Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2009

Open Access 01-12-2009 | Research article

Loss of heterozygosity of TRIM3 in malignant gliomas

Authors: Jean-Louis Boulay, Urs Stiefel, Elisabeth Taylor, Béatrice Dolder, Adrian Merlo, Frank Hirth

Published in: BMC Cancer | Issue 1/2009

Login to get access

Abstract

Background

Malignant gliomas are frequent primary brain tumors associated with poor prognosis and very limited response to conventional chemo- and radio-therapies. Besides sharing common growth features with other types of solid tumors, gliomas are highly invasive into adjacent brain tissue, which renders them particularly aggressive and their surgical resection inefficient. Therefore, insights into glioma formation are of fundamental interest in order to provide novel molecular targets for diagnostic purposes and potential anti-cancer drugs. Human Tripartite motif protein 3 (TRIM3) encodes a structural homolog of Drosophila brain tumor (brat) implicated in progenitor cell proliferation control and cancer stem cell suppression. TRIM3 is located within the loss of allelic heterozygosity (LOH) hotspot of chromosome segment 11p15.5, indicating a potential role in tumor suppression. ...

Methods

Here we analyze 70 primary human gliomas of all types and grades and report somatic deletion mapping as well as single nucleotide polymorphism analysis together with quantitative real-time PCR of chromosome segment 11p15.5.

Results

Our analysis identifies LOH in 17 cases (24%) of primary human glioma which defines a common 130 kb-wide interval within the TRIM3 locus as a minimal area of loss. We further detect altered genomic dosage of TRIM3 in two glioma cases with LOH at 11p15.5, indicating homozygous deletions of TRIM3.

