Frequent genomic abnormalities at TWIST in human pediatric osteosarcomas

Abstract

The identification of genes as markers for chromosome aberrations in specific tumors might facilitate oncogenesis mechanism comprehension, cancer detection, prediction of clinical outcomes, and response to therapy. Previous physiologic and oncologic data identified the TWIST gene as a marker for mesodermal derivative and bone tissue differentiation, but its contribution to bone malignancies has not been investigated. In the present study, search for genomic alterations in high-grade pediatric osteosarcomas was focused on the 7p21 region, and more specifically on the TWIST gene. In a cohort of 74 patients, we observed by allelotyping that 31 of 68 informative tumors were rearranged at the TWIST locus. Among them, analysis by quantitative PCR (QPCR) revealed that, surprisingly, mostly deletions (22/68), but also amplifications (9/ 68), of the TWIST gene were detected. Furthermore, deletions at TWIST were statistically correlated to other molecular abnormalities, like alterations at the APC or c-kit loci, as well as to clinical features such as a poor outcome. This work shows that the TWIST gene seemed to be involved in high-grade pediatric osteosarcomas and is a new marker with a possible initial predictive value. ' 2005 Wiley-Liss, Inc.

Frzb, a Secreted Wnt Antagonist, Decreases Growth and Invasiveness of Fibrosarcoma Cells Associated with Inhibition of Met Signaling

“…Given the involvement of Wnt target genes in sarcoma progression (11,32,45) and the pronounced inhibitory effects of Frzb and DNLRP5 on tumorigenesis, invasion, and EMT reported in this study, secreted Wnt antagonists deserve further investigation as a new strategy for treatment of human sarcoma. Importantly, a secreted Wnt antagonist consisting of the CRD of Fz8 fused with human IgG has recently showed potent antitumor efficacy in animal models of teratocarcinoma (46).…”

Anti‐apoptotic role of TWIST and its association with Akt pathway in mediating taxol resistance in nasopharyngeal carcinoma cells

“…15 In addition, increased TWIST expression levels are associated with advance tumour stage and poor prognosis in several types of cancer. 9,[14][15][16] More recently, increased TWIST in cancer cells has been shown to promote metastatic ability of breast cancer in in vivo animal models. 12,13 In osteosarcoma, upregulation of TWIST is found to be a predictor in patients with poor response to chemotherapy.…”

Molecular Reclassification in Pediatric Osteosarcomas at Surgical Resection is a Potential Helpful Prognostic Marker

“…Most of the studies, even in our Lab, were focusing on diagnostic samples to determine really early the chemoresistant osteosarcomas [5][6][7][8][13][14][15][16][17]. Nevertheless, this risk re-stratification is necessary to adapt the treatment but, for instance, was mostly based on clinical features [18][19][20][21].…”

“…DNAs originated from blood, biopsy and tumor samples (10 ng) were amplified by PCR in a total volume of 25 µL using 0.125 µL of Taq polymerase and 4 pmol of both forward and Cy5 labeled reverse primers. PCR was carried out in an Omnigen Hybaid Thermocycler (Hybaid Ldt, Ashford, UK) using the protocols already described in our previous publications [13][14][15][16][17]. The PCR products were analyzed by capillary electrophoresis on ABI PRISM® Genetic Analyzer 3100 (Applied Biosystems, Foster City, CA, USA).…”

“…The data were analyzed with the Genemapper Software (Applied Biosystems). This technique detects two types of rearrangements: a modification of the allele ratio in tumor or biopsy DNA compared to the paired blood DNA, which is described as an allelic imbalance (AI), and the microsatellite instability (MSI), which was not described in the entire French osteosarcoma cohort [13][14][15][16][17]. The AI is the witness of a deletion or an amplification of the targeted locus.…”