by molecular means. Five CFTs were analyzed for IMT-related rearrangements in ALK, ROS1 and RET using fluorescence in situ hybridization (FISH). Additionally, genome-wide methylation patterns were investigated and compared with IMT (n = 7), leiomyoma (n = 7), angioleiomyoma (n = 9), myopericytoma (n = 7) and reactive soft tissue lesions (n = 10) using unsupervised hierarchical cluster analysis and t distributed stochastic neighbor embedding. CFT patients, 4 females and 1 male, had a median age of 20 years ranging from 7 to 43 years. Two patients were younger than 18 years old. The tumors originated in the abdomen (n = 4) and axilla (n = 1). Histologically, all lesions were (multi) nodular and hypocellular consisting of bland looking (myo)fibroblasts embedded in a collagenous matrix with calcifications. FISH analysis brought up negative results for ALK, RET and ROS1 rearrangements. However, genome-wide methylation analysis revealed overlapping methylation patterns of CFT and IMT forming a distinct homogeneous methylation cluster with exception of one case clustering with myopericytoma/angioleiomyoma. In conclusion, DNA methylation profiling supports the concept that CFT and IMT represent both ends of a spectrum of one entity with CFT being the burn out stage of IMT.
AB - Based on histological findings, calcifying fibrous tumor (CFT) may be a late (burned out) stage of inflammatory myofibroblastic tumor (IMT). This concept, however, has not been proven by molecular means. Five CFTs were analyzed for IMT-related rearrangements in ALK, ROS1 and RET using fluorescence in situ hybridization (FISH). Additionally, genome-wide methylation patterns were investigated and compared with IMT (n = 7), leiomyoma (n = 7), angioleiomyoma (n = 9), myopericytoma (n = 7) and reactive soft tissue lesions (n = 10) using unsupervised hierarchical cluster analysis and t distributed stochastic neighbor embedding. CFT patients, 4 females and 1 male, had a median age of 20 years ranging from 7 to 43 years. Two patients were younger than 18 years old. The tumors originated in the abdomen (n = 4) and axilla (n = 1). Histologically, all lesions were (multi) nodular and hypocellular consisting of bland looking (myo)fibroblasts embedded in a collagenous matrix with calcifications. FISH analysis brought up negative results for ALK, RET and ROS1 rearrangements. However, genome-wide methylation analysis revealed overlapping methylation patterns of CFT and IMT forming a distinct homogeneous methylation cluster with exception of one case clustering with myopericytoma/angioleiomyoma. In conclusion, DNA methylation profiling supports the concept that CFT and IMT represent both ends of a spectrum of one entity with CFT being the burn out stage of IMT.
KW - Calcifying fibrous tumor
KW - Fluorescence in situ hybridization
KW - Genome-wide methylation profiling
KW - Inflammatory myofibroblastic tumor
UR - http://www.scopus.com/inward/record.url?scp=85067047346&partnerID=8YFLogxK
U2 - 10.1016/j.anndiagpath.2019.05.013
DO - 10.1016/j.anndiagpath.2019.05.013
M3 - Article
C2 - 31202195
AN - SCOPUS:85067047346
SN - 1092-9134
VL - 41
SP - 102
EP - 105
JO - Annals of Diagnostic Pathology
JF - Annals of Diagnostic Pathology
ER -