Analysis of chromosomal aberrations involving chromosome 1q31→q53 in a DMBA-induced rat fibrosarcoma cell line: amplification and overexpression of <i>Jak2</i>

Abstract

In a study of DMBA-induced rat fibrosarcomas we repeatedly found deletions and/or amplifications in the long arm of rat chromosome 1 (RNO1). Comparative genome hybridization showed that there was amplification involving RNO1q31→q53 in one of the DMBA-induced rat fibrosarcoma tumors (LB31) and a cell culture derived from it. To identify the amplified genes we physically mapped rat genes implicated in cancer and analyzed them for signs of amplification. The genes were selected based on their locations in comparative maps between rat and man. The rat proto-oncogenes Ccnd1, Fgf4, and Fgf3 (HSA11q13.3), were mapped to RNO1q43 by fluorescence in situ hybridization (FISH). The Ems1 gene was mapped by radiation hybrid (RH) mapping to the same rat chromosome region and shown to be situated centromeric to Ccnd1 and Fgf4. In addition, the proto-oncogenes Hras (HSA11p15.5) and Igf1r (HSA15q25→q26) were mapped to RNO1q43 and RNO1q32 by FISH and Omp (HSA11q13.5) was assigned to RNO1q34. PCR probes for the above genes together with PCR probes for the previously mapped rat genes Bax (RNO1q31) and Jak2 (RNO1q51→q53) were analyzed for signs of amplification by Southern blot hybridization. Low copy number increases of the Omp and Jak2 genes were detected in the LB31 cell culture. Dual color FISH analysis of tumor cells confirmed that chromosome regions containing Omp and Jak2 were amplified and were situated in long marker chromosomes showing an aberrant banding pattern. The configuration of the signals in the marker chromosomes suggested that they had arisen by a break-fusion-bridge (BFB) mechanism.

Defining the Sister Rat Mammary Tumor Cell Lines HH-16 cl.2/1 and HH-16.cl.4 as an In Vitro Cell Model for Erbb2

“…Few studies on the cytogenetic characterization of rat cell lines have been performed, particularly using rat or mouse paint probes. However, there have been some reports addressing rat tumor cell lines indicating RNO1 [3] , [29] , [30] , RNO3 [29] , RNO6 [31] and RNO15 [32] , [33] as recurrent and/or relevant chromosomes related to the tumorigenesis/tumor progression in mammary fibrosarcomas, endometrial adenocarcinomas and lung cancer. Also in our study rearrangements in those chromosomes have been identified, as it is the case of the complex rearrangement involving RNO15 ( Figure 4 ), only detected using the combination of varied cytogenetic tools.…”

“…Chemically induced carcinogenesis of the rat mammary gland has been used extensively to investigate breast cancer. In rat models, the carcinogenic compound 7,12-dimethylbenz[a]anthrazene (DMBA) is frequently used to induce tumors, and DMBA-induced rat mammary tumors and sarcomas are useful cancer models [2] , [3] , [4] . Using the evolutionary conservation of gene segments as a guide, animal models, such as the rat, constitute powerful tools to decipher pathways and genes involved in tumorigenesis [4] .…”

Molecular classification of spontaneous endometrial adenocarcinomas in BDII rats

“…Analysis of AI at the Pten locus in the tumor material was performed by allelotyping using a polymorphic intragenic Pten marker (Sjöling et al 2001) as well as four other markers (D1Rat79, D1Rat81, D1Rat169, and D1Rat300), located close to the Pten gene. Primer pair sequences for these markers were obtained from public databases.…”

Cytogenetic Assessment of the Rat Cell Line CLS-ACI-1: An in vitro Cell Model for <b><i>Mycn</i></b> Overexpression

“…However, the few reports addressing this issue indicate the following chromosomes to be relevant for tumor progression in mammary fibrosarcomas, endometrial adenocarcinomas, and lung cancer: RNO1 [Popescu and Greiner, 1999;Walentinsson et al, 2000;Sjoling et al, 2001;Louzada et al, 2012], RNO3 [Popescu and Greiner, 1999;Louzada et al, 2012], RNO6 [Adamovic et al, 2005;Louzada et al, 2012], and RNO15 [Dano et al, 2001;Hamta and Talebbeigy, 2010;Louzada et al, 2012]. The cell line analyzed here, CLS-ACI-1, also presents rearrangements in these chromosomes, detected only due to the combination of the cytogenetic techniques used ( figs.…”