Conclusion

Loss of heterozygosity of chromosome segment 11p15.5 in malignant gliomas suggests TRIM3 as a candidate brain tumor suppressor gene.
Appendix
Available only for authorised users
Literature
1.
Merlo A: Genes and pathways driving glioblastomas in humans and murine disease models. Neurosurg Rev. 2003, 26: 145-158.CrossRefPubMed
2.
The Cancer Genome Atlas Research Network: Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature. 2008, 455: 1061-1068.CrossRef
3.
Stupp R, Hegi ME, Gilbert MR, Chakravarti A: Chemoradiotherapy in malignant glioma: Standard of care and future directions. J Clin Oncol. 2007, 25: 4127-4136.CrossRefPubMed
4.
5.
Sanai N, Alvarez-Buylla A, Berger MS: Neural stem cells and origin of gliomas. N Engl J Med. 2005, 353: 811-822.CrossRefPubMed
6.
7.
8.
Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, Henkelman RM, Cusimano MD, Dirks PB: Identification of human brain tumour initiating cells. Nature. 2004, 432: 396-401.CrossRefPubMed
9.
Taylor MD, Poppleton H, Fuller C, Su X, Liu Y, Jensen P, Magdaleno S, Dalton J, Calabrese C, Board J, Macdonald T, Rutka J, Guha A, Gajjar A, Curran T, Gilbertson RJ: Radial glia cells are candidate stem cells of ependymoma. Cancer Cell. 2005, 8: 323-335.CrossRefPubMed
10.
Bao S, Wu Q, McLendon RE, Hao Y, Shi Q, Hjelmeland AB, Dewhirst MW, Bigner DD, Rich JN: Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature. 2006, 444: 756-760.CrossRefPubMed
11.
Arama E, Dickman D, Kinchie Z, Shearn A, Lev Z: Mutations in the beta-propeller domain of the Drosophila brain tumor (brat) protein induce neoplasm in the larval brain. Oncogene. 2000, 19: 3706-3716.CrossRefPubMed
12.
Loop T, Leemans R, Stiefel U, Hermida L, Egger B, Xie F, Primig M, Certa U, Fischbach KF, Reichert H, Hirth F: Transcriptional signature of an adult brain tumor in Drosophila. BMC Genomics. 2004, 5: 24-CrossRefPubMedPubMedCentral
13.
Caussinus E, Gonzalez C: Induction of tumor growth by altered stem-cell asymmetric division in Drosophila melanogaster. Nat Genet. 2005, 37: 1125-1129.CrossRefPubMed
14.
Bello B, Reichert H, Hirth F: The brain tumor gene negatively regulates neural progenitor cell proliferation in the larval central brain of Drosophila. Development. 2006, 133: 2639-2648.CrossRefPubMed
15.
Lee CY, Wilkinson BD, Siegrist SE, Wharton RP, Doe CQ: Brat is a Miranda cargo protein that promotes neuronal differentiation and inhibits neuroblast self-renewal. Dev Cell. 2006, 10: 441-449.CrossRefPubMed
16.
Betschinger J, Mechtler K, Knoblich JA: Asymmetric segregation of the tumor suppressor Brat regulates self-renewal in Drosophila neural stem cells. Cell. 2006, 124: 1241-1253.CrossRefPubMed
17.
Beaucher M, Goodliffe J, Hersperger E, Trunova S, Frydman H, Shearn A: Drosophila brain tumor metastases express both neuronal and glial cell type markers. Dev Biol. 2007, 301: 287-297.CrossRefPubMed
18.
Bowman SK, Rolland V, Betschinger J, Kinsey KA, Emery G, Knoblich JA: The tumor suppressors Brat and Numb regulate transit-amplifying neuroblast lineages in Drosophila. Dev Cell. 2008, 14: 1-12.CrossRef
19.
Caussinus E, Hirth F: Asymmetric cell division in development and cancer. Prog Mol Subcell Biol. 2007, 45: 205-225.CrossRefPubMed
20.
Reymond A, Meroni G, Fantozzi A, Merla G, Cairo S, Luzi L, Riganelli D, Zanaria E, Messali S, Cainarca S, Guffanti A, Minucci S, Pelicci PG, Ballabio A: The tripartite motif family identifies cell compartments. EMBO J. 2001, 20: 2140-2151.CrossRefPubMedPubMedCentral
21.
El-Husseini AE, Fretier P, Vincent SR: Cloning and characterization of a gene (RNF22) encoding a novel brain expressed ring finger protein (BERP) that maps to human chromosome 11p15.5. Genomics. 2001, 71: 363-367.CrossRefPubMed
22.
Frosk P, Weiler T, Nylen E, Sudha T, Greenberg CR, Morgan K, Fujiwara TM, Wrogemann K: Limb-girdle muscular dystrophy type 2H associated with mutation in TRIM32, a putative E3-ubiquitin-ligase gene. Am J Hum Genet. 2002, 70: 663-672.CrossRefPubMedPubMedCentral
23.
Sardiello M, Cairo S, Fontanella B, Ballabio A, Meroni G: Genomic analysis of the TRIM family reveals two groups of genes with distinct evolutionary properties. BMC Evol Biol. 2008, 8: 225-CrossRefPubMedPubMedCentral
24.
Schiebe M, Ohneseit P, Hoffmann W, Meyermann R, Rodemann HP, Bamberg M: Loss of heterozygosity at 11p15 and p53 alterations in malignant gliomas. J Cancer Res Clin Oncol. 2001, 127: 325-328.CrossRefPubMed
25.
Scelfo RA, Schwienbacher C, Veronese A, Gramantieri L, Bolondi L, Querzoli P, Nenci I, Calin GA, Angioni A, Barbanti-Brodano G, Negrini M: Loss of methylation at chromosome 11p15.5 is common in human adult tumors. Oncogene. 2002, 21: 2564-2572.CrossRefPubMed
26.
Lam CT, Tang CM, Lau KW, Lung ML: Loss of heterozygosity on chromosome 11 in esophageal squamous cell carcinomas. Cancer Lett. 2002, 178: 75-81.CrossRefPubMed
27.
