Overexpression of the Wilms' tumor gene WT1 in human bone and soft-tissue sarcomas.
The expression levels of the Wilms' tumor gene WT1 were examined in 36 cases of various types of human bone and soft-tissue sarcomas using quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR). They included 12 malignant fibrous histiocytomas (MFH), 3 malignant peripheral nerve sheath tumors (MPNST), 6 synovial sarcomas (SyS), 4 myxoid liposarcomas (MyLS), one angiosarcoma (AGS), one clear cell sarcoma (CCS), and 9 osteosarcomas (OS). Eleven (92%) of 12 MFH, 2 (67%) of 3 MPNST, all (100%) of 6 SyS, 2 (50%) of 4 MyLS, one AGS, one CCS, and 5 (56%) of 9 OS cases overexpressed WT1 in the range of 1.4 x 10(-3)-3.9 x 10(-1) levels (WT1 expression level in K562 leukemic cells was defined as 1.0). Thus, 28 (78%) out of 36 various types of human bone and soft-tissue sarcomas overexpressed the WT1 gene. Immunohistochemical analysis showed positive staining for WT1 protein in all of 4 cases (one case each of MFH, MyLS, AGS and OS) with WT1 gene overexpression detected by RT-PCR analysis, demonstrating clearly that WT1 was expressed at the protein level in various types of human bone and soft-tissue sarcomas. The direct sequencing analysis of the WT1 genomic DNA showed no mutations in any of 10 exons of the WT1 gene in 8 different sarcoma samples (3 MFH, one SyS, one MyLS, one AGS, and 2 OS). The present study demonstrates that various types of human bone and soft-tissue sarcomas frequently overexpress the wild-type WT1 gene, suggesting an important role of the wild-type WT1 gene in tumorigenesis of various types of human bone and soft-tissue sarcomas.
Ueda
Takafumi
T
Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, Suita, Osaka.
Oji
Yusuke
Y
Naka
Norifumi
N
Nakano
Yoko
Y
Takahashi
Eigo
E
Koga
Satoko
S
Asada
Momotaro
M
Ikeba
Ai
A
Nakatsuka
Shin-ichi
S
Abeno
Sakie
S
Hosen
Naoki
N
Tomita
Yasuhiko
Y
Aozasa
Katsuyuki
K
Tamai
Noriyuki
N
Myoui
Akira
A
Yoshikawa
Hideki
H
Sugiyama
Haruo
H
D000328:Adult; D000368:Aged; D001483:Base Sequence; D001859:Bone Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology; D017931:DNA Primers; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D016162:Genes, Wilms Tumor; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000235:genetics; D008297:Male; D008875:Middle Aged; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012509:Sarcoma / Q000145:classification / Q000235:genetics* / Q000473:pathology; D025721:WT1 Proteins / Q000032:analysis / Q000235:genetics*; D009396:Wilms Tumor / Q000235:genetics
D017931:DNA Primers; D012334:RNA, Neoplasm; D025721:WT1 Proteins