Deletion and Translocation Involving Chromosome 3(p14) in Two Tumorigenic Kaposi's Sarcoma Cell Lines
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Journal of the National Cancer Institute
,
Vol. 88, No. 7, April 3, 1996
REPORTS
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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)