Publication: H3F3A G34 mutation DNA sequencing and G34W immunohistochemistry analysis in 366 cases of giant cell tumors of bone and other bone tumors
Authors
Gong, Lihua ; Bui, Marilyn M. ; Zhang, Wen ; Sun, Xiaoqi ; Zhang, Ming ; Yi, Ding
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Publisher
Universidad de Murcia. Departamento de BiologĂa Celular e HistologĂa
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DOI
10.14670/HH-18-264
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info:eu-repo/semantics/article
Description
Abstract
H3F3A mutations and the expression of
glycine 34 to tryptophan (G34W) mutants in giant cell
tumors of bone (GCTBs) and other bone tumors were
detected to compare H3F3A mutation types and the
expression of G34W-mutant protein in order to provide a
theoretical basis for using H3F3A mutations as a
diagnostic and differential-diagnostic tool for GCTBs. A
total of 366 bone tumor cases were investigated. The
cases involved 215 men and 151 women, whose median
age was 29 years (3-84). The cases included GCTB
(n=180), recurrent GCTB (n=19), GCTB with lung
metastasis (n=5), pediatric GCTB (n=15), primary
malignant GCTB (n=5), chondroblastoma (CB, n=61),
chondrosarcoma grade II (n=15), dedifferentiated
chondrosarcoma (n=17), chondromyxoid fibroma (n=9),
aneurysmal bone cyst (n=9), nonossifying fibroma
(n=9), osteosarcoma (n=16), and undifferentiated
sarcoma (n=6). Sanger DNA sequencing analysis was
used to detect H3F3A mutations. Immunohistochemistry
was used to assess the expression of the G34W-mutated
protein in these bone tumors. DNA sequencing results
revealed H3F3A mutations in 95.00% of GCTBs
(171/180), including glycine 34 to tryptophan (G34W,
163/180, 90.56%), glycine 34 to leucine (G34L, 3/180,
1.67%), glycine 34 to valine (G34V, 3/180, 1.67%), and
glycine 34 to arginine (G34R, 2/180, 1.11%). Recurrent
GCTBs mostly had the H3F3A G34W mutation (18/19,
94.74%), and GCTBs with lung metastasis all had the
H3F3A G34W mutation (5/5, 100%). Pediatric GCTBs
had a mutation rate of 93.33% (14/15), including one
case with G34L. Four cases of primary malignant GCTB
showed the H3F3A G34W mutation (4/5, 80.00%), and
the classical GCTB component and malignant
component showed consistent mutation types.
Immunohistochemistry showed that GCTBs harboring
G34W also expressed the mutant protein in tumor cell
nuclei. Furthermore, one case of GCTB and one case of
recurrent GCTB showed positive G34W
immunostaining results despite being negative for the
genetic mutation. Other bone tumors all showed wildtype expression in both DNA sequencing and
immunohistochemistry. Our large-sample DNA
sequencing analysis detected four different forms of
mutations in GCTBs, including three rare mutation
forms. The most common mutation of H3F3A was
G34W, which was in accordance with the expression of
G34W in GCTBs detected by immunohistochemistry.
Although DNA sequencing analysis detected rare
mutation types of H3F3A, false-negative results were
also present due to the small number of cells in the
samples. Detection of the most common (G34W) mutant
protein by immunohistochemistry was more convenient.
Given the high prevalence of these driver mutations, the
detection of H3F3A mutant proteins can assist in the
diagnosis of GCTB and its differential diagnosis from
other bone tumors.
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Citation
Histology and Histopathology, Vol.36, nÂş1, (2021)
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