hCDC4 variation in osteosarcoma

被引:13
作者
Yan, Taiqiang
Wunder, Jay S.
Gokgoz, Nalan
Seto, Kelly K. Y.
Bell, Robert S.
Andrulis, Irene L.
机构
[1] Univ Toronto, Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada
[2] Univ Toronto, Mt Sinai Hosp, Musculoskeletal Oncol Unit, Toronto, ON M5G 1X5, Canada
[3] Univ Toronto, Dept Surg, Toronto, ON, Canada
[4] Univ Toronto, Inst Med Sci, Toronto, ON, Canada
[5] Univ Toronto, Dept Mol & Med Genet, Toronto, ON, Canada
[6] Univ Toronto, Dept Pathol & Lab Med, Toronto, ON, Canada
基金
加拿大健康研究院;
关键词
D O I
10.1016/j.cancergencyto.2006.04.007
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The hCDC4 gene (also known as Fbw7 or Archipelago) encodes an F-box protein that is responsible for targeting cyclin E for Skp1-cullin-F box protein (SCF) ubiquitination and proteosomal degradation. Disruption of this pathway has been associated with chromosomal instability and aneuploidy in several cancer cell lines and primary tumors. This study aimed to examine whether hCDC4 mutations contribute to aneuploidy in osteosarcoma. We analyzed 147 primary high-grade osteosarcoma specimens and 6 osteosarcoma cell lines. The protein truncation test (PTT) and single-strand conformation polymorphism (SSCP) analysis with subsequent sequencing were performed to detect alterations of the hCDC4 gene. All specimens exhibited the same PTT pattern of normal bands with less intense common bands. Two shifts were detected by SSCP, and subsequent DNA analysis identified one in-frame three-base GAG (424-426) deletion and one silent nucleotide substitution (C1261T). We conclude that somatic hCDC4 mutations are infrequent in osteosarcoma, and are unlikely to play an important role in aneuploidy of this tumor. (c) 2006 Elsevier Inc. All rights reserved.
引用
收藏
页码:138 / 142
页数:5
相关论文
共 20 条
[1]   Chromosomal instability in osteosarcoma and its association with centrosome abnormalities [J].
Al-Romaih, K ;
Bayani, J ;
Vorobyova, J ;
Karaskova, J ;
Park, PC ;
Zielenska, M ;
Squire, JA .
CANCER GENETICS AND CYTOGENETICS, 2003, 144 (02) :91-99
[2]   Aneuploidy and malignancy: an unsolved equation [J].
Dey, P .
JOURNAL OF CLINICAL PATHOLOGY, 2004, 57 (12) :1245-1249
[3]  
Fraizer GC, 2004, INT J ONCOL, V25, P1631
[4]   Aurora kinases, aneuploidy and cancer, a coincidence or a real link? [J].
Giet, R ;
Petretti, C ;
Prigent, C .
TRENDS IN CELL BIOLOGY, 2005, 15 (05) :241-250
[5]   Cyclin E dysregulation and chromosomal instability in endometrial cancer [J].
Hubalek, MM ;
Widschwendter, A ;
Erdel, M ;
Gschwendtner, A ;
Fiegl, HM ;
Müller, HM ;
Goebel, G ;
Mueller-Holzner, E ;
Marth, C ;
Spruck, CH ;
Reed, SI ;
Widschwendter, M .
ONCOGENE, 2004, 23 (23) :4187-4192
[6]   Infrequent mutations of Archipelago (hAGO, hCDC4, Fbw7) in primary ovarian cancer [J].
Kwak, EL ;
Moberg, KH ;
Wahrer, DCR ;
Quinn, JE ;
Gilmore, PM ;
Graham, CA ;
Hariharan, IK ;
Harkin, DP ;
Haber, DA ;
Bell, DW .
GYNECOLOGIC ONCOLOGY, 2005, 98 (01) :124-128
[7]   From spindle checkpoint to cancer [J].
Lengauer, C ;
Wang, ZH .
NATURE GENETICS, 2004, 36 (11) :1144-1145
[8]   Can chromosomal instability initiate tumorigenesis? [J].
Michor, F ;
Iwasa, Y ;
Vogelstein, B ;
Lengauer, C ;
Nowak, MA .
SEMINARS IN CANCER BIOLOGY, 2005, 15 (01) :43-49
[9]   Aneuploidy and cancer [J].
Rajagopalan, H ;
Lengauer, C .
NATURE, 2004, 432 (7015) :338-341
[10]   Inactivation of hCDC4 can cause chromosomal instability [J].
Rajagopalan, H ;
Jallepalli, PV ;
Rago, C ;
Velculescu, VE ;
Kinzler, KW ;
Vogelstein, B ;
Lengauer, C .
NATURE, 2004, 428 (6978) :77-81