Abstract Chromosome banding analysis of solid tumors
often yields incomplete karyotypes because of the com-
plex rearrangements encountered. The addition of fluores-
cence in situ hybridization (FISH) methods has helped
improve the accuracy of solid tumor cytogenetics, but the
absence of screening qualities from standard FISH ap-
proaches has proved a severe limitation. We describe the
cytogenetic analysis of ten solid tumors using G-banding
followed by cross-species color banding (RxFISH), a FISH-
based screening technique giving a chromosome-specific
banding pattern based on the genomic homologies between
humans and gibbons. The addition of RxFISH analysis in
all cases led to the identification of previously unidenti-
fied intra- as well as interchromosomal rearrangements,
thus giving a much more certain and detailed karyotype.
In two gastric stromal sarcomas, a tumor type for which no
cytogenetic data were hitherto available, numerical chro-
mosomal aberrations dominated, but one of the tumors
also carried an unbalanced 7;17-translocation with the same
breakpoint in chromosome 17 as that seen in endometrial
stromal sarcomas.
Introduction
At the cytogenetic resolution level, the acquired genetic
aberrations of hematologic malignancies have been far
better characterized than those of the more common solid
tumors, the latter making up only 29% of the total data
base (Mitelman 1998). The reasons for this discrepancy
are manifold, but both the technical difficulty of culturing
tumor parenchyma cells and the cytogenetic difficulty of
identifying their often complex chromosomal rearrange-
ments undoubtedly play a major role.
The introduction of fluorescence in situ hybridization
(FISH) techniques signified an important step towards the
solution of at least the second problem. Whereas the origi-
nal FISH approaches were unable to cover the entire ge-
nome in a single experiment and, hence, were of limited
screening value, the more recent comparative genomic
hybridization (CGH) and combinatorial multifluor FISH
provide an unbiased, genome-wide view of all chromo-
somal aberrations present in the neoplastic cells. How-
ever, even these molecular cytogenetic techniques have
principal limitations, in addition to whatever practical
problems their use is associated with in solid tumor cyto-
genetics. CGH, in which differentially labeled tumor DNA
and normal DNA compete for hybridization to normal
metaphase plates (Kallioniemi et al. 1992; Du Manoir et al.
1993), detects quantitatively major copy-number changes
but cannot reveal balanced chromosomal rearrangements.
In addition, cell-to-cell intratumor karyotypic hetero-
geneity, a characteristic feature of many carcinomas
(Gorunova et al. 1995; Heim et al. 1997), cannot be de-
tected by this approach. Combinatorial multicolor FISH,
i.e., spectral karyotyping and multiplex FISH (Schröck et
al. 1996; Speicher et al. 1996), uses a pool of painting
probes, each labeled with a different combination of five
fluorochromes, to classify all 24 human chromosomes
with distinct colors. This is excellent for the discovery of
the chromosomal origin of unidentified markers in tumor
karyotypes, but intrachromosomal rearrangements such as
inversions and small deletions and duplications remain
undetected.
Cross-species color banding is a new FISH technique
utilizing probes from flow-sorted, differentially labeled
gibbon chromosomes (Wienberg et al. 1990; Wienberg
and Stanyon 1995; Müller et al. 1997 a, b, 1998). Because
Francesca Micci · Manuel R. Teixeira ·
Claudia U. Dietrich · Gunnar Sæter ·
Bodil Bjerkehagen · Sverre Heim
Combined RxFISH/G-banding allows refined karyotyping of solid tumors
Hum Genet (1999) 104 : 370–375 © Springer-Verlag 1999
Received: 15 January 1999 / Accepted: 5 March 1999
ORIGINAL INVESTIGATION
F. Micci · C. U. Dietrich · B. Bjerkehagen · S. Heim
Department of Pathology,
The Norwegian Radium Hospital and Institute for Cancer Research,
N-0310 Oslo, Norway
G. Sæter
Department of Oncology,
The Norwegian Radium Hospital and Institute for Cancer Research,
N-0310 Oslo, Norway
M. R. Teixeira · S. Heim ()
Department of Genetics,
The Norwegian Radium Hospital and Institute for Cancer Research,
N-0310 Oslo, Norway
e-mail: sverre.heim@labmed.uio.no,
Tel.: +47-2293470, Fax: +47-22934440