The Principles of Clinical Cytogenetics - Extra Materials - Springer

444 Jonathan Fletcher
laboratories. This is, in part, because many brain tumors do not grow well in culture, particularly
when the biopsy material is limited in size or in viability. In addition, some of the clinically relevant
cytogenetic aberrations are amenable to evaluation by FISH, which can be performed on frozen or
paraffin-embedded material once the histologic diagnosis has been established. Examples include 1p
and 19q deletions in oligodendroglioma, the presence of which portends a favorable response to
multiagent chemotherapy regimens (194,195). Other FISH response predictors have been identified
in oligodendroglioma; these include amplification of EGFR (epidermal growth factor receptor) at
7p12 and homozygous deletion of CDKN2A at 9p21, which correlate with poor response to chemotherapy
and reduced survival (194). Molecular cytogenetic response predictors will likely be identified
in other brain tumor subtypes. For example, FISH evaluation of EGFR amplification in
glioblastoma multiforme might be useful in identifying patients who will benefit from small molecule
or immunologic therapies that inhibit EGFR (196).
GERM CELL TUMORS
Many germ cell tumors contain a characteristic cytogenetic marker, isochromosome 12p, which is
often found in the context of a moderately complex karyotype, with clonal polysomies and rearrangements
of various other chromosomes (197) (see Fig. 9). The isochromosome 12p is uncommon,
albeit not unprecedented in carcinomas and sarcomas (198). Therefore, demonstration of isochromosome
12p, particularly in any poorly differentiated cancer, should provoke strong suspicion of a germ
cell origin, but should not be taken as de facto evidence of such origin. The diagnostic distinction
between germ cell and non-germ-cell tumors is relevant clinically, because malignant germ cell tumors
often respond well to cisplatin-based (and other) multiagent chemotherapy regimens.
CONCLUSIONS
Most malignant solid tumors have clonal chromosome aberrations that can be identified using
cytogenetic methods. Accordingly, a normal karyotype in a malignant solid tumor usually signifies
overgrowth by non-neoplastic, stromal, cells. Benign tumors, on the other hand, often have normal
karyotypes. Cytogenetic profiles are often diagnostic in sarcomas and in renal cancers but are less
useful in certain other solid tumors, particularly those with extremely complex karyotypes or in which
the cells grow poorly in tissue culture. The major determinants of success in solid-tumor cytogenetics
include: (1) viable starting material, (2) minimal presence of non-neoplastic cells in the cultures, and
(3) culture conditions that support growth of the neoplastic cells. These cell culture hurdles can be
overcome by performing the analyses on fresh, frozen, or paraffin-embedded tumor (e.g., by FISH).
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