Top

Published in:

01-06-2006 | Case report

Monoallelic deletion of the p53 gene through chromosomal translocation in a small cell osteosarcoma

Authors: Jun Nishio, John D. Gentry, James R. Neff, Marilu Nelson, Wayne Daniels, Deborah Perry, Zoran Gatalica, Julia A. Bridge

Published in: Virchows Archiv | Issue 6/2006

Abstract

Small cell osteosarcoma is a rare bone tumor of high-grade malignancy that most often arises in the metaphysis of long bones in the second decade of life. Cytogenetic and molecular genetic findings in small cell osteosarcoma are poorly defined. Conventional cytogenetic analysis of a small cell osteosarcoma arising in the proximal tibia of a 9-year-old male revealed a diploid chromosomal complement with complex structural rearrangements involving chromosomes 6, 16, and 17. Immunohistochemical assessment of p53 protein expression revealed nuclear p53 immunoreactivity in approximately 15% of the neoplastic cells. Subsequent fluorescence in situ hybridization (FISH) analyses confirmed loss of the p53 gene locus on the derivative chromosome 17 homolog and were negative for amplification of the MDM2, CDK4, c-MYC, HER-2/neu, CCND1, and COPS3 gene loci. To the best of our knowledge, this represents the first demonstration of monoallelic deletion of p53 in small cell osteosarcoma, suggesting that p53 alterations may play an important role in the development of small cell osteosarcoma as well as conventional osteosarcoma.

Baron BW, Anastasi J, Thirman MJ, Furukawa Y, Fears S, Kim DC, Simone F, Birkenbach M, Montag A, Sadhu A, Zeleznik-Le N, McKeithan TW (2002) The human programmed cell death-2 (PDCD2) gene is a target of BCL6 repression: implications for a role of BCL6 in the down-regulation of apoptosis. Proc Natl Acad Sci U S A 99:2860–2865CrossRefPubMed

Biegel JA, Wormer RB, Emanuel BS (1989) Complex karyotypes in a series of pediatric osteosarcomas. Cancer Genet Cytogenet 38:89–100CrossRefPubMed

Boehm AK, Neff JR, Squire JA, Bayani J, Nelson M, Bridge JA (2000) Cytogenetic findings in 36 osteosarcoma specimens and a review of the literature. Pediatr Pathol Mol Med 19:359–376CrossRef

Bridge JA, Nelson M, McComb E, McGuire MH, Rosenthal H, Vergara G, Maale GE, Spanier S, Neff JR (1997) Cytogenetic findings in 73 osteosarcoma specimens and a review of the literature. Cancer Genet Cytogenet 95:74–87CrossRefPubMed

Bridge RS Jr, Bridge JA, Neff JR, Naumann S, Althof P, Bruch LA (2004) Recurrent chromosomal imbalances and structurally abnormal breakpoints within complex karyotypes of malignant peripheral nerve sheath tumour and malignant triton tumour: a cytogenetic and molecular cytogenetic study. J Clin Pathol 57:1172–1178CrossRefPubMed

Chandar N, Billig B, McMaster J, Novak J (1992) Inactivation of p53 gene in human and murine osteosarcoma cells. Br J Cancer 65:208–214PubMed

Diller L, Kassel J, Nelson CE, Gryka MA, Litwak G, Gebhardt M, Bressac B, Ozturk M, Baker SJ, Vogelstein B, Friend SH (1990) p53 functions as a cell cycle control protein in osteosarcomas. Mol Cell Biol 10:5772–5781PubMed

Fletcher CDM, Unni KK, Mertens F (eds) (2002) World Health Organization classification of tumours. Pathology and genetics of tumours of soft tissue and bone. IARC Press, Lyon

Giovannini M, Selleri L, Biegel JA, Scotlandi K, Emanuel BS, Evans GA (1992) Interphase cytogenetics for the detection of the t(11;22)(q24;q12) in small round cell tumors. J Clin Invest 90:1911–1918PubMedCrossRef

10.

Henriksen J, Aagesen TH, Maelandsmo GM, Lothe RA, Myklebost O, Forus A (2003) Amplification and overexpression of COPS3 in osteosarcomas potentially target TP53 for proteasome-mediated degradation. Oncogene 22:5358–5361CrossRefPubMed

11.

Higashino F, Yoshida K, Noumi T, Seiki M, Fujinaga K (1995) Ets-related protein E1A-F can activate three different matrix metalloproteinase gene promoters. Oncogene 10:1461–1463PubMed

12.

ISCN (2005) An international system for human cytogenetic nomenclature. In: Shaffer LG, Tommerup N (eds) Karger, Basel

13.

Knuutila S, Bjorkqvist A-M, Autio K, Tarkkanen M, Wolf M, Monni O, Szymanska J, Larramendy ML, Tapper J, Pere H, El-Rifai W, Hemmer S, Wasenius V-M, Vidgren V, Zhu Y (1998) DNA copy number amplifications in human neoplasms: review of comparative genomic hybridization studies. Am J Pathol 152:1107–1123PubMed

14.

Ladanyi M, Gorlick R (2000) Molecular pathology and molecular pharmacology of osteosarcoma. Pediatr Pathol Mol Med 19:391–413CrossRef

15.

Lonardo F, Ueda T, Huvos AG, Healy J, Ladanyi M (1997) p53 and MDM2 alterations in osteosarcoma: correlation with clinicopathologic features and proliferative rate. Cancer 79:1541–1547CrossRefPubMed

16.

Nakajima H, Sim FH, Bond J, Unni KK (1997) Small cell osteosarcoma of bone. Cancer 79:2095–2106CrossRefPubMed

17.

Naumann S, Krallman PA, Unni KK, Fidler ME, Neff JR, Bridge JA (2002) Translocation der(13;21)(q10;q10) in skeletal and extraskeletal mesenchymal chondrosarcoma. Mod Pathol 15:572–576CrossRefPubMed

18.

Noguera R, Navarro S, Triche TJ (1990) Translocation (11;22) in small cell osteosarcoma. Cancer Genet Cytogenet 45:121–124CrossRefPubMed

19.

Papai Z, Feja CN, Hanna EN, Sztan M, Olah E, Szendroi M (1997) P53 overexpression as an indicator of overall survival and response to treatment in osteosarcomas. Pathol Oncol Res 3:15–19PubMed

20.

Prasad R, Gu Y, Alder H, Nakamura T, Canaani O, Saito H, Huebner K, Gale RP, Nowell PC, Kuriyama K (1993) Cloning of the ALL-1 fusion partner, the AF-6 gene, involved in acute myeloid leukemias with the t(6;11) chromosome translocation. Cancer Res 53:5624–5628PubMed

21.

Sandberg AA, Bridge JA (2003) Updates on cytogenetics and molecular genetics of bone and soft tissue tumors: osteosarcoma and related tumors. Cancer Genet Cytogenet 145:1–30CrossRefPubMed

22.

Sim FH, Unni KK, Beabout JW, Dahlin DC (1979) Osteosarcoma with small cells simulating Ewing’s tumor. J Bone Joint Surg Am 61:207–215PubMed

23.

Sjogren H, Orndal C, Tingby O, Meis-Kindblom JM, Kindblom L-G, Stenma G (2004) Cytogenetic and spectral karyotype analyses of benign and malignant cartilage tumours. Int J Oncol 24:1385–1391PubMed

24.

Sztan M, Papai Z, van der Looij M, Olah E (1997) Allelic losses from chromosome 17 in human osteosarcomas. Pathol Oncol Res 3:115–120PubMedCrossRef

25.

Tomasetto C, Regnier C, Moog-Lutz C, Mattei MG, Chenard MP, Lidereau R, Basset P, Rio MC (1995) Identification of four novel human genes amplified and overexpressed in breast carcinoma and localized to the q11–q21.3 region of chromosome 17. Genomics 28:367–376CrossRefPubMed

26.

Tsuchiya T, Sekine K, Hinohara S, Namiki T, Nobori T, Kaneko Y (2000) Analysis of the p16INK4, p14ARF, p15, TP53, and MDM2 genes and their prognostic implications in osteosarcoma and Ewing sarcoma. Cancer Genet Cytogenet 120:91–98CrossRefPubMed

27.

van Dartel M, Hulsebos TJM (2004) Amplification and overexpression of genes in 17p11.2–p12 in osteosarcoma. Cancer Genet Cytogenet 153:77–80CrossRefPubMed

28.

Yotov WV, Hamel H, Rivard G-E, Champagne MA, Russo PA, Leclerc J-M, Bernstein ML, Levy E (1999) Amplifications of DNA Primase 1 (PRIM1) in human osteosarcoma. Genes Chromosomes Cancer 26:62–69CrossRefPubMed

Title: Monoallelic deletion of the p53 gene through chromosomal translocation in a small cell osteosarcoma
Authors: Jun Nishio
John D. Gentry
James R. Neff
Marilu Nelson
Wayne Daniels
Deborah Perry
Zoran Gatalica
Julia A. Bridge
Publication date: 01-06-2006
Publisher: Springer-Verlag
Published in: Virchows Archiv / Issue 6/2006
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI: https://doi.org/10.1007/s00428-006-0181-x

At a glance: The STEP trials

Springer Medicine

Monoallelic deletion of the p53 gene through chromosomal translocation in a small cell osteosarcoma

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 6/2006

Personalized medicine and development of targeted therapies: the upcoming challenge for diagnostic molecular pathology. A review

Multifocal kaposiform haemangioendothelioma

Esophageal squamous cell carcinoma with entirely intramural growth pattern

Molecular analysis of the EGFR-RAS-RAF pathway in pancreatic ductal adenocarcinomas: lack of mutations in the BRAF and EGFR genes

Papillary thyroid carcinoma presenting as a solitary soft tissue arm metastasis in an elderly hyperthyroid patient. Case report and review of the literature

Schiffmann R, Rapkiewicz A, Abu-Asab M, Ries M, Askari H, Tsokos M, Quezado M. Pathological findings in a patient with Fabry disease, who died after 2.5 years of enzyme replacement. Virchows Arch. 2005 Nov 29; 1–7