34
EIGIL K,ELDSEN and STEEN K0LVRAA
The chromosomal origin of small supernumerary marker (SMC) or ring
chromosomes are virtually impossible to establish by conventional cytogenetics, as they contain no banding patterns due to their small size. The
incidence ofSMCs has been estimated at 3-4 per 1000 patients with mental
retardation. The phenotypic consequences of SMCs are difficult to predict
especially if the chromosomal origin of the SMCs are unknown. Therefore
various FISH techniques have been developed to identify the chromosomal origin of these markers but without any clue as to their identity, the
use of classic FISH techniques requires the iterative hybridization of chromosome painting probes or possibly the use of reverse painting. In such
cases 24-color karyotyping is both time- and labor-saving as the technique
involves analysis of the entire genome in a single hybridization experiment (Fig. SF). CGH-analysis in conjunction with other FISH techniques
may be an alternative way of identifying such chromosomal abnormalities
or other numerical aberrations for a whole chromosome (Fig. SE). However, if a mosaicism is present in 50% or less of the cells, CGH-analysis may
not be able to identify the presence of such abnormalities.
In research on archival material of, for example brain tumors
and breast cancers, oncogenes and amplicons that are related to certain
types of tumors have been identified by CGH-analysis (Du Manoir et al.
1993, Nishizaki et al. 1997). These findings may turn out to be important
genetic markers for an estimation of prognosis and stratification of
therapy.
In oncology, it is often difficult to ascertain the chromosomal make-up
of a tumor by conventional banding methods even where dependable metaphases can be obtained, since the chromosomes often exhibits a poor
banding pattern. In spite of this, particular chromosome abnormalities,
especially translocations, characteristic for certain types of solid tumors
or leukemias, have been established by banding methods and more recently in combination with FISH. Such specific alterations have in
some cases correlated with deregulation of translocated genes (Iida et
al. 1997) and in other cases new fusion genes are formed (Rubin et al.
1988). The Philadelphia-chromosome in CML represents such a new fusion gene and was the first specific chromosomal rearrangement related to
a specific type of leukemia (Nowell and Hungerford 1960). Since then tumor specific non-random chromosome aberrations have been identified.
In as many as 80% of the cases, a complete karyotype cannot be established by conventional banding methods even when combined with classic
FISH techniques. By including 24-color karyotyping in the analysis, most
of these cases can now be characterized (Schrock et al. 1996, Speicher et al.
1996, Veldman et al. 1997, Kerndrup & Kjeldsen 2001) which in turn may
EIGIL K,ELDSEN and STEEN K0LVRAA
The chromosomal origin of small supernumerary marker (SMC) or ring
chromosomes are virtually impossible to establish by conventional cytogenetics, as they contain no banding patterns due to their small size. The
incidence ofSMCs has been estimated at 3-4 per 1000 patients with mental
retardation. The phenotypic consequences of SMCs are difficult to predict
especially if the chromosomal origin of the SMCs are unknown. Therefore
various FISH techniques have been developed to identify the chromosomal origin of these markers but without any clue as to their identity, the
use of classic FISH techniques requires the iterative hybridization of chromosome painting probes or possibly the use of reverse painting. In such
cases 24-color karyotyping is both time- and labor-saving as the technique
involves analysis of the entire genome in a single hybridization experiment (Fig. SF). CGH-analysis in conjunction with other FISH techniques
may be an alternative way of identifying such chromosomal abnormalities
or other numerical aberrations for a whole chromosome (Fig. SE). However, if a mosaicism is present in 50% or less of the cells, CGH-analysis may
not be able to identify the presence of such abnormalities.
In research on archival material of, for example brain tumors
and breast cancers, oncogenes and amplicons that are related to certain
types of tumors have been identified by CGH-analysis (Du Manoir et al.
1993, Nishizaki et al. 1997). These findings may turn out to be important
genetic markers for an estimation of prognosis and stratification of
therapy.
In oncology, it is often difficult to ascertain the chromosomal make-up
of a tumor by conventional banding methods even where dependable metaphases can be obtained, since the chromosomes often exhibits a poor
banding pattern. In spite of this, particular chromosome abnormalities,
especially translocations, characteristic for certain types of solid tumors
or leukemias, have been established by banding methods and more recently in combination with FISH. Such specific alterations have in
some cases correlated with deregulation of translocated genes (Iida et
al. 1997) and in other cases new fusion genes are formed (Rubin et al.
1988). The Philadelphia-chromosome in CML represents such a new fusion gene and was the first specific chromosomal rearrangement related to
a specific type of leukemia (Nowell and Hungerford 1960). Since then tumor specific non-random chromosome aberrations have been identified.
In as many as 80% of the cases, a complete karyotype cannot be established by conventional banding methods even when combined with classic
FISH techniques. By including 24-color karyotyping in the analysis, most
of these cases can now be characterized (Schrock et al. 1996, Speicher et al.
1996, Veldman et al. 1997, Kerndrup & Kjeldsen 2001) which in turn may