Deletion and Translocation Involving Chromosome 3(p14) in Two Tumorigenic Kaposi's Sarcoma Cell Lines

JNCI Journal of the National Cancer Institute, Apr 1996

Background Two neoplastic Kaposi's sarcoma (KS) cell lines, KS Y-1 (derived from a patient with KS associated with acquired immunodeficiency syndrome) and KS SLK (derived from an immunosuppressed patient with a renal transplant and KS or iatrogenic KS), have been shown to have abnormal chromosome constitution and to require no exogenous growth factors. They produce malignant tumors in immunodeficient mice. In contrast, all other cell cultures prepared in the past from KS specimens have been shown to have normal diploid characteristics, are hyperplastic, and depend on cytokines for growth, but they do not produce malignant tumors in immunodeficient mice. Purpose We investigated whether the chromosomal changes that occurred in these KS cell lines were random or nonrandom and if such changes contribute to the pathogenesis of KS. Methods We used the conventional G-banding technique and fluorescence in situ hybridization to identify structural and numerical chromosomal changes in the KS cell lines. Results We demonstrated that both cell lines are aneuploid and have some additional features in common, i.e., loss of copies of chromosomes 14 and 21 and nonrandom translocations and deletions in the short arm of chromosome 3 at region 3p14. These KS cell lines also exhibit loss of heterozygosity of loci at region 3p14-ter. Conclusion This is the first time nonrandom chromosomal alterations have been described in KS neoplastic cells. On the basis of information available on other cancers, the chromosome 3 alterations observed here can be expected to contribute to the neoplastic process in KS. Implications Future research should focus on the identification of cytogenetic markers, thus facilitating generation of specific molecular probes for detecting neoplastic cells early in the disease process. [J Natl Cancer Inst 1996;88:450–5]

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Deletion and Translocation Involving Chromosome 3(p14) in Two Tumorigenic Kaposi's Sarcoma Cell Lines

0 Journal of the National Cancer Institute , Vol. 88, No. 7, April 3, 1996 REPORTS - Background: Two neoplastic Kaposi's sarcoma (KS) cell lines, KS Y-l (derived from a patient with KS associated with acquired immunodeficiency syndrome) and KS SLK (derived from an immunosuppressed patient with a renal transplant and KS or iatrogenic KS), have been shown to have abnormal chromosome constitution and to require no exogenous growth factors. They produce malignant tumors in immunodeficient mice. In contrast, all other cell cultures prepared in the past from KS specimens have been shown to have normal diploid characteristics, are hyperplastic, and depend on cytokines for growth, but they do not produce malignant tumors in immunodeficient mice. Purpose: We investigated whether the chromosomal changes that occurred in these KS cell lines were random or nonrandom and if such changes contribute to the pathogenesis of KS. Methods: We used the conventional G-banding technique and fluorescence in situ hybridization to identify structural and numerical chromosomal changes in the KS cell lines. Results: We demonstrated that both cell lines are aneuploid and have some additional features in common, i.e., loss of copies of chromosomes 14 and 21 and nonrandom translocations and deletions in the short arm of chromosome 3 at region 3pl4. These KS cell lines also exhibit loss of heterozygosity of loci at region 3pl4-ter. Conclusion: This is the first time nonrandom chromosomal alterations have been described in KS neoplastic cells. On the basis of information available on other cancers, the chromosome 3 alterations observed here can be expected to contribute to the neoplastic process in KS. Implications: Future research should focus on the identification of cytogenetic markers, thus facilitating generation of specific molecular probes for detecting neoplastic cells early in the disease process. [J Natl Cancer Inst 1996;88:450-5] Chromosomal alterations play a pivotal role in the pathogenesis of human cancer by affecting two classes of genes that are critical to the initiation and progression of the disease, proto-oncogenes and tumor suppressor genes (7,2). Translocations and inversions can lead to proto-oncogene activation or new oncogenic chimeric genes, whereas deletions or monosomies may remove recessive tumor suppressor genes. Recurrent and specific translocations and inversions have been identified in many hematologic cancers and in solid tumors (particularly sarcomas) (1,3-6). An aggressive form of Kaposi's sarcoma (KS), once considered a mild angioproliferative neoplasia or hyperplasia of elderly men of Mediterranean origin, is emerging in association with infection by human immunodeficiency virus type 1 (HIV-1) (7-77) and is endemic in parts of Africa (72). The major problem in this neoplasia is the lack of any suitable therapy for acquired immunodeficiency syndrome (AIDS)-associated KS; in particular, there is no biological marker known that will aid in early diagnosis of neoplastic KS. Cytogenetic data on KS are limited to a few studies that include the examination of lymphocytes, fibroblasts, and endothelial cells from patients (75) or the analysis of unbanded chromosomes (14). These studies likely represent analyses of reactive hyperplastic cells rather than of neoplastic cells. In searching for chromosomal alterations relevant to the pathogenesis of KS, we decided to study KS-derived, neoplastic cell lines. Only two such cell lines, KS Y-l and KS SLK, have been described to date. The KS Y-l cell line was derived from an AIDS patient with KS. The establishment and the characteristics of these cell lines were described previously (75,76). The KS SLK cell line (77) was derived from a patient with a renal transplant associated with KS (iatrogenic KS). Both cell lines have an abnormal chromosome constitution and produce malignant tumors in immunodeficient mice. Using a conventional G-banding technique and fluorescence in situ hybridization (FISH) with site-specific and wholechromosome painting probes, we investigated whether the chromosomal alterations in these cell lines were random or nonrandom and if these alterations could contribute to the pathogenesis of KS. Materials and Methods Origin of Cell Cultures We examined two KS cell lines, designated KS Y-l and KS SLK. The KS Y-l cell line was established from a pleural effusion of a patient with AIDS-associated KS. It grows independently of exogenous growth factors and induces angiogenesis and malignant tumors in immunodeficient mice (15). The KS SLK cell line was isolated from a KS lesion of the gingiva of an HTV-1 -negative patient who had developed KS after cyclosporine therapy following renal transplantation. The KS developed shortly after the patient had an acute infection with cytomegalovirus. The KS SLK cell line also exhibits growth independent of exogenous growth factors, induces angiogenesis, and is tumorigenic but not metastatic in nude mice (15). Th (...truncated)


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Nicholas C. Popescu, Drazen B. Zimonjic, Sophie Leventon-Kriss, Joseph L. Bryant, Yanto Lunardi-Iskandar, Robert C. Gallo. Deletion and Translocation Involving Chromosome 3(p14) in Two Tumorigenic Kaposi's Sarcoma Cell Lines, JNCI Journal of the National Cancer Institute, 1996, pp. 450-455, 88/7, DOI: 10.1093/jnci/88.7.450