Larson PS, Schlechter BL, King CL, Yang Q, Glass CN, Mack C, Pistey R, de Las Morenas A, Rosenberg CL: CDKN1C/p57kip2 is a candidate tumor suppressor gene in human breast cancer. BMC Cancer. 2008, 8: 68-CrossRefPubMedPubMedCentral
28.
El-Husseini AE, Vincent SR: Cloning and characterization of a novel RING finger protein that interacts with class V myosins. J Biol Chem. 1999, 274: 19771-1977.CrossRefPubMed
29.
El-Husseini AE, Kwasnicka D, Yamada T, Hirohashi S, Vincent SR: BERP, a novel ring finger protein, binds to alpha-actinin-4. Biochem Biophys Res Commun. 2000, 267: 906-911.CrossRefPubMed
30.
Van Diepen MT, Spencer GE, van Minnen J, Gouwenberg Y, Bouwman J, Smit AB, van Kesteren RE: The molluscan RING-finger protein L-TRIM is essential for neuronal outgrowth. Mol Cell Neurosci. 2005, 29: 74-81.CrossRefPubMed
31.
Kleihues P, Louis DN, Scheithauer BW, Rorke LB, Reifenberger G, Burger PC, Cavenee WK: The WHO classification of tumors of the nervous system. J Neuropathol Exp Neurol. 2002, 61: 215-225.CrossRefPubMed
32.
Maier D, Comparone D, Taylor E, Zhang Z, Gratzl O, Van Meir EG, Scott RJ, Merlo A: New deletion in low-grade oligodendroglioma at the glioblastoma suppressor locus on chromosome 10q25–26. Oncogene. 1997, 15: 997-1000.CrossRefPubMed
33.
Maier D, Zhang Z, Taylor E, Hamou MF, Gratzl O, Van Meir EG, Scott RJ, Merlo A: Somatic deletion mapping on chromosome 10 and sequence analysis of PTEN/MMAC1 point to the 10q25–26 region as the primary target in low-grade and high-grade gliomas. Oncogene. 1998, 16: 3331-3335.CrossRefPubMed
34.
Labuhn M, Jones G, Speel EJ, Maier D, Zweifel C, Gratzl O, Van Meir EG, Hegi ME, Merlo A: Quantitative real-time PCR does not show selective targeting of p14(ARF) but concomitant inactivation of both p16(INK4A) and p14(ARF) in 105 human primary gliomas. Oncogene. 2001, 20: 1103-1109.CrossRefPubMed
35.
Sonoda Y, Iizuka M, Yasuda J, Makino R, Ono T, Kayama T, Yoshimoto T, Sekiya T: Loss of heterozygosity at 11p15 in malignant glioma. Cancer Res. 1995, 55: 2166-2168.PubMed
36.
Campuzano S, Modolell J: Patterning of the Drosophila nervous system: the achaete-scute gene complex. Trends Genet. 1992, 8: 202-208.CrossRefPubMed
37.
Cairns P, Tokino K, Eby Y, Sidransky D: Homozygous deletions of 9p21 in primary human bladder tumors detected by comparative multiplex polymerase chain reaction. Cancer Res. 1994, 54: 1422-1424.PubMed
38.
39.
Baffa R, Negrini M, Mandes B, Rugge M, Ranzani GN, Hirohashi S, Croce CM: Loss of heterozygosity for chromosome 11 in adenocarcinoma of the stomach. Cancer Res. 1996, 56: 268-272.PubMed
40.
Fults D, Petronio J, Noblett BD, Pedone CA: Chromosome 11p15 deletions in human malignant astrocytomas and primitive neuroectodermal tumors. Genomics. 1992, 14: 799-801.CrossRefPubMed
41.
Hoffmann MJ, Florl AR, Seifert HH, Schulz WA: Multiple mechanisms downregulate CDKN1C in human bladder cancer. Int J Cancer. 2005, 114: 406-413.CrossRefPubMed
42.
Lu KH, Weitzel JN, Kodali S, Welch WR, Berkowitz RS, Mok SC: A novel 4-cM minimally deleted region on chromosome 11p15.1 associated with high grade nonmucinous epithelial ovarian carcinomas. Cancer Res. 1997, 57: 387-90.PubMed
43.
Nakata T, Yoshimoto M, Kasumi F, Akiyama F, Sakamoto G, Nakamura Y, Emi M: Identification of a new commonly deleted region within a 2-cM interval of chromosome 11p11 in breast cancers. Eur J Cancer. 1998, 34: 417-421.CrossRefPubMed
44.
Zhao B, Bepler G: Transcript map and complete genomic sequence for the 310 kb region of minimal allele loss on chromosome segment 11p15.5 in non-small-cell lung cancer. Oncogene. 2001, 20: 8154-8164.CrossRefPubMed
Metadata
Title
Loss of heterozygosity of TRIM3 in malignant gliomas
Authors
Jean-Louis Boulay
Urs Stiefel
Elisabeth Taylor
Béatrice Dolder
Adrian Merlo
Frank Hirth
Publication date
01-12-2009
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2009
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-9-71

Other articles of this Issue 1/2009

BMC Cancer 1/2009 Go to the issue

Research article

Two mechanisms of the enhanced antibody-dependent cellular cytotoxicity (ADCC) efficacy of non-fucosylated therapeutic antibodies in human blood

Research article

Decreased mitochondrial DNA content in blood samples of patients with stage I breast cancer

Research article

Induction of protective and therapeutic anti-pancreatic cancer immunity using a reconstructed MUC1 DNA vaccine

Research article

The Ets dominant repressor En/Erm enhances intestinal epithelial tumorigenesis in ApcMin mice

Research article

The direct effect of Focal Adhesion Kinase (FAK), dominant-negative FAK, FAK-CD and FAK siRNA on gene expression and human MCF-7 breast cancer cell tumorigenesis

Research article

Safety and preliminary efficacy data of a novel Casein Kinase 2 (CK2) peptide inhibitor administered intralesionally at four dose levels in patients with cervical malignancies
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits